Dr Majid E Warkiani is an Associate Professor in the School of Biomedical Engineering at UTS, Sydney, Australia. He received his PhD in Mechanical Engineering from Nanyang Technological University (NTU) under the prestigious SINGA scholarship from A*STAR, and undertook postdoctoral training at Massachusetts Institute of Technology (SMART centre). He is NHMRC-CD fellow and also a member of Institute for Biomedical Materials & Devices (IBMD) and Center for Health Technologies (CHT) at UTS.
Dr Warkiani’s current research activities focus on three key areas of (i) Microfluidics involving the design and development of novel microfluidic systems for particle and cell sorting (e.g., circulating tumor cells, fetal cells & stem cells) for diagnostic and therapeutic applications, (ii) Organ-on-a-chips involving the fabrication and characterisation of novel 3D lab-on-a-chip systems (e.g., Lung-on-a-chip, Tumour-on-a-chip) to model physiological functions of tissues and organs, and (iii) 3D Printing involving the design and development of novel miniaturised systems (e.g., micromixers, micro-cyclones) for basic and applied research.
Can supervise: YES
- Tissue Engineering
- Introduction to BioMEMS
- Engineering Biomedical Polymer
Aboulkheyr Es, H, Zhand, S, Thiery, JP & Warkiani, ME 2020, 'Pirfenidone reduces immune-suppressive capacity of cancer-associated fibroblasts through targeting CCL17 and TNF-beta', Integrative biology : quantitative biosciences from nano to macro, vol. 12, no. 7, pp. 188-197.View/Download from: Publisher's site
© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: email@example.com. Various factors in the tumor microenvironment (TME) regulate the expression of PD-L1 in carcinoma cells. The cancer-associated fibroblasts (CAFs) play a crucial role in regulating and rewiring TME to enhance their immune suppressive function and to favor the invasion of the malignant cells. Tumor progression may be retarded by targeting CAFs in the TME. Various studies highlighted the ability of targeting CAF with pirfenidone (PFD), leading to increased efficacy of chemotherapy. However, its potential for the reduction of immune-suppression capacity of CAFs remains to be elusive. Here, we assessed the effect of PFD on the expression of PD-L1 on CAF cells. Besides migration inhibitory effects of PFD on CAFs, the expression level of PD-L1 reduced in CAFs after treatment with PFD. The downstream analysis of released cytokines from CAFs showed that PFD significantly dropped the secretion of CCL17 and TNF-β, where a positive association between PFD-targeted proteins and PD-L1 was observed. These data suggest that the treatment of CAF within TME through the PFD may reduce the acquisition of CAF-mediated invasive and immune-suppressive capacity of breast carcinoma cells.
Asadniaye Fardjahromi, M, Razmjou, A, Vesey, G, Ejeian, F, Banerjee, B, Chandra Mukhopadhyay, S & Ebrahimi Warkiani, M 2020, 'Mussel inspired ZIF8 microcarriers: a new approach for large-scale production of stem cells', RSC Advances, vol. 10, no. 34, pp. 20118-20128.View/Download from: Publisher's site
© The Royal Society of Chemistry 2020. Metal-organic frameworks (MOFs) have high porosity, large surface area, and tunable functionality and have been widely used for drug loading. The aim of this study was to exploit unique features of zeolitic imidazolate framework-8 (ZIF8) to develop an innovative composite microcarrier (MC) for human mesenchymal stem cells (hMSCs) adhesion and proliferation. ZIF8 MCs were prepared by immobilization of polydopamine/polyethyleneimine (PDA/PEI) and ZIF8 on the surface of polystyrene beads. The chemical properties of MCs such as coating stability and homogeneity were characterized by different techniques such as ATR-FTIR, XRD, EDX, SEM, and contact angle. The prepared MCs were tested using human adipose-derived mesenchymal stem cells (hADSCs) in both static and dynamic conditions, and results were compared to a commercially available MC (Star-Plus), polydopamine coated MCs and amine-functionalized MCs as a control. Results show that PDA/PEI/ZIF8 coated MCs (in short: ZIF8 MCs) provides an excellent biocompatible environment for hADSCs adhesion and growth. In conclusion, ZIF8 MCs represent suitable and low-cost support for hADSCs culture and expansion, which can maximize cell yield and viability while preserving hADSCs multipotency. The present findings have revealed this strategy has the potential for chemical and topographical modification of MCs in tissue engineering applications.
© 2020 Elsevier Inc. Cancer is a heterogeneous disease that requires a multimodal approach to diagnose, manage and treat. A better understanding of the disease biology can lead to identification of novel diagnostic/prognostic biomarkers and the discovery of the novel therapeutics with the goal of improving patient outcomes. Employing advanced technologies can facilitate this, enabling better diagnostic and treatment for cancer patients. In this regard, microfluidic technology has emerged as a promising tool in the studies of cancer, including single cancer cell analysis, modeling angiogenesis and metastasis, drug screening and liquid biopsy. Microfluidic technologies have opened new ways to study tumors in the preclinical and clinical settings. In this chapter, we highlight novel application of this technology in area of fundamental, translational and clinical cancer research.
Bazaz, SR, Amiri, HA, Vasilescu, S, Mehrizi, AA, Jin, D, Miansari, M & Warkiani, ME 2020, 'Obstacle-free planar hybrid micromixer with low pressure drop', MICROFLUIDICS AND NANOFLUIDICS, vol. 24, no. 8.View/Download from: Publisher's site
Bazaz, SR, Mashhadian, A, Ehsani, A, Saha, SC, Kruger, T & Warkiani, ME 2020, 'Computational inertial microfluidics: a review', LAB ON A CHIP, vol. 20, no. 6, pp. 1023-1048.View/Download from: Publisher's site
Changani, Z, Razmjou, A, Taheri-Kafrani, A, Warkiani, ME & Asadnia, M 2020, 'Surface modification of polypropylene membrane for the removal of iodine using polydopamine chemistry', CHEMOSPHERE, vol. 249.View/Download from: Publisher's site
Ghorbani, F, Fathi, F, Aghebati-Maleki, L, Abolhasan, R, Rikhtegar, R, Dolatabadi, JEN, Babaloo, Z, Khalilzadeh, B, Warkiani, ME, Sharifzadeh, Z, Rashidi, M-R & Yousefi, M 2020, 'Kinetic and thermodynamic study of c-Met interaction with single chain fragment variable (scFv) antibodies using phage based surface plasmon resonance.', Eur J Pharm Sci, vol. 150, pp. 105362-105362.View/Download from: Publisher's site
Mesenchymal epithelial transition factor (c-Met) has been recently regarded as an attractive target for the treatment of cancer. Our previous study showed that c-Met-specific single chain fragment variables (scFvs) can be considered as a promising therapy for cancer, however, their molecular interaction with c-Met protein have not been assessed. Accordingly, in the current study we aim to evaluate the kinetic and thermodynamic properties of c-Met interaction with these scFvs as anticancer agents by means of surface plasmon resonance (SPR) technique. Phage-scFvs were immobilized on the 11-mercaptoundecanoic acid gold chips after carboxylic groups activation by N-ethyl-N-(3-diethylaminopropyl) carbodiimide/N-hydroxysuccinimide and, then the c-Met binding to each scFvs (ES1, ES2, and ES3) at different concentrations (ranging from 20 to 665 μM) was explored. Kinetic studies revealed that ES1 has the highest affinity (KD = 3.36 × 10-8) toward its target at 25°C. Calculation of thermodynamic parameters also showed positive values for enthalpy and entropy changes, which was representative of hydrophobic forces between c-Met and ES1. Furthermore, the positive value of Gibbs free energy indicated that c-Met binding to ES1 was enthalpy-driven. Taken together, we concluded that produced ES1 can be applied as promising scFv-based therapy for diagnosis or targeting of c-Met in various cancers.
Hagihghi, R, Razmjou, A, Orooji, Y, Warkiani, ME & Asadnia, M 2020, 'A miniaturized piezoresistive flow sensor for real-time monitoring of intravenous infusion.', Journal of Biomedical Materials Research Part B: Applied Biomaterials, vol. 108, no. 2, pp. 568-576.View/Download from: Publisher's site
Drug overdose (DO) is considered one of the current issues of intravenous (IV) infusion particularly resulting in serious injuries and deaths. Malfunction of infusion pumps is reported as the main cause of the drug overdose. Live monitoring and flow rate calculation by health professionals have been practicing to avoid DO. However, human errors and miscalculations are inevitable. A secondary measurement tool is required to avoid the risk of OD when infusion pump malfunctions cannot be detected immediately. Here, inspired by nature, we developed a real-time monitoring device through which an administrator can review, evaluate, and modify the IV infusion process. Our flow sensor possesses an erected polymer hair cell on a multi-layered silicon base forming from a patterned gold strained gauge layer on a piezoresistive liquid crystal polymer (LCP) membrane. Gold strain gauges on an LCP membrane have been used instead of a piezoresistive silicon membrane as the sensing element. The combination of gold strain gauges and LCP membrane provides better sensitivity than a piezoresistive silicon membrane of the same dimensions and thickness. We also miniaturized our biocompatible sensor such that it can be possible to install it inside the IV tube in contact with the liquid providing an in-suite online flow monitoring. The proposed LCP membrane sensor is compared with two commercially available IV sensors to validate its flow sensing ability. The experimental results demonstrate that the proposed sensor provides a low threshold detection limit of 5 mL/hr, which betters the performance of other commercial sensors at low flow rates.
Hassanzadeh-Barforoushi, A, Warkiani, ME, Gallego-Ortega, D, Liu, G & Barber, T 2020, 'Capillary-assisted microfluidic biosensing platform captures single cell secretion dynamics in nanoliter compartments', BIOSENSORS & BIOELECTRONICS, vol. 155.View/Download from: Publisher's site
Mahmoudi, T, Tazehkand, AP, Pourhassan-Moghaddam, M, Alizadeh-Ghodsi, M, Ding, L, Baradaran, B, Bazaz, SR, Jin, D & Warkiani, ME 2020, 'PCR-free paper-based nanobiosensing platform for visual detection of telomerase activity via gold enhancement', MICROCHEMICAL JOURNAL, vol. 154.View/Download from: Publisher's site
Mahmoudi, Z, Mohammadnejad, J, Razavi Bazaz, S, Abouei Mehrizi, A, Saidijam, M, Dinarvand, R, Ebrahimi Warkiani, M & Soleimani, M 2020, 'Promoted chondrogenesis of hMCSs with controlled release of TGF-β3 via microfluidics synthesized alginate nanogels', Carbohydrate Polymers, pp. 115551-115551.View/Download from: Publisher's site
Mihandoust, A, Bazaz, SR, Maleki-Jirsaraei, N, Alizadeh, M, Taylor, RA & Warkiani, ME 2020, 'High-throughput particle concentration using complex cross-section microchannels', Micromachines, vol. 11, no. 4.View/Download from: Publisher's site
© 2020 by the authors. High throughput particle/cell concentration is crucial for a wide variety of biomedical, clinical, and environmental applications. In this work, we have proposed a passive spiral microfluidic concentrator with a complex cross-sectional shape, i.e., a combination of rectangle and trapezoid, for high separation efficiency and a confinement ratio less than 0.07. Particle focusing in our microfluidic system was observed in a single, tight focusing line, in which higher particle concentration is possible, as compared with simple rectangular or trapezoidal cross-sections with similar flow area. The sharper focusing stems from the confinement of Dean vortices in the trapezoidal region of the complex cross-section. To quantify this effect, we introduce a new parameter, complex focusing number or CFN, which is indicative of the enhancement of inertial focusing of particles in these channels. Three spiral microchannels with various widths of 400 μ m, 500 μ m, and 600 μ m, with the corresponding CFNs of 4.3, 4.5, and 6, respectively, were used. The device with the total width of 600 μ m was shown to have a separation efficiency of ~98%, and by recirculating, the output concentration of the sample was 500 times higher than the initial input. Finally, the investigation of results showed that the magnitude of CFN relies entirely on the microchannel geometry, and it is independent of the overall width of the channel cross-section. We envision that this concept of particle focusing through complex cross-sections will prove useful in paving the way towards more efficient inertial microfluidic devices.
Raoufi, MA, Bazaz, SR, Niazmand, H, Rouhi, O, Asadnia, M, Razmjou, A & Warkiani, ME 2020, 'Fabrication of unconventional inertial microfluidic channels using wax 3D printing', SOFT MATTER, vol. 16, no. 10, pp. 2448-2459.View/Download from: Publisher's site
Razavi Bazaz, S, Rouhi, O, Raoufi, MA, Ejeian, F, Asadnia, M, Jin, D & Ebrahimi Warkiani, M 2020, '3D Printing of Inertial Microfluidic Devices', Scientific Reports, vol. 10, no. 1.View/Download from: Publisher's site
© 2020, The Author(s). Inertial microfluidics has been broadly investigated, resulting in the development of various applications, mainly for particle or cell separation. Lateral migrations of these particles within a microchannel strictly depend on the channel design and its cross-section. Nonetheless, the fabrication of these microchannels is a continuous challenging issue for the microfluidic community, where the most studied channel cross-sections are limited to only rectangular and more recently trapezoidal microchannels. As a result, a huge amount of potential remains intact for other geometries with cross-sections difficult to fabricate with standard microfabrication techniques. In this study, by leveraging on benefits of additive manufacturing, we have proposed a new method for the fabrication of inertial microfluidic devices. In our proposed workflow, parts are first printed via a high-resolution DLP/SLA 3D printer and then bonded to a transparent PMMA sheet using a double-coated pressure-sensitive adhesive tape. Using this method, we have fabricated and tested a plethora of existing inertial microfluidic devices, whether in a single or multiplexed manner, such as straight, spiral, serpentine, curvilinear, and contraction-expansion arrays. Our characterizations using both particles and cells revealed that the produced chips could withstand a pressure up to 150 psi with minimum interference of the tape to the total functionality of the device and viability of cells. As a showcase of the versatility of our method, we have proposed a new spiral microchannel with right-angled triangular cross-section which is technically impossible to fabricate using the standard lithography. We are of the opinion that the method proposed in this study will open the door for more complex geometries with the bespoke passive internal flow. Furthermore, the proposed fabrication workflow can be adopted at the production level, enabling large-scale manufacturing of inertial micro...
Rzhevskiy, AS, Razavi Bazaz, S, Ding, L, Kapitannikova, A, Sayyadi, N, Campbell, D, Walsh, B, Gillatt, D, Ebrahimi Warkiani, M & Zvyagin, AV 2020, 'Rapid and Label-Free Isolation of Tumour Cells from the Urine of Patients with Localised Prostate Cancer Using Inertial Microfluidics.', Cancers, vol. 12, no. 1.View/Download from: Publisher's site
During the last decade, isolation of circulating tumour cells via blood liquid biopsy of prostate cancer (PCa) has attracted significant attention as an alternative, or substitute, to conventional diagnostic tests. However, it was previously determined that localised forms of PCa shed a small number of cancer cells into the bloodstream, and a large volume of blood is required just for a single test, which is impractical. To address this issue, urine has been used as an alternative to blood for liquid biopsy as a truly non-invasive, patient-friendly test. To this end, we developed a spiral microfluidic chip capable of isolating PCa cells from the urine of PCa patients. Potential clinical utility of the chip was demonstrated using anti-Glypican-1 (GPC-1) antibody as a model of the primary antibody in immunofluorescent assay for identification and detection of the collected tumour cells. The microchannel device was first evaluated using DU-145 cells in a diluted Dulbecco's phosphate-buffered saline sample, where it demonstrated >85 (±6) % efficiency. The microchannel proved to be functional in at least 79% of cases for capturing GPC1+ putative tumour cells from the urine of patients with localised PCa. More importantly, a correlation was found between the amount of the captured GPC1+ cells and crucial diagnostic and prognostic parameter of localised PCa-Gleason score. Thus, the technique demonstrated promise for further assessment of its diagnostic value in PCa detection, diagnosis, and prognosis.
Shrestha, J, Bazaz, SR, Es, HA, Azari, DY, Thierry, B, Warkiani, ME & Ghadiri, M 2020, 'Lung-on-a-chip: the future of respiratory disease models and pharmacological studies', CRITICAL REVIEWS IN BIOTECHNOLOGY, vol. 40, no. 2, pp. 213-230.View/Download from: Publisher's site
Vasilescu, SA, Bazaz, SR, Jin, D, Shimoni, O & Warkiani, ME 2020, '3D printing enables the rapid prototyping of modular microfluidic devices for particle conjugation', Applied Materials Today, vol. 20.View/Download from: Publisher's site
© 2020 Elsevier Ltd Antibody micro/nano-particle conjugates have proven to be essential tools in many diagnostic and nanomedicine applications. However, their production with homogenous coating and in a continuous fashion remains a tedious, labor-intensive, and costly process. In this regard, 3D micromixer-based microfluidic devices offer significant advantages over existing methods, where manipulating the flow in three dimensions increases fluid contact area and surface disruption, facilitating efficient mixing. While conventional softlithography is capable of fabricating simple 2D micromixers, complications arise when processing 3D structures. In this paper, we report the direct fabrication of a 3D complex microchannel design using additive manufacturing for the continuous conjugation of antibodies onto particle surfaces. This method benefits from a reduction in cost and time (from days to hours), simplified fabrication process, and limited post-processing. The flexibility of direct 3D printing allows quick and easy tailoring of design features to facilitate the production of micro and nanoparticles conjugated with functional antibodies in a continuous mixing process. We demonstrate that the produced antibody-functionalized particles retain their functionality by a firm and specific interaction with antigen presenting cells. By connecting 3D printed micromixers across the conjugation process, we illustrate the role of 3D printed microchannels as modularized components. The 3D printing method we report enables a broad spectrum of researchers to produce complex microfluidic geometries within a short time frame.
Zhand, S, Razmjou, A, Azadi, S, Bazaz, SR, Shrestha, J, Jahromi, MAF & Warkiani, ME 2020, 'Metal-Organic Framework-Enhanced ELISA Platform for Ultrasensitive Detection of PD-L1', ACS Applied Bio Materials, vol. 3, no. 7, pp. 4148-4158.View/Download from: Publisher's site
© 2020 American Chemical Society. The programmed cell death ligand 1 (PD-L1) protein has emerged as a predictive cancer biomarker and sensitivity to immune checkpoint blockade-based cancer immunotherapies. Current technologies for the detection of protein-based biomarkers, including the enzyme-linked immunosorbent assay (ELISA), have limitations such as low sensitivity and limit of detection (LOD) in addition to degradation of antibodies in exposure to environmental changes such as temperature and pH. To address these issues, we have proposed a metal-organic framework (MOF)-based ELISA for the detection of the PD-L1. A protective coating based on Zeolitic Imidazolate Framework 8 (ZIF-8) MOF thin film and polydopamine-polyethylenimine (PDA-PEI) was introduced on an ELISA plate for the improvement of antibody immobilization. Sensitivity and LOD of the resulting platform were compared with a conventional ELISA kit, and the bioactivity of the antibody in the proposed immunoassay was investigated in response to various pH and temperature values. The LOD and sensitivity of the MOF-based PD-L1 ELISA were 225 and 15.12 times higher, respectively, compared with those of the commercial ELISA kit. The antibody@ZIF-8/PDA-PEI was stable up to 55 °C and the pH range 5-10. The proposed platform can provide sensitive detection for target proteins, in addition to being resistant to elevated temperature and pH. The proposed MOF-based ELISA has significant potential for the clinical and diagnostic studies.
Abbasi, QH, Kiourti, A, Heidari, H, He, Y, Ebrahimi Warkiani, M & Alomainy, A 2019, 'IEEE Access Special Section Editorial: Wearable and Implantable Devices and Systems', IEEE Access, vol. 7, pp. 139512-139517.View/Download from: Publisher's site
© 2013 IEEE. Circuit techniques, sensors, antennas and communications systems are envisioned to help build new technologies over the next several years. Advances in the development and implementation of such technologies have already shown us their unique potential in realizing next-generation sensing systems. Applications include wearable consumer electronics, healthcare monitoring systems, and soft robotics, as well as wireless implants. There have been some interesting developments in the areas of circuits and systems, involving studies related to low-power electronics, wireless sensor networks, wearable circuit behaviour, security, real-time monitoring, connectivity of sensors, and Internet of Things (IoT). The direction for the current technology is electronics systems on large area electronics, integrated implantable systems and wearable sensors. So far, the research in the field has focused on materials, new processing techniques and one-off devices, such as diodes and transistors. However, current technology is not sufficient for future electronics to be useful in new applications; a great demand exists to scale up the research towards circuits and systems. Recent developments indicate that, in addition to fabrication technology, special attention should also be given to design, simulation and modeling of electronics, while keeping sensing system integration, power management, and sensors network under consideration.
Ashtari, K, Nazari, H, Ko, H, Tebon, P, Akhshik, M, Akbari, M, Alhosseini, SN, Mozafari, M, Mehravi, B, Soleimani, M, Ardehali, R, Ebrahimi Warkiani, M, Ahadian, S & Khademhosseini, A 2019, 'Electrically conductive nanomaterials for cardiac tissue engineering.', Advanced drug delivery reviews, vol. 144, pp. 162-179.View/Download from: Publisher's site
Patient deaths resulting from cardiovascular diseases are increasing across the globe, posing the greatest risk to patients in developed countries. Myocardial infarction, as a result of inadequate blood flow to the myocardium, results in irreversible loss of cardiomyocytes which can lead to heart failure. A sequela of myocardial infarction is scar formation that can alter the normal myocardial architecture and result in arrhythmias. Over the past decade, a myriad of tissue engineering approaches has been developed to fabricate engineered scaffolds for repairing cardiac tissue. This paper highlights the recent application of electrically conductive nanomaterials (carbon and gold-based nanomaterials, and electroactive polymers) to the development of scaffolds for cardiac tissue engineering. Moreover, this work summarizes the effects of these nanomaterials on cardiac cell behavior such as proliferation and migration, as well as cardiomyogenic differentiation in stem cells.
Azadi, S, Tafazzoli-Shadpour, M, Soleimani, M & Ebrahimi Warkiani, M 2019, 'Modulating cancer cell mechanics and actin cytoskeleton structure by chemical and mechanical stimulations.', Journal of biomedical materials research. Part A, vol. 107, no. 8, pp. 1569-1581.View/Download from: Publisher's site
To date, a myriad of strategies has been suggested for targeting the chemical signaling of cancer cells. Also, biomechanical features are gaining much more attention. These features can be used as biomarkers which influence cancer progression. Current approaches on cancer treatment are mainly focused on changing the biochemical signaling of cancer cells, whereas less attention was devoted to their biomechanical properties. Herein, we propose targeting of cancer cell mechanics through the microenvironmental mechanical and chemical cues. As such, we examined the role of substrate stiffness as well as the effect of epidermal growth factor receptor (EGFR) blockade in the cell mechanics. As a mechanical stimulus, stiff and soft polydimethylsiloxane substrates were utilized, while as a chemical stimulus, EGFR blockade was considered. Thus, breast cancer cell lines, MCF7 and MDA-MB-231, were cultured among chemical and mechanical groups. The local elasticity of cancer cells was assessed by atomic force microscopy nanoindentation method. Furthermore, we evaluated the effect of mentioned mechanical and chemical treatments on the morphology, actin cytoskeleton structures, and cancer cell migration abilities. The stiffness and migration ability of cancer cells increased by substrate stiffening while Cetuximab treatment demonstrated an elevation in the elastic modulus of cells followed by a reduction in the migration ability. These findings indicate that cancer cell mechanics is modulated not only by the mechanical cues but also by the chemical ones through EGFR signaling pathway. Overall, our results illustrate that manipulation of cell mechanics allows for the possible modulation of tumor cell migration. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1569-1581, 2019.
Condina, MR, Dilmetz, BA, Bazaz, SR, Meneses, J, Warkiani, ME & Hoffmann, P 2019, 'Rapid separation and identification of beer spoilage bacteria by inertial microfluidics and MALDI-TOF mass spectrometry', LAB ON A CHIP, vol. 19, no. 11, pp. 1961-1970.View/Download from: Publisher's site
Derakhshani, M, Abbaszadeh, H, Movassaghpour, AA, Mehdizadeh, A, Ebrahimi Warkiani, M & Yousefi, M 2019, 'Strategies for elevating hematopoietic stem cells expansion and engraftment capacity.', Life sciences, vol. 232.View/Download from: Publisher's site
Hematopoietic stem cells (HSCs) are a rare cell population in adult bone marrow, mobilized peripheral blood, and umbilical cord blood possessing self-renewal and differentiation capability into a full spectrum of blood cells. Bone marrow HSC transplantation has been considered as an ideal option for certain disorders treatment including hematologic diseases, leukemia, immunodeficiency, bone marrow failure syndrome, genetic defects such as thalassemia, sickle cell anemia, autoimmune disease, and certain solid cancers. Ex vivo proliferation of these cells prior to transplantation has been proposed as a potential solution against limited number of stem cells. In such culture process, MSCs have also been shown to exhibit high capacity for secretion of soluble mediators contributing to the principle biological and therapeutic activities of HSCs. In addition, endothelial cells have been introduced to bridge the blood and sub tissues in the bone marrow, as well as, HSCs regeneration induction and survival. Cell culture in the laboratory environment requires cell growth strict control to protect against contamination, symmetrical cell division and optimal conditions for maximum yield. In this regard, microfluidic systems provide culture and analysis capabilities in micro volume scales. Moreover, two-dimensional cultures cannot fully demonstrate extracellular matrix found in different tissues and organs as an abstract representation of three dimensional cell structure. Microfluidic systems can also strongly describe the effects of physical factors such as temperature and pressure on cell behavior.
Ejeian, F, Azadi, S, Razmjou, A, Orooji, Y, Kottapalli, A, Ebrahimi Warkiani, M & Asadnia, M 2019, 'Design and applications of MEMS flow sensors: A review', Sensors and Actuators, A: Physical, vol. 295, pp. 483-502.View/Download from: Publisher's site
© 2019 Elsevier B.V. There is an indispensable need for fluid flow rate and direction sensors in various medical, industrial and environmental applications. Besides the critical demands on sensing range of flow parameters (such as rate, velocity, direction and temperature), the properties of different target gases or liquids to be sensed pose challenges to the development of reliable, inexpensive and low powered sensors. This paper presents an overview of the work done on design and development of Microelectromechanical system (MEMS)-based flow sensors in recent years. In spite of using some similar principles, diverse production methods, analysis strategies, and different sensing materials, MEMS flow sensors can be broadly categorized into three main types, namely thermal sensors, piezoresistive sensors and piezoelectric sensors. Additionally, some key challenges and future prospects for the use of the MEMS flow sensors are discussed briefly.
Gerami, A, Alzahid, Y, Mostaghimi, P, Kashaninejad, N, Kazemifar, F, Amirian, T, Mosavat, N, Ebrahimi Warkiani, M & Armstrong, RT 2019, 'Microfluidics for Porous Systems: Fabrication, Microscopy and Applications', Transport in Porous Media, vol. 130, pp. 277-304.View/Download from: Publisher's site
© 2018, Springer Nature B.V. No matter how sophisticated the structures are and on what length scale the pore sizes are, fluid displacement in porous media can be visualized, captured, mimicked and optimized using microfluidics. Visualizing transport processes is fundamental to our understanding of complex hydrogeological systems, petroleum production, medical science applications and other engineering applications. Microfluidics is an ideal tool for visual observation of flow at high temporal and spatial resolution. Experiments are typically fast, as sample volume is substantially low with the use of miniaturized devices. This review first discusses the fabrication techniques for generating microfluidics devices, experimental setups and new advances in microfluidic fabrication using three-dimensional printing, geomaterials and biomaterials. We then address multiphase transport in subsurface porous media, with an emphasis on hydrology and petroleum engineering applications in the past few decades. We also cover the application of microfluidics to study membrane systems in biomedical science and particle sorting. Lastly, we explore how synergies across different disciplines can lead to innovations in this field. A number of problems that have been resolved, topics that are under investigation and cutting-edge applications that are emerging are highlighted.
Ghorbani, F, Abbaszadeh, H, Mehdizadeh, A, Ebrahimi Warkiani, M, Rashidi, M-R & Yousefi, M 2019, 'Biosensors and nanobiosensors for rapid detection of autoimmune diseases: a review.', Mikrochimica acta, vol. 186, no. 12.View/Download from: Publisher's site
This review (with 77 refs.) describes the progress that has been made in biosensors for the detection of autoimmune diseases, mainly via detection of autoantibodies. In addition, specific proteins, cytokines and ions have also been introduced as promising diagnostic biomarkers. Following an introduction into the various kinds of autoimmune diseases, we first discuss the state of the art in respective electrochemical biosensors and nanobiosensors (with subsections on amperometric, impedimetric, voltammetric and photoelectrochemical methods). The next large chapter covers optical methods (with subsections on electrochemiluminescence, fluorescence and surface plasmon resonance). We then make a critical comparison between commercially available kits used for detection of autoimmune diseases with the established biosensors. Several Tables are also presented that give an overview on the wealth of methods and nanomaterials. Finally, in the conclusion part, we summarize the current status, addresse present issues, and give an outlook on potential future opportunities. Graphical abstractSchematic representation of various developed optical and electrochemical biosensors and nanobiosensors for rapid detection of autoimmune diseases nanobiosensors for rapid detection of autoimmune diseases which could significantly prevent irreversable tissue damages and increse the quality of life in these patients.
Ghorbani, S, Eyni, H, Khosrowpour, Z, Salari Asl, L, Shabani, R, Nazari, H, Mehdizadeh, M, Ebrahimi Warkiani, M & Amjadi, FS 2019, 'Spermatogenesis induction of spermatogonial stem cells using nanofibrous poly(l-lactic acid)/multi-walled carbon nanotube scaffolds and naringenin', Polymers for Advanced Technologies, vol. 30, no. 12, pp. 3011-3025.View/Download from: Publisher's site
© 2019 John Wiley & Sons, Ltd. Spermatogenesis is a process in which animals generate spermatozoa from spermatogonial stem cells (SSCs). Successful in vitro differentiation of SSCs towards spermatids holds a significant promise for regeneration of impaired spermatogenesis. The present study aims to evaluate the efficiency of a 3D culture containing naringenin on proliferation and differentiation potentials of mouse SSCs. In this study, multi-walled carbon nanotubes (MWCNTs) were incorporated into poly(l-lactic acid) (PLLA) fibers via electrospinning technique. The fibrous PLLA/MWCNTs were studied by Fourier-transform infrared spectroscopy (FTIR), transmission electron microscope (TEM), water contact angle measurements, electrical conductivity, and mechanical properties. Next, the SSCs were seeded into the PLLA/MWCNTs scaffolds and exhibited preferable survival and differentiation efficiency to subsequent cell lines. To shed more light on this matter, the immunocytochemistry, reverse-transcription polymerase chain reaction (RT-PCR), and qRT-PCR results showed that the aforementioned cells on the 3D fabrics overexpressed the C-kit and SYCP3 proteins. In addition, the reactive oxygen species (ROS) measurement data demonstrated that naringenin, an effective antioxidant, plays an important role in in vitro spermatogenesis. Taken together, the results of this study revealed the synergistic effects of 3D scaffolds and naringenin for efficient spermatogenesis in laboratories.
Guo, Z, Yang, CT, Maritz, MF, Wu, H, Wilson, P, Chien, CC, Kempson, I, Aref, AR, Thierry, B & Ebrahimi Warkiani, M 2019, 'Validation of a Vasculogenesis Microfluidic Model for Radiobiological Studies of the Human Microvasculature', Advanced Materials Technologies, vol. 4, no. 4.View/Download from: Publisher's site
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim The therapeutic ratio of radiotherapy is limited by acute or chronic side effects with often severe consequences to patients. The microvasculature is a central player involved in both tumor responses and healthy tissue/organ radiological injuries. However, current preclinical vascular models based on 2D culture offer only limited radiobiological insight due to their failure in recapitulating the 3D nature experienced by endothelial cells within the human microvasculature. To address this issue, the use of a 3D microvasculature-on-a-chip microfluidic technology is demonstrated in radiobiological studies. Within this vasculogenesis model a perfusable network that structurally mimics the human microvasculature is formed and the biological response to ionizing radiation including cellular apoptosis, vessel tight adherens junction breakage, DNA double strand break, and repair is systematically investigated. In comparison to cells grown in a 2D environment, human umbilical vein endothelial cells in the 3D microvasculature-on-a-chip displays significant differences in biological responses, especially at high X-ray dose. This data confirms the feasibility of using microvascular-on-a-chip models for radiobiological studies. Such vasculogenesis models have strong potential to yield more accurate prediction of healthy tissue responses to ionizing radiation as well as to guide the development of risk-reducing strategies to prevent radiation-induced acute and long-term side-effects.
Kulasinghe, A, Kapeleris, J, Cooper, C, Ebrahimi Warkiani, M, O'Byrne, K & Punyadeera, C 2019, 'Phenotypic Characterization of Circulating Lung Cancer Cells for Clinically Actionable Targets.', Cancers, vol. 11, no. 3.View/Download from: Publisher's site
OBJECTIVES:In non-small cell lung cancers (NSCLC), tumour biopsy can often be an invasive procedure. The development of a non-invasive methodology to study genetic changes via circulating tumour cells (CTCs) is an appealing concept. Whilst CTCs typically remain as rare cells, improvements in epitope-independent CTC isolation techniques has given rise to a greater capture of CTCs. In this cross sectional study, we demonstrate the capture and characterization of NSCLC CTCs for the clinically actionable markers epidermal growth factor receptor (EGFR) alterations, anaplastic lymphoma kinase (ALK) rearrangements and programmed death ligand-1 (PD-L1) expression. The study identified CTCs/CTC clusters in 26/35 Stage IV NSCLC patients, and subsequently characterized the CTCs for EGFR mutation, ALK status and PD-L1 status. This pilot study demonstrates the potential of a non-invasive fluid biopsy to determine clinically relevant biomarkers in NSCLC.
Mahmoodi, Z, Mohammadnejad, J, Bazaz, SR, Mehrizi, AA, Ghiass, MA, Saidijam, M, Dinarvand, R, Warkiani, ME & Soleimani, M 2019, 'A simple coating method of PDMS microchip with PTFE for synthesis of dexamethasone-encapsulated PLGA nanoparticles', DRUG DELIVERY AND TRANSLATIONAL RESEARCH, vol. 9, no. 3, pp. 707-720.View/Download from: Publisher's site
Moloudi, R, Oh, S, Yang, C, Teo, KL, Lam, AT-L, Ebrahimi Warkiani, M & Win Naing, M 2019, 'Scaled-Up Inertial Microfluidics: Retention System for Microcarrier-Based Suspension Cultures.', Biotechnology Journal, vol. 14, no. 5.View/Download from: Publisher's site
Recently, particle concentration and filtration using inertial microfluidics have drawn attention as an alternative to membrane and centrifugal technologies for industrial applications, where the target particle size varies between 1 µm and 500 µm. Inevitably, the bigger particle size (>50 µm) mandates scaling up the channel cross-section or hydraulic diameter (DH > 0.5 mm). The Dean-coupled inertial focusing dynamics in spiral microchannels is studied broadly; however, the impacts of secondary flow on particle migration in a scaled-up spiral channel is not fully elucidated. The mechanism of particle focusing inside scaled-up rectangular and trapezoidal spiral channels (i.e., 5-10× bigger than conventional microchannels) with an aim to develop a continuous and clog-free microfiltration system for bioprocessing is studied in detail. Herein, a unique focusing based on inflection point without the aid of sheath flow is reported. This new focusing mechanism, observed in the scaled-up channels, out-performs the conventional focusing scenarios in the previously reported trapezoidal and rectangular channels. Finally, as a proof-of-concept, the utility of this device is showcased for the first time as a retention system for a cell-microcarrier (MC) suspension culture.
Rafeie, M, Hosseinzadeh, S, Huang, J, Mihandoust, A, Ebrahimi Warkiani, M & Taylor, RA 2019, 'New insights into the physics of inertial microfluidics in curved microchannels. II. Adding an additive rule to understand complex cross-sections.', Biomicrofluidics, vol. 13, no. 3.View/Download from: Publisher's site
Curved microchannels allow controllable microparticle focusing, but a full understanding of particle behavior has been limited-even for simple rectangular and trapezoidal shapes. At present, most microfluidic particle separation literature is dedicated to adding "internal" complexity (via sheath flow or obstructions) to relatively simple cross-sectional channel shapes. We propose that, with sufficient understanding of particle behavior, an equally viable pathway for microparticle focusing could utilize complex "external" cross-sectional shapes. By investigating three novel, complex spiral microchannels, we have found that it is possible to passively focus (6, 10, and 13 μm) microparticles in the middle of a convex channel. Also, we found that in concave and jagged channel designs, it is possible to create multiple, tight focusing bands. In addition to these performance benefits, we report an "additive rule" herein, which states that complex channels can be considered as multiple, independent, simple cross-sectional shapes. We show with experimental and numerical analysis that this new additive rule can accurately predict particle behavior in complex cross-sectional shaped channels and that it can help to extract general inertial focusing tendencies for suspended particles in curved channels. Overall, this work provides simple, yet reliable, guidelines for the design of advanced curved microchannel cross sections.
Rafeie, M, Hosseinzadeh, S, Taylor, RA & Ebrahimi Warkiani, M 2019, 'New insights into the physics of inertial microfluidics in curved microchannels. I. Relaxing the fixed inflection point assumption.', Biomicrofluidics, vol. 13, no. 3.View/Download from: Publisher's site
Inertial microfluidics represents a powerful new tool for accurately positioning cells and microparticles within fluids for a variety of biomedical, clinical, and industrial applications. In spite of enormous advancements in the science and design of these devices, particularly in curved microfluidic channels, contradictory experimental results have confounded researchers and limited progress. Thus, at present, a complete theory which describes the underlying physics is lacking. We propose that this bottleneck is due to one simple mistaken assumption-the locations of inflection points of the Dean velocity profile in curved microchannels are not fixed, but can actually shift with the flow rate. Herein, we propose that the dynamic distance (δ) between the real equilibrium positions and their nearest inflection points can clearly explain several (previously) unexplained phenomena in inertial microfluidic systems. More interestingly, we found that this parameter, δ, is a function of several geometric and operational parameters, all of which are investigated (in detail) here with a series of experiments and simulations of different spiral microchannels. This key piece of understanding is expected to open the door for researchers to develop new and more effective inertial microfluidic designs.
Raoufi, MA, Mashhadian, A, Niazmand, H, Asadnia, M, Razmjou, A & Ebrahimi Warkiani, M 2019, 'Experimental and numerical study of elasto-inertial focusing in straight channels.', Biomicrofluidics, vol. 13, no. 3, pp. 034103-034103.View/Download from: Publisher's site
Elasto-inertial microfluidics has drawn significant attention in recent years due to its enhanced capabilities compared to pure inertial systems in control of small microparticles. Previous investigations have focused mainly on the applications of elasto-inertial sorting, rather than studying its fundamentals. This is because of the complexity of simulation and analysis, due to the presence of viscoelastic force. There have been some investigative efforts on the mechanisms of elasto-inertial focusing in straight channels; however, these studies were limited to simple rectangular channels and neglected the effects of geometry and flow rates on focusing positions. Herein, for the first time, we experimentally and numerically explore the effects of elasticity accompanying channel cross-sectional geometry and sample flow rates on the focusing phenomenon in elasto-inertial systems. The results reveal that increasing the aspect ratio weakens the elastic force more than inertial force, causing a transition from one focusing position to two. In addition, they show that increasing the angle of a channel corner causes the elastic force to push the particles more efficiently toward the center over a larger area of the channel cross section. Following on from this, we proposed a new complex straight channel which demonstrates a tighter focusing band compared to other channel geometries. Finally, we focused Saccharomyces cerevisiae cells (3-5 μm) in the complex channel to showcase its capability in focusing small-size particles. We believe that this research work improves the understanding of focusing mechanisms in viscoelastic solutions and provides useful insights into the design of elasto-inertial microfluidic devices.
Raoufi, MA, Moshizi, SA, Razmjou, A, Wu, S, Ebrahimi Warkiani, M & Asadnia, M 2019, 'Development of a Biomimetic Semicircular Canal With MEMS Sensors to Restore Balance', IEEE Sensors Journal, vol. 19, no. 23, pp. 11675-11686.View/Download from: Publisher's site
Azadi, S, ABOULKHEYR ESTARABADI, H, Razavi Bazaz, S, Thiery, JP, Asadnia, M & Ebrahimi Warkiani, M 2019, 'Upregulation of PD-L1 expression in breast cancer cells through the formation of 3D multicellular cancer aggregates under different chemical and mechanical conditions.', Biochimica et biophysica acta. Molecular cell research, vol. 1866, no. 12.View/Download from: Publisher's site
Expression of programmed death-ligand 1 (PD-L1) in cancer cells plays an important role in cancer-immune cell interaction. The emerging evidence suggests regulation of PD-L1 expression by several tumor microenvironmental cues. However, the association of PD-L1 expression with chemical and mechanical features of the tumor microenvironment, specifically epidermal growth factor receptor (EGFR) signaling and matrix stiffness, remains elusive. Herein, we determine whether EGFR targeting and substrate stiffness affect the regulation of PD-L1 expression. Breast carcinoma cell lines, MCF7 and MDA-MB-231, were cultured under different conditions targeting EGFR and exposing cells to distinct substrate stiffness to evaluate PD-L1 expression. Furthermore, the ability to form aggregates in short-term culture of breast carcinoma cells and its effect on expression level of PD-L1 was probed. Our results indicated that PD-L1 expression was altered in response to both EGFR inhibition and substrate stiffness. Additionally, a positive association between the formation of multicellular aggregates and PD-L1 expression was observed. MDA-MB-231 cells expressed the highest PD-L1 level on a stiff substrate, while inhibition of EGFR reduced expression of PD-L1. The results suggested that both physical and chemical features of tumor microenvironment regulate PD-L1 expression through alteration of tumor aggregate formation potential. In line with these results, the in-silico study highlighted a positive correlation between PD-L1 expression, EGFR signaling, epithelial to mesenchymal transition related transcription factors (EMT-TFs) and stemness markers in metastatic breast cancer. These findings improve our understanding of regulation of PD-L1 expression by tumor microenvironment leading to evasion of tumor cells from the immune system.
Biglari, S, Le, TYL, Tan, RP, Wise, SG, Zambon, A, Codolo, G, De Bernard, M, Ebrahimi Warkiani, M, Schindeler, A, Naficy, S, Valtchev, P, Khademhosseini, A & Dehghani, F 2019, 'Simulating Inflammation in a Wound Microenvironment Using a Dermal Wound-on-a-Chip Model.', Advanced Healthcare Materials, vol. 8, no. 1.View/Download from: Publisher's site
Considerable progress has been made in the field of microfluidics to develop complex systems for modeling human skin and dermal wound healing processes. While microfluidic models have attempted to integrate multiple cell types and/or 3D culture systems, to date they have lacked some elements needed to fully represent dermal wound healing. This paper describes a cost-effective, multicellular microfluidic system that mimics the paracrine component of early inflammation close to normal wound healing. Collagen and Matrigel are tested as materials for coating and adhesion of dermal fibroblasts and human umbilical vein endothelial cells (HUVECs). The wound-on-chip model consists of three interconnecting channels and is able to simulate wound inflammation by adding tumor necrosis factor alpha (TNF-α) or by triculturing with macrophages. Both the approaches significantly increase IL-1β, IL-6, IL-8 in the supernatant (p < 0.05), and increases in cytokine levels are attenuated by cotreatment with an anti-inflammatory agent, Dexamethasone. Incorporation of M1 and M2 macrophages cocultured with fibroblasts and HUVECs leads to a stimulation of cytokine production as well as vascular structure formation, particularly with M2 macrophages. In summary, this wound-on-chip system can be used to model the paracrine component of the early inflammatory phase of wound healing and has the potential for the screening of anti-inflammatory compounds.
Razavi Bazaz, S, Kashaninejad, N, Azadi, S, Patel, K, Asadnia, M, Jin, D & Ebrahimi Warkiani, M 2019, 'Rapid Softlithography Using 3D-Printed Molds', Advanced Materials Technologies, vol. 4.View/Download from: Publisher's site
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Polydimethylsiloxane (PDMS) is a long-standing material of significant interest in microfluidics due to its unique features. As such, rapid prototyping of PDMS-based microchannels is of great interest. The most prevalent and conventional method for fabrication of PDMS-based microchips relies on softlithography, the main drawback of which is the preparation of a master mold, which is costly and time-consuming. To prevent the attachment of PDMS to the master mold, silanization is necessary, which can be detrimental for cellular studies. Additionally, using coating the mold with a cell-compatible surfactant adds extra preprocessing time. Recent advances in 3D printing have shown great promise in expediting microfabrication. Nevertheless, current 3D printing techniques are sub-optimal for PDMS softlithography. The feasibility of producing master molds suitable for rapid softlithography is demonstrated using a newly developed 3D-printing resin. Moreover, the utility of this technique is showcased for a number of widely used applications, such as concentration gradient generation, particle separation, cell culture (to show biocompatibility of the process), and fluid mixing. This can open new opportunities for biologists and scientists with minimum knowledge of microfabrication to build functional microfluidic devices for their basic and applied research.
Rezaei, M, Winter, M, Zander-Fox, D, Whitehead, C, Liebelt, J, Ebrahimi Warkiani, M, Hardy, T & Thierry, B 2019, 'A Reappraisal of Circulating Fetal Cell Noninvasive Prenatal Testing.', Trends in biotechnology, vol. 37, no. 6, pp. 632-644.View/Download from: Publisher's site
New tools for higher-resolution fetal genome analysis including microarray and next-generation sequencing have revolutionized prenatal screening. This article provides commentary on this rapidly advancing field and a future perspective emphasizing circulating fetal cell (CFC) utility. Despite the tremendous technological challenges associated with their reliable and cost-effective isolation from maternal blood, CFCs have a strong potential to bridge the gap between the diagnostic sensitivity of invasive procedures and the desirable noninvasive nature of cell-free fetal DNA (cffDNA). Considering the rapid advances in both rare cell isolation and low-input DNA analysis, we argue here that CFC-based noninvasive prenatal testing is poised to be implemented clinically in the near future.
Winter, M, Cai, Z, Winkler, K, Georgiou, K, Inglis, D, Lavranos, T, Rezaei, M, Ebrahimi Warkiani, M & Thierry, B 2019, 'Circulating tumour cell RNA characterisation from colorectal cancer patient blood after inertial microfluidic enrichment', MethodsX, vol. 6, pp. 1512-1520.View/Download from: Publisher's site
© 2019 The Authors The detection and molecular analysis of circulating tumour cells (CTCs) potentially provides a significant insight to the characterisation of disease, stage of progression and therapeutic options for cancer patients. Following on from the protocol by Warkiani et al. 2016, which describes a method of enriching CTCs from cancer patient blood with inertial microfluidics, we describe a method to measure the CTC RNA expression in the enriched fraction using droplet digital PCR and compare transcript detection with and without RNA pre-amplification. • Inertial microfluidics combined with droplet digital PCR is advantageous as it allows for CTC enrichment and subsequent RNA analysis from patient blood. This allows for patient tumour analysis with increased sensitivity and precision compared to quantitative Real Time PCR and enables the direct quantification of nucleic acids without the need for tumour biopsy. • This method demonstrates an efficient approach providing important insights into the analysis of colorectal cancer patients' CTCs using a specific gene subset or biomarkers, an approach that may be tailored to tumour type or expanded to larger panels.
Abbasnejad, B, Thorby, W, Razmjou, A, Jin, D, Asadnia, M & Ebrahimi Warkiani, M 2018, 'MEMS piezoresistive flow sensors for sleep apnea therapy', Sensors and Actuators, A: Physical, vol. 279, pp. 577-585.View/Download from: Publisher's site
© 2018 Elsevier B.V. A MEMS liquid crystal polymer (LCP), used in the membrane-based pressure sensor, has been found highly useful as a flow sensor. Here we conducted a set of elaborate experiments using an air flow generator to investigate the potential of our LCP flow sensor for sleep apnea therapy. Critical properties of the LCP flow sensor, including flow range, resolution (sensitivity), accuracy, and response time, have been systematically characterized. As a result, LCP flow sensor achieves a limit of detection of 8 LPM to measure flow rate, better than the commercial flow sensor (>10 LPM). Our LCP flow sensor shows a favourable response in a large flow range (8–160 LPM) with a sensitivity of detecting a linear voltage response of 0.004 V per 1 LPM flow rate. With minimum detectable flow, high sensitivity and resolution, we further demonstrated our LCP flow sensor for detecting human respiration. Moreover, using a two- dimensional simulation in COMSOL Multiphysics, we demonstrated the deformation of LCP membrane in response to different flow velocities which leads to resistance change in sensor's strain gauge.
Ghorbani, S, Eyni, H, Tiraihi, T, Asl, LS, Soleimani, M, Atashi, A, Beiranvand, SP & Warkiani, ME 2018, 'Combined effects of 3D bone marrow stem cell-seeded wet-electrospun poly lactic acid scaffolds on full-thickness skin wound healing', International Journal of Polymeric Materials and Polymeric Biomaterials, vol. 67, no. 15, pp. 905-912.View/Download from: Publisher's site
© 2017 Taylor & Francis. Tissue engineering has emerged as an alternative treatment to traditional grafts for skin wound healing. Three-dimensional nanofibers have been used extensively for this purpose due to their excellent biomedical-related properties. In this study, high porous 3D poly lactic acid nanofibrous scaffolds (PLA-S) were prepared by wet-electrospinning technique and seeded with rat bone-marrow stem cells (BMSCs) to characterize the biocompatibility and therapeutic efficacy of these fibers on the treating full-thickness dermal wounds. The results of in vitro andin vivo studies indicate that the 3D fibrous PLA-S can be a potential wound dressing for wound repair, particularly when seeded with BMSCs. GRAPHICAL ABSTRACT.
Hassanzadeh-Barforoushi, A, Law, AMK, Hejri, A, Asadnia, M, Ormandy, CJ, Gallego-Ortega, D & Ebrahimi Warkiani, M 2018, 'Static droplet array for culturing single live adherent cells in an isolated chemical microenvironment.', Lab on a chip, vol. 18, no. 15, pp. 2156-2166.View/Download from: Publisher's site
We present here a new method to easily and reliably generate an array of hundreds of dispersed nanoliter-volume semi-droplets for single-cells culture and analysis. The liquid segmentation step occurs directly in indexed traps by a tweezer-like mechanism and is stabilized by spatial confinement. Unlike common droplet-based techniques, the semi-droplet wets its surrounding trap walls thus supporting the culturing of both adherent and non-adherent cells. To eliminate cross-droplet cell migration and chemical cross-talk each semi-droplet is separated from a nearby trap by an ∼80 pL air plug. The overall setup and injection procedure takes less than 10 minutes, is insensitive to fabrication defects and supports cell recovery for downstream analysis. The method offers a new approach to easily capture, image and culture single cells in a chemically isolated microenvironment as a preliminary step towards high-throughput single-cell assays.
Kapeleris, J, Kulasinghe, A, Warkiani, ME, Vela, I, Kenny, L, O'Byrne, K & Punyadeera, C 2018, 'The prognostic role of circulating tumor cells (CTCs) in lung cancer', Frontiers in Oncology, vol. 8, no. AUG.View/Download from: Publisher's site
© 2018 Kapeleris, Kulasinghe, Warkiani, Vela, Kenny, O'Byrne and Punyadeera. Lung cancer affects over 1. 8 million people worldwide and is the leading cause of cancer related mortality globally. Currently, diagnosis of lung cancer involves a combination of imaging and invasive biopsies to confirm histopathology. Non-invasive diagnostic techniques under investigation include "liquid biopsies" through a simple blood draw to develop predictive and prognostic biomarkers. A better understanding of circulating tumor cell (CTC) dissemination mechanisms offers promising potential for the development of techniques to assist in the diagnosis of lung cancer. Enumeration and characterization of CTCs has the potential to act as a prognostic biomarker and to identify novel drug targets for a precision medicine approach to lung cancer care. This review will focus on the current status of CTCs and their potential diagnostic and prognostic utility in this setting.
Khan, H, Razmjou, A, Warkiani, ME, Kottapalli, A & Asadnia, M 2018, 'Sensitive and Flexible Polymeric Strain Sensor for Accurate Human Motion Monitoring', SENSORS, vol. 18, no. 2.View/Download from: Publisher's site
Kulasinghe, A, Schmidt, H, Perry, C, Whitfield, B, Kenny, L, Nelson, C, Warkiani, ME & Punyadeera, C 2018, 'A Collective Route to Head and Neck Cancer Metastasis', Scientific Reports, vol. 8, no. 1.View/Download from: Publisher's site
© 2018 The Author(s). Distant metastasis (DM) from head and neck cancers (HNC) portends a poor patient prognosis. Despite its important biological role, little is known about the cells which seed these DM. Circulating tumour cells (CTCs) represent a transient cancer cell population, which circulate in HNC patients' peripheral blood and seed at distant sites. Capture and analysis of CTCs offers insights into tumour metastasis and can facilitate treatment strategies. Whilst the data on singular CTCs have shown clinical significance, the role of CTC clusters in metastasis remains limited. In this pilot study, we assessed 60 treatment naïve HNC patients for CTCs with disease ranging from early to advanced stages, for CTC clusters utilizing spiral CTC enrichment technology. Single CTCs were isolated in 18/60-30% (Ranging from Stage I-IV), CTC clusters in 15/60-25% (exclusively Stage IV) with 3/15-20% of CTC clusters also containing leukocytes. The presence of CTC clusters associated with the development of distant metastatic disease(P = 0.0313). This study demonstrates that CTC clusters are found in locally advanced patients, and this may be an important prognostic marker. In vivo and in vitro studies are warranted to determine the role of these CTC clusters, in particular, whether leukocyte involvement in CTC clusters has clinical relevance.
Marsavela, G, Aya-Bonilla, CA, Warkiani, ME, Gray, ES & Ziman, M 2018, 'Melanoma circulating tumor cells: Benefits and challenges required for clinical application', Cancer Letters, vol. 424, pp. 1-8.View/Download from: Publisher's site
© 2018 The implementation of novel therapeutic interventions has improved the survival rates of melanoma patients with metastatic disease. Nonetheless, only 33% of treated cases exhibit long term responses. Circulating tumor cell (CTC) measurements are currently of clinical value in breast, prostate and colorectal cancers. However, the clinical utility of melanoma CTCs (MelCTCs) is still unclear due to challenges that appear intrinsic to MelCTCs (i.e. rarity, heterogeneity) and a lack of standardization in their isolation, across research laboratories. Here, we review the latest developments, pinpoint the challenges in MelCTC isolation and address their potential role in melanoma management.
Moazzam, P, Tavassoli, H, Razmjou, A, Warkiani, ME & Asadnia, M 2018, 'Mist harvesting using bioinspired polydopamine coating and microfabrication technology', Desalination, vol. 429, pp. 111-118.View/Download from: Publisher's site
© 2017 Elsevier B.V. The fascinating biopolymer of polydopamine (PDA) and negative photolithography method was utilized to produce porous membrane surfaces with contrast wettabilities via creating hydrophilic patterns (nanoscale PDA coated SU-8 bumps) on the hydrophobic background of polypropylene (PP) membranes. The high rate of water collection (97 mg cm − 2 h − 1 ) highlighted the impact of hydrophilic patterns and wetting properties on mist-harvesting results. Modified samples exhibited droplet motion by coalescence rather than rolling which means created hydrophilic patterns also have a significant impact on the behavior of the droplets on these surfaces. Surface characterization including Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM) and contact angle as well as surface free energy measurement were performed to study the effect of topography and roughness on the system performance. This created structure has the great potential to be fabricated in large scale. Also, due to the porous nature of its hydrophobic background, water collection rate can be substantially increased by using vacuum pressure, makes it attractive for industry.
Moloudi, R, Oh, S, Yang, C, Teo, KL, Lam, AT-L, Warkiani, ME & Naing, MW 2018, 'Inertial-Based Filtration Method for Removal of Microcarriers from Mesenchymal Stem Cell Suspensions', SCIENTIFIC REPORTS, vol. 8.View/Download from: Publisher's site
Moloudi, R, Oh, S, Yang, C, Warkiani, ME & Naing, MW 2018, 'Inertial particle focusing dynamics in a trapezoidal straight microchannel: application to particle filtration', MICROFLUIDICS AND NANOFLUIDICS, vol. 22, no. 3.View/Download from: Publisher's site
Moshksayan, K, Kashaninejad, N, Warkiani, ME, Lock, JG, Moghadas, H, Firoozabadi, B, Saidi, MS & Nguyen, NT 2018, 'Spheroids-on-a-chip: Recent advances and design considerations in microfluidic platforms for spheroid formation and culture', Sensors and Actuators, B: Chemical, vol. 263, pp. 151-176.View/Download from: Publisher's site
© 2018 Elsevier B.V. A cell spheroid is a three-dimensional (3D) aggregation of cells. Synthetic, in-vitro spheroids provide similar metabolism, proliferation, and species concentration gradients to those found in-vivo. For instance, cancer cell spheroids have been demonstrated to mimic in-vivo tumor microenvironments, and are thus suitable for in-vitro drug screening. The first part of this paper discusses the latest microfluidic designs for spheroid formation and culture, comparing their strategies and efficacy. The most recent microfluidic techniques for spheroid formation utilize emulsion, microwells, U-shaped microstructures, or digital microfluidics. The engineering aspects underpinning spheroid formation in these microfluidic devices are therefore considered. In the second part of this paper, design considerations for microfluidic spheroid formation chips and microfluidic spheroid culture chips (μSFCs and μSCCs) are evaluated with regard to key parameters affecting spheroid formation, including shear stress, spheroid diameter, culture medium delivery and flow rate. This review is intended to benefit the microfluidics community by contributing to improved design and engineering of microfluidic chips capable of forming and/or culturing three-dimensional cell spheroids.
© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Nature has long inspired scientists and engineers. As one ubiquitous example of this, nature has provided all with several clever methods to absorb, repel, and/or allow both sunlight and water to pass through surfaces. Moth's eyes (highly antireflective) and lotus leaves (highly hydrophobic and self-cleaning) represent durable natural surfaces which exhibit nearly ideal physical and optical properties. Man-made transparent surfaces must also be able to cope with water and dust while reaching the maximum possible light transmission for solar collectors, displays, and other optical devices. To explore the link between these – particularly for transparent surfaces – this review puts the physics, progress, and limitations of synthetic materials in context with natural materials. This perspective reveals that there is still much more to learn (and implement) if it is hoped to match the multifunctionality and resilience of natural materials.
Razavi Bazaz, S, Mehrizi, AA, Ghorbani, S, Vasilescu, S, Asadnia, M & Ebrahimi Warkiani, M 2018, 'A hybrid micromixer with planar mixing units', RSC Advances, vol. 8, no. 58, pp. 33103-33120.View/Download from: Publisher's site
© The Royal Society of Chemistry. The application of microfluidic systems in chemical and biological assays has progressed dramatically in recent years. One of the fundamental operations that microfluidic devices must achieve is a high mixing index. Of particular importance is the role of planar mixing units with repetitive obstacles (MURO) in the formation of micromixers. To date, a myriad of planar passive micromixers has been proposed. However, a strategy for the combination of these units to find an efficient planar mixer has not been investigated. As such, five different MURO have been selected to form a "hybrid micromixer," and their combination was evaluated via numerical and experimental methods. These mixing units include ellipse-like, Tesla, nozzle and pillar, teardrop, and obstruction in a curved mixing unit. Since these units have distinctive dimensions, dynamic and geometric similarities were used to scale and connect them. Afterwards, six slots were designated to house each mixing unit. Since the evaluation of all possible unit configurations is not feasible, the design of experiment method is applied to reduce the total number of experiments from 15 625 to 25. Following this procedure, the "hybrid" micromixer proposed here, comprising Tesla, nozzle and pillar, and obstruction units, shows improved performance for a wide range of Re (i.e., mixing index of >90% for Re 0.001-0.1, 22-45) over existing designs. The use of velocity profiles, concentration diagrams, vorticity and circulation plots assist in the analysis of each unit. Comparison of the proposed "hybrid" micromixer with other obstacle-based planar micromixers demonstrates improved performance, indicating the combination of planar mixing units is a useful strategy for building high-performance micromixers.
Sofela, S, Sahloul, S, Rafeie, M, Kwon, T, Han, J, Warkiani, ME & Song, Y-A 2018, 'High-throughput sorting of eggs for synchronization of C. elegans in a microfluidic spiral chip', LAB ON A CHIP, vol. 18, no. 4, pp. 679-687.View/Download from: Publisher's site
Stefen, H, Hassanzadeh-Barforoushi, A, Brettle, M, Fok, S, Suchowerska, AK, Tedla, N, Barber, T, Warkiani, ME & Fath, T 2018, 'A Novel Microfluidic Device-Based Neurite Outgrowth Inhibition Assay Reveals the Neurite Outgrowth-Promoting Activity of Tropomyosin Tpm3.1 in Hippocampal Neurons', Cellular and Molecular Neurobiology, vol. 38, no. 8, pp. 1557-1563.View/Download from: Publisher's site
© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Overcoming neurite inhibition is integral for restoring neuronal connectivity after CNS injury. Actin dynamics are critical for neurite growth cone formation and extension. The tropomyosin family of proteins is a regarded as master regulator of actin dynamics. This study investigates tropomyosin isoform 3.1 (Tpm3.1) as a potential candidate for overcoming an inhibitory substrate, as it is known to influence neurite branching and outgrowth. We designed a microfluidic device that enables neurons to be grown adjacent to an inhibitory substrate, Nogo-66. Results show that neurons, overexpressing hTpm3.1, have an increased propensity to overcome Nogo-66 inhibition. We propose Tpm3.1 as a potential target for promoting neurite growth in an inhibitory environment in the central nervous system.
Syed, MS, Rafeie, M, Vandamme, D, Asadnia, M, Henderson, R, Taylor, RA & Warkiani, ME 2018, 'Selective separation of microalgae cells using inertial microfluidics', BIORESOURCE TECHNOLOGY, vol. 252, pp. 91-99.View/Download from: Publisher's site
Tavassoli, H, Alhosseini, SN, Tay, A, Chan, PPY, Weng Oh, SK & Warkiani, ME 2018, 'Large-scale production of stem cells utilizing microcarriers: A biomaterials engineering perspective from academic research to commercialized products', Biomaterials, vol. 181, pp. 333-346.View/Download from: Publisher's site
© 2018 Elsevier Ltd Human stem cells, including pluripotent, embryonic and mesenchymal, stem cells play pivotal roles in cell-based therapies. Over the past decades, various methods for expansion and differentiation of stem cells have been developed to satisfy the burgeoning clinical demands. One of the most widely endorsed technologies for producing large cell quantities is using microcarriers (MCs) in bioreactor culture systems. In this review, we focus on microcarriers properties that can manipulate the expansion and fate of stem cells. Here, we provide an overview of commercially available MCs and focus on novel stimulus responsive MCs controlled by temperature, pH and field changes. Different features of MCs including composition, surface coating, morphology, geometry/size, surface functionalization, charge and mechanical properties, and their cellular effects are also highlighted. We then conclude with current challenges and outlook on this promising technology.
Tavassoli, H, Javadpour, J, Taheri, M, Mehrjou, M, Koushki, N, Arianpour, F, Majidi, M, Izadi-Mobarakeh, J, Negahdari, B, Chan, P, Warkiani, ME & Bonakdar, S 2018, 'Incorporation of Nanoalumina Improves Mechanical Properties and Osteogenesis of Hydroxyapatite Bioceramics', ACS BIOMATERIALS SCIENCE & ENGINEERING, vol. 4, no. 4, pp. 1324-1336.View/Download from: Publisher's site
Winter, M, Hardy, T, Rezaei, M, Nguyen, V, Zander-Fox, D, Ebrahimi Warkiani, M & Thierry, B 2018, 'Isolation of Circulating Fetal Trophoblasts Using Inertial Microfluidics for Noninvasive Prenatal Testing', Advanced Materials Technologies, vol. 3, no. 7.View/Download from: Publisher's site
© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim While noninvasive prenatal testing based on cell-free fetal DNA has recently revolutionized the field of aneuploidy screening in pregnancy, it remains limited to aneuploidy and microdeletion screening, and is unable to reliably detect single gene disorders. A number of recent studies have demonstrated the potential of circulating trophoblastic cells in providing cell-based noninvasive diagnosis with sequencing or array-based assays. However, considering the extreme rarity of these cells in blood, efficient, high-throughput, and clinically applicable enrichment technologies are yet to be developed. This study demonstrates for the first time the utility of inertial microfluidics for efficient isolation of trophoblastic cells from maternal peripheral blood. Under optimal operating conditions, high-recovery yields (79%) are obtained using a trophoblastic cell-line, which is subsequently confirmed with analysis of maternal blood. Feasibility of obtaining a diagnosis from cells isolated from a maternal sample is demonstrated in a case of confirmed fetal trisomy 21 in which six fetal cells are found in a 7 mL blood sample using fluorescence in situ hybridization. Finally, it is demonstrated that trophoblastic cells isolated using inertial microfluidics could be picked and subjected to a clinically validated sequencing assay, paving the way for further validation of this technology and larger clinical studies.
Alizadeh, A, Warkiani, ME & Wang, M 2017, 'Manipulating electrokinetic conductance of nanofluidic channel by varying inlet pH of solution', Microfluidics and Nanofluidics, vol. 21, no. 3, pp. 1-15.View/Download from: Publisher's site
© 2017, Springer-Verlag Berlin Heidelberg. The electrokinetic conductivity of micro-/nanofluidic systems, which strongly depends on the local solution properties (e.g., pH and ionic strength), has wide applications in nanosystems to control the system performance and ion rectification. Accurate and active manipulation of this parameter is proven to be very challenging since, in nanoscale, the ion transport is particularly dominated by the acquired surface charge on the solid–liquid interfaces. In this study, we propose an approach to manipulate the nanochannel electrokinetic conductivity by changing the pH value of the solution at the inlet in order to impose asymmetrical conditions inside nanochannel. The variable surface charge of walls is determined by considering the chemical adsorption on the solid–liquid interface and the electrical double layer interaction. The presented numerical model, which couples Poisson–Nernst–Planck and Navier–Stokes equations, can fully consider the electro-chemo-mechanical transport phenomena and predict the electrokinetic conductivity of nanofluidic channels with good accuracy. Modeling results show that the electrokinetic conductivity of the nanofluidic systems can be regulated by varying the solution pH at the inlet. It is revealed that the stronger electric double layers interaction can enhance the sensitivity of the nanochannel electrokinetic conductance to the inlet pH. This unique behavior of the nanochannel electrokinetic conductivity could broaden potential applications in biomedical, energy, and environmental systems using nanofluidic devices.
Asadnia, M, Ehteshami, SMM, Chan, SH & Warkiani, ME 2017, 'Development of a fiber-based membraneless hydrogen peroxide fuel cell', RSC Advances, vol. 7, no. 65, pp. 40755-40760.View/Download from: Publisher's site
© 2017 The Royal Society of Chemistry. In this paper, polyvinylidene fluoride (PVDF) nanofibers have been suggested as a viable substrate for flexible and implantable electrochemical devices. PVDF electrospun nanofibers exhibit excellent mechanical properties, flexibility, chemical stability, and biocompatibility, making them a potential option in the development of implant fuel cells. This paper presents a membraneless hydrogen peroxide fuel cell that is fabricated to demonstrate the possibility of using these nanofibers as the substrate for electrochemical devices. An open circuit potential of 0.65 V was achieved for the cell fabricated using Prussian Blue (PB) as the cathode material and nickel and aluminium as the anode materials. The power produced by the cell was ∼1 mW cm-2at 0.32 V. The results presented compare favourably with available power generators reviewed in the literature. Based on the proof of concept demonstration; PVDF electrospun nanofibers can be successfully used for implantable electrochemical devices such as bio-fuel cells and self-sustained point-of-care diagnostic systems.
© 2017 Mohsen Asadnia et al. By combining particle swarm optimization (PSO) and genetic algorithms (GA) this paper offers an innovative algorithm to train artificial neural networks (ANNs) for the purpose of calculating the experimental growth parameters of CNTs. The paper explores experimentally obtaining data to train ANNs, as a method to reduce simulation time while ensuring the precision of formal physics models. The results are compared with conventional particle swarm optimization based neural network (CPSONN) and Levenberg-Marquardt (LM) techniques. The results show that PSOGANN can be successfully utilized for modeling the experimental parameters that are critical for the growth of CNTs.
Aya-Bonilla, CA, Marsavela, G, Freeman, JB, Lomma, C, Frank, MH, Khattak, MA, Meniawy, TM, Millward, M, Warkiani, ME, Gray, ES & Ziman, M 2017, 'Isolation and detection of circulating tumour cells from metastatic melanoma patients using a slanted spiral microfluidic device', ONCOTARGET, vol. 8, no. 40, pp. 67355-67368.
Gerami, A, Armstrong, RT, Johnston, B, Warkiani, ME, Mosavat, N & Mostaghimi, P 2017, 'Coal-on-a-Chip: Visualizing Flow in Coal Fractures', Energy and Fuels, vol. 31, no. 10, pp. 10393-10403.View/Download from: Publisher's site
© 2017 American Chemical Society. Geomaterial microfluidics are the next generation of tools necessary for studying fluid flows related to subsurface engineering technologies. Traditional microfluidic devices do not capture surface wettability and roughness parameters that can have a significant influence on porous media flows. This is particularly important for coal seam gas reservoirs in which methane gas is transported through a well-developed system of natural fractures that display unique wettability and roughness characteristics. A coal geomaterial microfluidic device can be generated by etching a fracture pattern on a coal surface by using three-dimensional laser micromachining; however, it is unclear if the resulting surface properties are representative of real coal. In an effort to generate a realistic coal microfluidic device, we characterize coal surface roughness properties from real coal cleats. We then compare these results to the roughness of the patterns, generated from laser etching. Roughness measurements in real coal fractures show that cleats and microfractures are mostly oriented parallel to the coal beddings rather than perpendicular to the bedding, which is important when selecting coal for fabrication of a microfluidic device since we find that the natural microfractures influence the resulting roughness of etched fractures. We also compare resulting coal/brine/gas contact angles under static and dynamics conditions. The contact angle for coal is highly heterogeneous. Surface roughness and pore pressure may influence the contact angle. With the aid of the coal geomaterial device, the effect of these parameters on coal wettability can be explored and a range of possible coal contact angles can be visualized and represented. The geomaterial fabrication, as outlined herein, provides a tool to capture more realistic coal surface properties in microfluidics experiments.
Kulasinghe, A, Perry, C, Kenny, L, Warkiani, ME, Nelson, C & Punyadeera, C 2017, 'PD-L1 expressing circulating tumour cells in head and neck cancers.', BMC Cancer, vol. 17, no. 1, pp. 1-6.View/Download from: Publisher's site
Blockade of the PD-1/PD-L1 immune checkpoint pathway is emerging as a promising immunotherapeutic approach for the management and treatment of head and neck cancer patients who do not respond to 1st/2nd line therapy. However, as checkpoint inhibitors are cost intensive, identifying patients who would most likely benefit from anti PD-L1 therapy is required. Developing a non-invasive technique would be of major benefit to the patient and to the health care system.We report the case of a 56 year old man affected by a supraglottic squamous cell carcinoma (SCC). A CT scan showed a 20 mm right jugulodigastric node and suspicious lung lesions. The lung lesion was biopsied and confirmed to be consistent with SCC. The patient was offered palliative chemotherapy. At the time of presentation, a blood sample was taken for circulating tumour cell (CTC) analysis. The dissemination of cancer was confirmed by the detection of CTCs in the peripheral blood of the patient, measured by the CellSearch System (Janssen Diagnostics). Using marker-independent, low-shear spiral microfluidic technology combined with immunocytochemistry, CTC clusters were found in this patient at the same time point, expressing PD-L1.This report highlights the potential use of CTCs to identify patients which might respond to anti PD-L1 therapy.
Kulasinghe, A, Tran, THP, Blick, T, O'Byrne, K, Thompson, EW, Warkiani, ME, Nelson, C, Kenny, L & Punyadeera, C 2017, 'Enrichment of circulating head and neck tumour cells using spiral microfluidic technology', Scientific Reports, vol. 7, pp. 1-10.View/Download from: Publisher's site
© 2017 The Author(s). Whilst locoregional control of head and neck cancers (HNCs) has improved over the last four decades, long-term survival has remained largely unchanged. A possible reason for this is that the rate of distant metastasis has not changed. Such disseminated disease is reflected in measurable levels of cancer cells in the blood of HNC patients, referred to as circulating tumour cells (CTCs). Numerous marker-independent techniques have been developed for CTC isolation and detection. Recently, microfluidics-based platforms have come to the fore to avoid molecular bias. In this pilot, proof of concept study, we evaluated the use of the spiral microfluidic chip for CTC enrichment and subsequent detection in HNC patients. CTCs were detected in 13/24 (54%) HNC patients, representing both early to late stages of disease. Importantly, in 7/13 CTC-positive patients, CTC clusters were observed. This is the first study to use spiral microfluidics technology for CTC enrichment in HNC.
Kwon, T, Prentice, H, Oliveira, JD, Madziva, N, Warkiani, ME, Hamel, J-FP & Han, J 2017, 'Microfluidic Cell Retention Device for Perfusion of Mammalian Suspension Culture.', Scientific Reports, vol. 7, no. 1, pp. 1-11.View/Download from: Publisher's site
Continuous production of biologics, a growing trend in the biopharmaceutical industry, requires a reliable and efficient cell retention device that also maintains cell viability. Current filtration methods, such as tangential flow filtration using hollow-fiber membranes, suffer from membrane fouling, leading to significant reliability and productivity issues such as low cell viability, product retention, and an increased contamination risk associated with filter replacement. We introduce a novel cell retention device based on inertial sorting for perfusion culture of suspended mammalian cells. The device was characterized in terms of cell retention capacity, biocompatibility, scalability, and long-term reliability. This technology was demonstrated using a high concentration (>20 million cells/mL) perfusion culture of an IgG1-producing Chinese hamster ovary (CHO) cell line for 18-25 days. The device demonstrated reliable and clog-free cell retention, high IgG1 recovery (>99%) and cell viability (>97%). Lab-scale perfusion cultures (350 mL) were used to demonstrate the technology, which can be scaled-out with parallel devices to enable larger scale operation. The new cell retention device is thus ideal for rapid perfusion process development in a biomanufacturing workflow.
Rafeie, M, Welleweerd, M, Hassanzadeh-Barforoushi, A, Asadnia, M, Olthuis, W & Warkiani, ME 2017, 'An easily fabricated three-dimensional threaded lemniscate-shaped micromixer for a wide range of flow rates', Biomicrofluidics, vol. 11, no. 1, pp. 1-15.View/Download from: Publisher's site
Mixing fluid samples or reactants is a paramount function in the fields of micro total analysis system (μTAS) and microchemical processing. However, rapid and efficient fluid mixing is difficult to achieve inside microchannels because of the difficulty of diffusive mass transfer in the laminar regime of the typical microfluidic flows. It has been well recorded that the mixing efficiency can be boosted by migrating from two-dimensional (2D) to three-dimensional (3D) geometries. Although several 3D chaotic mixers have been designed, most of them offer a high mixing efficiency only in a very limited range of Reynolds numbers (Re). In this work, we developed a 3D fine-threaded lemniscate-shaped micromixer whose maximum numerical and empirical efficiency is around 97% and 93%, respectively, and maintains its high performance (i.e., >90%) over a wide range of 1
Ramalingam, N, Warkiani, ME & Hai-Qing Gong, T 2017, 'Acetylated bovine serum albumin differentially inhibits polymerase chain reaction in microdevices', Biomicrofluidics, vol. 11, no. 3, pp. 1-7.View/Download from: Publisher's site
Bovine serum albumin (BSA) is widely used as an additive in polymerase chain reaction (PCR)-based microfluidic devices to passivate reactors and alleviate nucleic-acid amplification. BSA is available commercially in two types: either acetylated or non-acetylated. A survey of literature indicates that both types of BSA are used in PCR-based microfluidic devices. Our study results reveal that the use of acetylated BSA in PCR micro-devices leads to differential inhibition of PCR, compared to non-acetylated BSA. This result is noticed for the first time, and the differential inhibition generally goes un-noticed, as compared to complete PCR inhibition.
Razmjou, A, Asadnia, M, Ghaebi, O, Yang, HC, Ebrahimi Warkiani, M, Hou, J & Chen, V 2017, 'Preparation of Iridescent 2D Photonic Crystals by Using a Mussel-Inspired Spatial Patterning of ZIF-8 with Potential Applications in Optical Switch and Chemical Sensor', ACS Applied Materials and Interfaces, vol. 9, no. 43, pp. 38076-38080.View/Download from: Publisher's site
© 2017 American Chemical Society. In this work, spatial patterning of a thin, dense, zeolitic imidazolate framework (ZIF-8) pattern was generated using photolithography and nanoscale (60 nm) dopamine coating. A bioinspired, unique, reversible, two-color iridescent pattern can be easily obtained for potential applications in sensing and photonics.
Sengupta, D, Kottapalli, AGP, Chen, SH, Miao, JM, Kwok, CY, Triantafyllou, MS, Warkiani, ME & Asadnia, M 2017, 'Characterization of single polyvinylidene fluoride (PVDF) nanofiber for flow sensing applications', AIP Advances, vol. 7, no. 10, pp. 1-8.View/Download from: Publisher's site
© 2017 Author(s). The use of Polyvinylidene Fluoride (PVDF) based piezoelectric nanofibers for sensing and actuation has been reported widely in the past. However, in most cases, PVDF piezoelectric nanofiber mats have been used for sensing applications. This work fundamentally characterizes a single electrospun PVDF nanofiber and demonstrates its application as a sensing element for nanoelectromechanical sensors (NEMS). PVDF nanofiber mats were spun by far field electrospinning (FFES) process and complete material characterization was conducted by means of scanning electron microscope (SEM) imaging, Raman Spectroscopy and FTIR spectroscopy. An optimized recipe was developed for spinning a single suspended nanofiber on a specially designed MEMS substrate which allows the nano-mechanical and electrical characterization of a single PVDF nanofiber. Electrical characterization is conducted using a single suspended nanofiber to determine the piezoelectric coefficient (d33) of the nanofiber to be -58.77 pm/V. Also the mechanical characterization conducted using a nanoindenter revealed a Young's Modulus and hardness of 2.2 GPa and 0.1 GPa respectively. Finally, an application that utilizes the single PVDF nanofiber as a sensing element to form a NEMS flow sensor is demonstrated. The single nanofiber flow sensor is tested in presence of various oscillatory flow conditions.
Shirani, E, Razmjou, A, Tavassoli, H, Landarani-Isfahani, A, Rezaei, S, Abbasi Kajani, A, Asadnia, M, Hou, J & Ebrahimi Warkiani, M 2017, 'Strategically Designing a Pumpless Microfluidic Device on an "inert" Polypropylene Substrate with Potential Application in Biosensing and Diagnostics', Langmuir, vol. 33, no. 22, pp. 5565-5576.View/Download from: Publisher's site
© 2017 American Chemical Society. This study is an attempt to make a step forward to implement the very immature concept of pumpless transportation of liquid into a real miniaturized device or lab-on-chip (LOC) on a plastic substrate. "Inert" plastic materials such as polypropylene (PP) are used in a variety of biomedical applications but their surface engineering is very challenging. Here, it was demonstrated that with a facile innovative wettability patterning route using fluorosilanized UV-independent TiO 2 nanoparticle coating it is possible to create wedge-shaped open microfluidic tracks on inert solid surfaces for low-cost biomedical devices (lab-on-plastic). For the future miniaturization and integration of the tracks into a device, a variety of characterization techniques were used to not only systematically study the surface patterning chemistry and topography but also to have a clear knowledge of its biological interactions and performance. The effect of such surface architecture on the biological performance was studied in terms of static/dynamic protein (bovine serum albumin) adsorption, bacterial (Staphylococcus aureus and Staphylococcus epidermidis) adhesion, cell viability (using HeLa and MCF-7 cancer cell lines as well as noncancerous human fibroblast cells), and cell patterning (Murine embryonic fibroblasts). Strategies are discussed for incorporating such a confined track into a diagnostic device in which its sensing portion is based on protein, microorganism, or cells. Finally, for the proof-of-principle of biosensing application, the well-known high-affinity molecular couple of BSA-antiBSA as a biological model was employed.
Syed, MS, Rafeie, M, Henderson, R, Vandamme, D, Asadnia, M & Warkiani, ME 2017, 'A 3D-printed mini-hydrocyclone for high throughput particle separation: application to primary harvesting of microalgae', LAB ON A CHIP, vol. 17, no. 14, pp. 2459-2469.View/Download from: Publisher's site
Asadnia, M, Kottapalli, AGP, Karavitaki, KD, Warkiani, ME, Miao, J, Corey, DP & Triantafyllou, M 2016, 'From Biological Cilia to Artificial Flow Sensors: Biomimetic Soft Polymer Nanosensors with High Sensing Performance', SCIENTIFIC REPORTS, vol. 6.View/Download from: Publisher's site
Hassanzadeh-Barforoushi, A, Shemesh, J, Farbehi, N, Asadnia, M, Yeoh, GH, Harvey, RP, Nordon, RE & Warkiani, ME 2016, 'A rapid co-culture stamping device for studying intercellular communication', SCIENTIFIC REPORTS, vol. 6.View/Download from: Publisher's site
Hesari, Z, Soleimani, M, Atyabi, F, Sharifdini, M, Nadri, S, Warkiani, ME, Zare, M & Dinarvand, R 2016, 'A hybrid microfluidic system for regulation of neural differentiation in induced pluripotent stem cells', JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A, vol. 104, no. 6, pp. 1534-1543.View/Download from: Publisher's site
Khoo, BL, Chaudhuri, PK, Ramalingam, N, Tan, DSW, Lim, CT & Warkiani, ME 2016, 'Single-cell profiling approaches to probing tumor heterogeneity', INTERNATIONAL JOURNAL OF CANCER, vol. 139, no. 2, pp. 243-255.View/Download from: Publisher's site
Kulasinghe, A, Perry, C, Warkiani, ME, Blick, T, Davies, A, O'Byrne, K, Thompson, EW, Nelson, CC, Vela, I & Punyadeera, C 2016, 'Short term ex-vivo expansion of circulating head and neck tumour cells', ONCOTARGET, vol. 7, no. 37, pp. 60101-60109.View/Download from: Publisher's site
Pavesi, A, Adriani, G, Tay, A, Warkiani, ME, Yeap, WH, Wong, SC & Kamm, RD 2016, 'Engineering a 3D microfluidic culture platform for tumor-treating field application', SCIENTIFIC REPORTS, vol. 6.View/Download from: Publisher's site
Rafeie, M, Zhang, J, Asadnia, M, Li, W & Warkiani, ME 2016, 'Multiplexing slanted spiral microchannels for ultra-fast blood plasma separation', LAB ON A CHIP, vol. 16, no. 15, pp. 2791-2802.View/Download from: Publisher's site
Ramalingam, N, Warkiani, ME, Ramalingam, N, Keshavarzi, G, Liu, H-B & Hai-Qing, TG 2016, 'Numerical and experimental study of capillary-driven flow of PCR solution in hybrid hydrophobic microfluidic networks', BIOMEDICAL MICRODEVICES, vol. 18, no. 4.View/Download from: Publisher's site
Tay, A, Pavesi, A, Yazdi, SR, Lim, CT & Warkiani, ME 2016, 'Advances in microfluidics in combating infectious diseases', BIOTECHNOLOGY ADVANCES, vol. 34, no. 4, pp. 404-421.View/Download from: Publisher's site
Warkiani, ME, Khoo, BL, Wu, L, Tay, AKP, Bhagat, AAS, Han, J & Lim, CT 2016, 'Ultra-fast, label-free isolation of circulating tumor cells from blood using spiral microfluidics', NATURE PROTOCOLS, vol. 11, no. 1, pp. 134-148.View/Download from: Publisher's site
Zarepour, E, Hassan, M, Chou, CT & Warkiani, ME 2016, 'Characterizing terahertz channels for monitoring human lungs with wireless nanosensor networks', NANO COMMUNICATION NETWORKS, vol. 9, pp. 43-57.View/Download from: Publisher's site
Zhang, J, Yan, S, Yuan, D, Alici, G, Nam-Trung, N, Warkiani, ME & Li, W 2016, 'Fundamentals and applications of inertial microfluidics: a review', LAB ON A CHIP, vol. 16, no. 1, pp. 10-34.View/Download from: Publisher's site
Asadnia, M, Kottapalli, AGP, Miao, J, Warkiani, ME & Triantafyllou, MS 2015, 'Artificial fish skin of self-powered micro-electromechanical systems hair cells for sensing hydrodynamic flow phenomena', JOURNAL OF THE ROYAL SOCIETY INTERFACE, vol. 12, no. 111.View/Download from: Publisher's site
Jing, T, Ramji, R, Warkiani, ME, Han, J, Lim, CT & Chen, C-H 2015, 'Jetting microfluidics with size-sorting capability for single-cell protease detection', BIOSENSORS & BIOELECTRONICS, vol. 66, pp. 19-23.View/Download from: Publisher's site
Khoo, BL, Lee, SC, Kumar, P, Tan, TZ, Warkiani, ME, Ow, SGW, Nandi, S, Lim, CT & Thiery, JP 2015, 'Short-term expansion of breast circulating cancer cells predicts response to anti-cancer therapy', ONCOTARGET, vol. 6, no. 17, pp. 15578-15593.
Shemesh, J, Jalilian, I, Shi, A, Yeoh, GH, Tate, MLK & Warkiani, ME 2015, 'Flow-induced stress on adherent cells in microfluidic devices', LAB ON A CHIP, vol. 15, no. 21, pp. 4114-4127.View/Download from: Publisher's site
Warkiani, ME, Wicaksana, F, Fane, AG & Gong, H-Q 2015, 'Investigation of membrane fouling at the microscale using isopore filters', MICROFLUIDICS AND NANOFLUIDICS, vol. 19, no. 2, pp. 307-315.View/Download from: Publisher's site
Khoo, BL, Warkiani, ME, Tan, DSW, Bhagat, AAS & Irwin, D 2014, 'Erratum: Clinical validation of an ultra high-throughput spiral microfluidics for the detection and enrichment of viable circulating tumor cells (PLoS ONE 9(7) e99409). doi:10.1371/journal.pone.0099409', PLoS ONE, vol. 9, no. 10.
Khoo, BL, Warkiani, ME, Tan, DS-W, Bhagat, AAS, Irwin, D, Lau, DP, Lim, AST, Lim, KH, Krisna, SS, Lim, W-T, Yap, YS, Lee, SC, Soo, RA, Han, J & Lim, CT 2014, 'Clinical Validation of an Ultra High-Throughput Spiral Microfluidics for the Detection and Enrichment of Viable Circulating Tumor Cells', PLOS ONE, vol. 9, no. 7.View/Download from: Publisher's site
Warkiani, ME, Guan, G, Luan, KB, Lee, WC, Bhagat, AAS, Chaudhuri, PK, Tan, DS-W, Lim, WT, Lee, SC, Chen, PCY, Lim, CT & Han, J 2014, 'Slanted spiral microfluidics for the ultra-fast, label-free isolation of circulating tumor cells', LAB ON A CHIP, vol. 14, no. 1, pp. 128-137.View/Download from: Publisher's site
Warkiani, ME, Khoo, BL, Tan, DS-W, Bhagat, AAS, Lim, W-T, Yap, YS, Lee, SC, Soo, RA, Han, J & Lim, CT 2014, 'An ultra-high-throughput spiral microfluidic biochip for the enrichment of circulating tumor cells', ANALYST, vol. 139, no. 13, pp. 3245-3255.View/Download from: Publisher's site
Hou, HW, Warkiani, ME, Khoo, BL, Li, ZR, Soo, RA, Tan, DS-W, Lim, W-T, Han, J, Bhagat, AAS & Lim, CT 2013, 'Isolation and retrieval of circulating tumor cells using centrifugal forces', SCIENTIFIC REPORTS, vol. 3.View/Download from: Publisher's site
Warkiani, ME, Lou, C-P, Liu, H-B & Gong, H-Q 2012, 'A high-flux isopore micro-fabricated membrane for effective concentration and recovering of waterborne pathogens', BIOMEDICAL MICRODEVICES, vol. 14, no. 4, pp. 669-677.View/Download from: Publisher's site
Warkiani, ME, Chen, L, Lou, C-P, Liu, H-B, Zhang, R & Gong, H-Q 2011, 'Capturing and recovering of Cryptosporidium parvum oocysts with polymeric micro-fabricated filter', JOURNAL OF MEMBRANE SCIENCE, vol. 369, no. 1-2, pp. 560-568.View/Download from: Publisher's site
Warkiani, ME, Lou, C-P & Gong, H-Q 2011, 'Fabrication and characterization of a microporous polymeric micro-filter for isolation of Cryptosporidium parvum oocysts', JOURNAL OF MICROMECHANICS AND MICROENGINEERING, vol. 21, no. 3.View/Download from: Publisher's site
Warkiani, ME, Lou, C-P & Gong, H-Q 2011, 'Fabrication of multi-layer polymeric micro-sieve having narrow slot pores with conventional ultraviolet-lithography and micro-fabrication techniques', BIOMICROFLUIDICS, vol. 5, no. 3.View/Download from: Publisher's site
Chen, L, Warkiani, ME, Liu, HB & Gong, HQ 2010, 'Polymeric micro-filter manufactured by a dissolving mold technique', Journal of Micromechanics and Microengineering, vol. 20, no. 7.View/Download from: Publisher's site
For filtration applications, we developed a process involving a 'dissolving mold technique' to fabricate polymeric filter membranes which have high aspect ratio pores with narrow pore size distribution. The dissolving mold technique has some advantages over the existing membrane microfabrication methods. Firstly, it resolves thoroughly the demolding problem by dissolving an interim polymer pillar mold, and secondly, it solves the membrane-folding (curling) problem upon releasing the membrane from the mold by integrating a support mesh bonding layer before dissolving of the interim pillar mold. This process is capable of fabricating filter membranes having micrometer and potentially nanometer pore sizes. The fabricated membranes have good mechanical properties, high porosity, smooth surface and uniform pore size distribution. © 2010 IOP Publishing Ltd.
Teymourtash, AR & Ebrahimi Warkiani, M 2009, 'Natural convection over a non-isothermal vertical flat plate in supercritical fluids', Scientia Iranica, vol. 16, no. 6 B, pp. 470-478.
In many applications, convection heat transfer is coupled with conduction and radiation heat transfer, which generate temperature gradients along the walls and may greatly affect natural convection heat transfer. The main objective of this study is to calculate the heat-transfer characteristics for natural convection from a non-isothermal vertical flat plate into a supercritical fluid. The influence of the non-uniformity of wall temperature on the heat transfer by natural convection along a vertical plate, having a linearly distributed temperature (characterized by the slope S) is also investigated. The thermal expansion coefficient is considered as a function of the temperature, the pressure, the van der Waals constants and the compressibility factor. The trends of the curves obtained with this equation and with values from tables of thermodynamic properties were similar and diverged at a critical point. These features confirmed the validity of this equation. Then, the governing systems of partial differential equations are solved numerically using the finite difference method. The local Nusselt number was then calculated and plotted as a function of the local Rayleigh number. It was observed that a positive slope of temperature distribution increases the heat transfer rate and a negative slope decreases it. © Sharif University of Technology, December 2009.
Teymourtash, AR & Warkiani, ME 2009, 'Natural Convection over a Non-Isothermal Vertical Flat Plate in Supercritical Fluids', SCIENTIA IRANICA TRANSACTION B-MECHANICAL ENGINEERING, vol. 16, no. 6, pp. 470-478.
Kulasinghe, A, Ebrahimi Warkiani, M & Punyadeera, C 2019, 'The Isolation and Characterization of Circulating Tumor Cells from Head and Neck Cancer Patient Blood Samples Using Spiral Microfluidic Technology.', pp. 129-136.View/Download from: Publisher's site
Metastasis is responsible for 90% of cancer-related deaths. The study of circulating tumor cells (CTCs) enables the study of the units of disease responsible for the process of metastasis. While the biology of the primary tissue is relatively known, little is understood about the cells en route to distant sites. Here we describe the isolation of CTCs using the spiral microfluidic technology for the efficient sorting of CTCs from head and neck cancer (HNC) patient blood samples. Furthermore, the molecular characterization of CTCs can aid in stratifying patients for targeted therapy such as immunotherapy, which is having a profound impact in the treatment of metastatic HNC.
Tay, AKP, Khoo, BL & Warkiani, ME 2018, 'Microfluidics for fast and frugal diagnosis of malaria, sepsis, and HIV/AIDS' in Frugal Innovation in Bioengineering for the Detection of Infectious Diseases, Springer, Switzerland, pp. 57-75.View/Download from: Publisher's site
© Springer International Publishing AG 2018. Rapid diagnosis of infectious diseases is necessary for timely treatment and to control spread of diseases. Conventional laboratory approaches are often labor-intensive and associated with time delays that are unacceptable in medical practice. Recent advances in micro-/nanotechnologies have facilitated the development of low-cost microfluidic devices with high sensitivity and throughput that can help reduce healthcare costs and pave the way toward personalized therapy. This chapter covers recent advances in point-of-care (POC) technologies with an emphasis on demonstrated and commercially available systems for diagnosis and treatment of malaria, sepsis, and human immunodeficiency virus (HIV) infection/acquired immune deficiency syndrome (AIDS). The current challenges to practical implementation of these technologies are discussed together with some future perspectives.
Pandya, HJ, Draz, MS, Warkiani, ME & Shafiee, H 2017, 'Rapid diagnosis of infectious diseases using microfluidic systems' in Diagnostic Devices with Microfluidics, pp. 145-161.View/Download from: Publisher's site
© 2017 by Taylor & Francis Group, LLC. Infectious diseases remain the primary public health challenge in many countries. Every year, infectious diseases account for more than 13 million deaths around the world, and for 30% of the total burden of disease. Developing countries are especially challenged with infectious diseases. According to world health organization (WHO), 50% of the total deaths in developing countries are attributed to various infections, including respiratory tract infections, diarrheal diseases, human immunodeficiency virus (HIV), tuberculosis, and malaria. In the healthcare system, a diagnostic cycle consists of several time-consuming steps besides sample transportation, pre-and postanalytical phases, result transmission, and batching practices augmenting the turnaround time from disease interpretation to results (Figure 7.1) [1-3]. The downside of experience-based empiric therapy management involves the choice of inappropriate antibiotherapy or late initiation of treatment often resulting in treatment failure [4-7].
Sofela, S, Sahloul, S, Kwon, T, Han, J, Warkiani, ME & Song, YA 2020, 'Synchronization of C. Elegans through high-throughput separation of eggs in a spiral microfluidic chip', 21st International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2017, pp. 1100-1101.
© 17CBMS-0001. In this work, we report a high-throughput sorting of C. elegans embryos from a mixed-age worm population in a spiral microfluidic chip for synchronization. Using inertial forces in the spiral chip, C. elegans eggs could efficiently be focused along the inner channel wall and separated out with high sorting efficiency and purity.
Syed, MS, Rafeie, M, Vandamme, D, Henderson, R & Warkiani, ME 2020, 'Selective separation of microalgae cells using inertial microfluidics', 21st International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2017, pp. 1375-1376.
© 17CBMS-0001. Microalgae are considered to be the most promising new source of biomass to meet world's growing demands. However, microalgal cultures are often contaminated, by bacteria or invading diatoms. The invasion of diatoms in a cell culture results in an overall decrease of biomass productivity and quality. This work demonstrates the application of inertial microfluidics for the selective separation and sorting of green microalgae cells from diatoms to obtain monocultures, at optimum conditions.
Ebrahimi Warkiani, M, Moloudi, R, Oh, S & Naing, MW 2019, 'INERTIAL-BASED MICROCARRIER-CELL RETENTION IN BIOPROCESSING', CYTOTHERAPY, ELSEVIER SCI LTD, Australia, pp. E4-E5.View/Download from: Publisher's site
Du, F, Rafeie, M, Warkiani, ME & Barber, T 2018, 'A systematic investigation of 3D-printed micromixers, applied to red blood cell lysis', 22nd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2018, pp. 2124-2126.
Copyright © (2018) by Chemical and Biological Microsystems Society. All rights reserved. Micromixer, mixing fluid samples or reactants, is an important microfluidic device that can be applied in the fields of micro total analysis system and biomedical applications. In this paper, 3D micromixers featured with various mixing strategies are designed, simulated and fabricated with the cost-effective wax printing. Experiments are made to validate the simulation results. Using the best performed micromixer, the lysis of red blood cell is conducted. The results presented here demonstrate a systematic method of optimizing the structure of 3D micromixers by integrating different mixing units.
Kottapalli, AGP, Asadnia, M, Karavitaki, KD, Warkiani, ME, Miao, J, Corey, DP & Triantafyllou, M 2017, 'Engineering biomimetic hair bundle sensors for underwater sensing applications', AIP Conference Proceedings, Mechanics of Hearing Workshop, AIP, St Catharines, Canada, pp. 160003-1-160003-7.View/Download from: Publisher's site
© 2018 Author(s). We present the fabrication of an artificial MEMS hair bundle sensor designed to approximate the structural and functional principles of the flow-sensing bundles found in fish neuromast hair cells. The sensor consists of micro-pillars of graded height connected with piezoelectric nanofiber "tip-links" and encapsulated by a hydrogel cupula-like structure. Fluid drag force actuates the hydrogel cupula and deflects the micro-pillar bundle, stretching the nanofibers and generating electric charges. These biomimetic sensors achieve an ultrahigh sensitivity of 0.286 mV/(mm/s) and an extremely low threshold detection limit of 8.24 μm/s. A complete version of this paper has been published .
Kulasinghe, A, Perry, C, Kenny, L, Blick, T, Warkiani, M, Vela, I, O'Byrne, K, Thiery, J-P, Thompson, E, Nelson, C & Punyadeera, C 2018, 'Circulating tumor cells: The tumor trail left in the blood', CANCER RESEARCH, Annual Meeting of the American-Association-for-Cancer-Research (AACR), AMER ASSOC CANCER RESEARCH, Chicago, IL.View/Download from: Publisher's site
Moloudi, R, Oh, S, Yang, C, Teo, KL, Lam, ATL, Warkiani, ME & Naing, MW 2018, 'Separation of microcarriers from mesenchymal stem cell suspensions using inertial focusing', 22nd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2018, pp. 2082-2083.
Copyright © (2018) by Chemical and Biological Microsystems Society. All rights reserved. Rapidly evolving cell-based therapies in clinical trials demand alternative approaches for efficient expansion of adherent cell types such as human mesenchymal stem cells (hMSCs). Using microcarriers (MCs) suspended in a bioreactor provides a higher surface-to-volume ratio for cell culture. Following cell expansion and detachment from microcarriers, a novel approach which utilizes inertial focusing to separate MCs from the final cell suspensions is demonstrated.
Raoufi, MA, Mashhadian, A, Asadnia, M & Warkiani, ME 2018, 'Experimental and numerical study of viscoelasticity effects on particle focusing within a straight trapezoidal channel', 22nd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2018, pp. 468-471.
Copyright© (2018) by Chemical and Biological Microsystems Society.All rights reserved. This paper investigates the effect of viscoelastic force on the focusing behaviour of 5.1µm particles in a straight trapezoidal channel and elucidates fundamentals of elasto-inertial microfluidics dynamic using both experimental and computational approaches. To date, numerous studies have been conducted to improve particle sorting by altering microchannel structures, flow rates and properties of solutions; however, none of these studies have fundamentally investigated the effects of viscoelasticity on particle movements through microchannels with nonlinear cross-section. The results revealed that, at each cross section the inertial lift and elastic forces are unidirectional everywhere except around corners and the channel center which causes the particles to focus in these areas.
Alzahid, Y, Mostaghimi, P, Warkiani, ME, Armstrong, RT, Joekar-Niasar, V & Karadimitriou, N 2017, 'Alkaline surfactant polymer flooding: What happens at the pore scale?', Society of Petroleum Engineers - SPE Europec Featured at 79th EAGE Conference and Exhibition, pp. 386-402.View/Download from: Publisher's site
Copyright © 2017, Society of Petroleum Engineers. Alkaline-surfactant-polymer (ASP) flooding is a Chemical Enhanced Oil Recovery (CEOR) method whereby alkali, surfactant and polymer are injected as the same slug. It is one of the most promising worldwide focus of CEOR research and field trials, due to the unique synergy of the three chemical components. Polymers increase the viscosity of injected water, which improves macroscopic sweep efficiency by stabilizing the displacing front and counteracting heterogeneity effects. Surfactants, on the other hand, decrease the interfacial tension between the injected water and crude oil, which improves microscopic displacement efficiency by mobilizing trapped oil. Alkaline chemicals generate soap when reacting with crude oil, which reduces surfactant adsorption to grain surfaces. To fully understand the flow mechanisms in oil reservoirs and develop efficient recovery methods, it is essential to recognize the physics at the pore scale since this is the length scale at which capillary-trapped oil is mobilized. We developed an experimental micro-scale approach in which oil recovery is analyzed using microfluidics. The micromodels are fabricated based on: (1) a pore network generated via a Delaunay triangulation with an average pore size of 60 µm, (2) X-ray micro-Computed Tomography images of Bentheimer sandstone with resolution of 4.95 µm, and (3) a fractured network with a porosity of 10%. The networks are etched into silicon wafers and used to fabricate polydimethylsiloxane (PDMS) microfluidic devices. We compare not only oil recovery with ASP flooding between different porous networks but we also study displacement mechanisms and pore scale emulsion formation for ASP formulations that exhibit Winsor Type II+, II- and III behaviour. Our studies elucidate micro-scale oil recovery mechanisms for different ASP flooding scenarios. Our results provide direct visualization of the micro-scale phenomena occurring during ASP flooding...
Asadnia, M, Kottapalli, AGP, Warkiani, ME, Miao, JM & Triantafyllou, MS 2017, 'ENGINEERING MINIATURIZED HAIR CELL SENSORS FOR AUDITORY SYSTEM', 30TH IEEE INTERNATIONAL CONFERENCE ON MICRO ELECTRO MECHANICAL SYSTEMS (MEMS 2017), 30th IEEE International Conference on Micro Electro Mechanical Systems (MEMS), IEEE, Las Vegas, NV, pp. 1173-1176.
Ghorbani, S, Bazaz, SR, Warkiani, ME, Soleimani, M & Mehrizi, AA 2017, 'Evaluation of Nanofiber PLA Scaffolds Using Dry- and Wet-Electrospinning Methods', 2017 24TH NATIONAL AND 2ND INTERNATIONAL IRANIAN CONFERENCE ON BIOMEDICAL ENGINEERING (ICBME), 24th National Iranian Conference on Biomedical Engineering / 2nd International Iranian Conference on Biomedical Engineering (ICBME), IEEE, Tehran, IRAN, pp. 89-94.
Barforoushi, AH, Shemesh, J, Farbehi, N, Asadnia, M, Yeoh, GH, Nordon, RE & Warkiani, ME 2016, 'A rapid microfluidic stamping device for studying cardiac stem cells and endothelial cells co-culture', 20th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2016, pp. 1069-1070.
Many biological processes in the body are regulated by synchronized activity between two cell types. Recent advances in cell μcontact printing have facilitated the in-vitro study of homotypic and heterotypic cell-cell interaction. However, these techniques are still complicated to perform and are seldom used by biologists. We report here development of a novel microfluidic stamping device for patterning two adherent cell lines with well-defined interlacing configurations to study cell-cell spatial interactions. To demonstrate the stamp's capabilities, we developed an in-vitro model of endothelial and cardiac mesenchymal stem cell interactions, which are thought to regulate coronary repair after myocardial injury.
Rafeie, M, Zhang, J, Asadnia, M, Li, W & Warkiani, ME 2016, 'Multiplexing slanted spiral microchannels for ultra-fast blood plasma separation', 20th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2016, pp. 906-907.
The ability to efficiently fractionate blood into its individual components is crucial for therapeutic and diagnostic purposes. Here, we developed an inertial microfluidic system for cell focusing and blood plasma separation. First, polystyrene beads and blood cells were used to investigate the inertial focusing performance of a single slanted spiral microchannel as a function of particle size, flow rate, and the haematocrit (HCT) concentration. Next, we built a high-throughput system consisted of 16 interconnected spiral channels which can process diluted samples at 24 mL/min. The proposed multiplexed system surmounts shortcomings of previously-reported microfluidic systems concerning throughput, yield and operation efficiency.
Chung, C-Y, Warkiani, ME, Mesgari, S, Rosengarten, G & Taylor, R 2015, 'Thermoset polyester-based superhydrophobic microchannels for nanofluid heat transfer applications', MICRO+NANO MATERIALS, DEVICES, AND SYSTEMS, SPIE Conference on Micro+Nano Materials, Devices, and Systems, SPIE-INT SOC OPTICAL ENGINEERING, Sydney, AUSTRALIA.View/Download from: Publisher's site
Kwon, T, Madziva, N, Oliveira, JD, Chandramohan, SK, Yin, L, Prentice, H, Warkiani, ME, Hamel, JFP & Han, J 2015, 'Long-term steady state perfusion culture of mammalian cells using a robust microfluidic cell retention device', MicroTAS 2015 - 19th International Conference on Miniaturized Systems for Chemistry and Life Sciences, pp. 108-110.
© 15CBMS-0001. Cell retention devices are used to retain cells in containers during perfusion culture. However, the conventional membrane-based filtration devices have challenges such as membrane fouling/clogging and increased contamination risk due to frequent filter replacements. To solve these challenges, we introduce a new microfluidic cell retention device based on inertial cell focusing. We demonstrated a long-term steady state perfusion culture of suspended CHO cells, where high density of cells (> 3×106 cells/mL) and viability (> 90%) were maintained for more than a week. Our membrane-less and clog-free cell retention device has unique advantage over the conventional filtration devices for perfusion culture.
Shi, A, Shemesh, J, Asadnia, M, Robles, UA, Green, R, Yeoh, GH & Warkiani, ME 2015, 'A novel microfluidic patterning device for neuron-glia co-culture', MicroTAS 2015 - 19th International Conference on Miniaturized Systems for Chemistry and Life Sciences, pp. 633-635.
© 15CBMS-0001. Many biological processes in the body are regulated by synchronized activity between two cell types. To study cell-cell interactions, it is necessary to develop easy to use co-culture systems, where different cell types can be cultured within the same confined space. Designing a complete 3D biomimetic system to study these interactions in vitro requires complex protocols and use of non-conventional materials such as hydrogels. This paper reports development of a temporarily sealed microfluidic device which utilizes a novel valve design to directly and accurately co-culture two cell lines in alternating rows, allowing them to proliferate towards each other and then observe their interaction at the boundaries of their interface.
Zarepour, E, Hassan, M, Chou, CT, Adesina, AA & Warkiani, ME 2015, 'Reliability Analysis of Time-Varying Wireless Nanoscale Sensor Networks', 2015 IEEE 15TH INTERNATIONAL CONFERENCE ON NANOTECHNOLOGY (IEEE-NANO), IEEE NANO 2015 15th INTERNATIONAL CONFERENCE ON NANOTECHNOLOGY, IEEE, ROME, ITALY, pp. 63-68.
Zarepour, E, Hassan, N, Hassan, M, Chou, CT & Warkiani, ME 2015, 'Design and analysis of a wireless nanosensor network for monitoring human lung cells', BodyNets International Conference on Body Area Networks.View/Download from: Publisher's site
© 2015 ICST. Thanks to nanotechnology, it is now possible to fabricate sensor nodes below 100 nanometers in size. Although wireless communication at this scale has not been successfully demonstrated yet, simulations confirm that these sensor nodes would be able to communicate in the terahertz band using graphene as a transmission antenna. These developments suggest that deployment of wireless nanoscale sensor networks (WNSNs) inside human body could be a reality one day. In this paper, we design and analyse a WNSN for monitoring human lung cells. We find that respiration, i.e., the periodic inhalation and exhalation of oxygen and carbon dioxide, is the major process that inuences the terahertz channel inside lung cells. The channel is characterised as a two-state channel, where it periodically switches between good and bad states. Using real human respiratory data, we -nd that the channel absorbs terahertz signal much faster when it is in bad state compared to good state. Our simulation experiments confirm that we could reduce transmission power of the nanosensors, and hence the electromagnetic radiation inside lungs due to deployment of WNSN, by a factor of 20 if we could schedule all communication only during good channel states. We propose two duty cycling protocols along with a simple channel estimation algorithm that enables nanosensors to achieve such scheduling.
Khoo, BL, Warkiani, ME, Guan, G, Tan, DSW, Lim, AST, Lim, WT, Yap, YS, Lee, SC, Soo, RA, Han, J & Lim, CT 2014, 'Ultra-high throughput enrichment of viable circulating tumor cells', IFMBE Proceedings, pp. 1-4.View/Download from: Publisher's site
© Springer International Publishing Switzerland 2014. Detection, enumeration and characterization of rare circulating tumor cells (CTCs) from the peripheral blood of cancer patients potentially provide critical insights into tumor biology and is promising for cancer diagnosis and prognosis. Here, we present a novel multiplexed spiral microfluidic device for ultra-high throughput, label-free enrichment of CTCs from clinically relevant blood volumes. The fast processing time of the technique (7.5 mL blood in < 5 min) and high sensitivity of the device lends itself to a broad range of potential genomic and transcriptomic applications. The method can specifically separate and preserve all fractions of blood (i.e., plasma, CTCs and PBMC) for diverse downstream analysis. CTCs were detected from 100% (10/10) of blood samples collected from patients with advanced stage metastatic breast (12- 56 CTC/ml) or lung cancer (30-153 CTC/ml). Cancer cells were characterized with immunostaining and fluorescence in situ hybridization (FISH) (HER2/neu). Retrieved cells were unlabelled and hence more viable for propagation and other informative analysis such as the next generation sequencing (NGS) to guide treatment and individualized patient care.
© Springer International Publishing Switzerland 2014. Rapid and accurate detection of pathogenic bacteria in drinking-water systems is a challenging problem. Filtration based concentration techniques have been widely used for isolation and recovery of C. parvum and Giardia (oo)cysts into small volumes for downstream analysis. Micro-fabricated membranes that contain pores with the same size and shape have been shown to be a good choice for efficient pathogen removal. In this study, a robust isoporous membrane was fabricated and validated for concentration and recovery of C. parvum and Giardia (oo)cysts from tap-water according to the EPA standard protocol. Microfiltration results of the isoporous polymeric microfilter revealed that using a simple backflushing procedure, more than 90% of the C. parvum and Giardia (oo)cysts spiked in the tap-water samples can be recovered, showing greater performance than available commercial microfilters. This research demonstrated the potential application of micro-fabricated filters with regular pores for large-scale filtration and monitoring of C. parvum and Giardia (oo)cysts contamination in drinking-water distribution systems.
Warkiani, ME, Tay, AKP, Guan, G & Han, J 2014, 'Next-generation microfilter: Large scale, continuous mammalian cell retention for perfusion bioreactors', 18th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2014, pp. 2474-2476.
© 14CBMS. In this study, we report on the development of the first membrane-less, clog-free microfiltration platform for ultra-high throughput (up to 1000 mL/min) cell separation, using a massively-multiplexed array of inertial microfluidic cell sorting channels. Our developed system consists of multiple layer (10∼20) of PDMS sheets with embossed microchannels (i.e., ∼ 200 individual spirals) bonded together for continuous size-based cell sorting from a large volume of biological fluid. Subsequent perfusion culture experiments using the cell retention system show the potential to significantly enhance overall efficiency of perfusion cell culture.
Warkiani, ME, Tay, AKP, Khoo, BL, Xu, X, Lim, CT & Han, J 2014, 'Enabling reliable detection of low abundance malaria parasites from blood using inertial microfluidics', 18th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2014, pp. 1157-1159.
© 14CBMS. In this paper, a highly efficient inertial microfluidic device was described to enable the enrichment and purification of malaria parasites from blood, which leads to more reliable and specific PCR-based malaria detection. The device makes use of equilibrium between shear-modulated inertial lift and wall-induced lift forces to remove WBCs, thereby facilitating malaria parasite enrichment. The cascaded system is able to process 1 mL of lysed blood in 15 min, with the WBC depletion efficiency of 99.99% which is higher than any commercially available kit (i.e., CD-45 coated beads) for this purpose. Parasite densities ranging from 103 to 104 P. falciparum parasites per mL (∼ 2 per μL) have been quantified in whole blood using quantitative PCR. Obtained results revealed that the sample preparation using the inertial microfluidic device can significantly enhance the PCR results and make it more reliable by removing most of the unwanted genomic materials and PCR inhibitors.
Guan, G, Warkiani, ME, Luan, KB, Lim, CT, Chen, PCY & Han, J 2013, 'High throughput circulating tumor cell isolation using trapezoidal inertial microfluidics', 17th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2013, pp. 23-25.
A novel Dean coupled inertial microfluidic device with trapezoidal cross-section spiral channel for ultra-fast, label- free enrichment of circulating tumor cells (CTCs) from clinically relevant blood volumes is reported in this work. Using this single spiral microchannel with one inlet and two outlets, we have successfully isolated and recovered more than 80% of cancer cell line cells spiked in 7.5 mL of blood within 8 min with high purity. Putative CTCs were detected and isolated from 100% patient samples with advanced stage metastatic breast and lung cancer using standard biomarkers. DNA fluorescence in-situ hybridization (FISH) was also carried out to evaluate HER2 status in CTCs isolated from patient samples. Copyright © (2013) by the Chemical and Biological Microsystems Society All rights reserved.
Jing, T, Ramji, R, Warkiani, ME, Lim, CT, Han, J & Chen, CH 2013, 'High throughput single cancer cell encapsulation and self sorting for protease assay by using jetting microfluidics', 17th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2013, pp. 1373-1375.
In this work, a droplet microfluidic device integrated with droplet sorting function was presented for single cancer cell encapsulations and protease activity measurements. Individual cells were encapsulated into aqueous droplets at flow focusing junction under jetting conditions. Droplets with cells encapsulated inside are larger than other empty droplets, enabling effective droplet sorting through a deterministic lateral displacement micro-pillar design. All droplets with cells are therefore collected by an observation chamber for enzymatic activity monitoring. Here we focused on measuring matrix metalloproteinase (MMPs) secretion intensities at the individual cell level to obtain further insights into the malignant characteristics of these cells.
Warkiani, ME, Khoo, BL, Tan, DSW, Bhagat, AAS, Lim, WT, Han, J & Lim, CT 2013, 'Circulating tumor cell (CTC) enrichment: Ultra high throughput processing of clinically relevant blood volumes using a multiplexed spiral biochip', 17th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2013, pp. 1156-1158.
Detection and characterization of circulating tumor cells (CTCs) from minimally invasive "liquid biopsy" provides critical insights into tumor biology and is critical for companion diagnostics and care. Here, we present a multiplexed spiral biochip for ultra-high throughput isolation of CTCs using inertial microfluidics to realize a single step label-free enrichment process. This device is capable of efficient cell separation of clinically relevant blood volumes in a short period of time (7.5 mL blood in 35 min). CTCs were successfully detected and isolated from 100% (50/50) blood samples collected from patients with advanced stage metastatic breast and lung cancer. They were identified under immunofluorescence assays (cytokeratin positive), as well as molecular probes (EGFR or HER2 positive). CTC recovery rate ranges from 3-1535 CTCs/mL and obtained under high purity (1 CTC for every 30-100 white blood cells detected). Retrieved cells are unlabelled and hence more viable for propagation, drug development and other downstream analysis.
Warkiani, ME, Gong, H-Q & Fane, A 2011, 'Surface modification of micro/nano-fabricated filters', MATERIALS INTEGRATION, 2nd International Symposium on Advanced Synthesis and Processing Technology for Materials (ASPT2011)/8th Materials Science School for Young Scientists (KINKEN-WAKATE2011), TRANS TECH PUBLICATIONS LTD, Sendai, PEOPLES R CHINA, pp. 87-+.View/Download from: Publisher's site
Warkiani, ME, Gong, HQ, Fane, AG & Wicaksana, F 2011, 'Effects of Membrane Pore Morphology on Fouling Behavior of Polymeric Micro fabricated Membrane During Crossflow Micro-filtration', NANOTECHNOLOGY 2011: BIO SENSORS, INSTRUMENTS, MEDICAL, ENVIRONMENT AND ENERGY, NSTI-NANOTECH 2011, VOL 3, NSTI Nanotechnology Conference and Expo, CRC PRESS-TAYLOR & FRANCIS GROUP, Boston, MA, pp. 569-572.
Warkiani, ME, Gong, HQ, Fane, AG & Wicaksana, F 2011, 'Effects of Membrane Pore Morphology on Fouling Behavior of Polymeric Micro-fabricated Membrane During Crossflow Micro-filtration', CLEAN TECHNOLOGY 2011: BIOENERGY, RENEWABLES, STORAGE, GRID, WASTE AND SUSTAINABILITY, CTSI Clean Technology and Sustainable Industries Conference and Expo, Clean Technology 2011, CRC PRESS-TAYLOR & FRANCIS GROUP, Boston, MA, pp. 220-223.