Microfluidics and BioMEMS Laboratory

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Introduction to Microfluidics

Microfluidics is to study fluids in microscale. The field involves (1) microfabrication (to make devices containing microscale features), (2) microflows (to study fluids, e.g., pumping, valving, mixing, and simulation), and (3) applications.

Devices are fabricated using techniques similar to those used for fabricating computer chips. The techniques include film deposition, patterning (as in photolithography), etching, assembly, and others.  The process of making a thermoplastic device is illustrated in Figure 1.

 

Figure 1. The process to fabricate a plastic microfluidic device. (J. MEMS, 15, 2006, 1060)

 

Manipulation of fluids in a microfluidic device needs pumps, valves, and/or other components.  One of mechanisms suitable for pumping fluids in microdevices is electroosmosis (EO).  EO is generated in a microchannel filled with an appropriate solution when a voltage is applied across the channel. Syringe pumps are often used as well. Microvalves are another key component in a microfluidic device and they may regulate flows, contain fluids, and isolate one region from the other. 

Applications of microfluidics and BioMEMS devices include cell culture and analysis, clinical diagnostics, environmental monitoring, DNA and protein analysis, and biological warfare agent detection. Examples of extensive reviews on the topic include: Special issue in Nature, Vol 442, July 27, 2006, 367-418; Manz, et al. Analytical Chemistry 2010, 82, 4830–4847

Selected Research Projects in Dr. Fan's Lab

Pathogen Detection. The goal of this research is to develop low-cost and hand-held devices for pathogen detection at the point of care (or the point of need). The device integrates sample preparation steps with detection and the operation does not require laboratory equipment and power outlets. An example is illustrated in the device for Zika virus detection as described in the article published in Angewandte Chemie International Edition. The projects for detecting influenza virus, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), Dengue virus, and Escherichia coli, have been funded by National Institutes of Health (NIH), National Science Foundation (NSF), and University of Florida.

Flexible/Stretchable Electronics. The goal of this research is to develop tools and processes that are useful to the fabrication and characterization of flexible electronics. They include surface treatment, via fabrication, component attachment, and simulation. The background information can be found in the article published in Journal of Micromechanics and Microengineering. The project has been funded by National Science Foundation (NSF) and Jabil Inc. via the MIST center.

Circulating Tumor Cells (CTCs). The goal of this research is to develop microfluidic devices for isolating tumor cells circulating in peripheral blood. CTCs have been explored as biomarkers for cancer diagnosis and prognosis. However, CTCs are extremely rare, typically a few among billions of healthy blood cells.  Therefore, cell sorting and enrichment are required. The background information can be found in the book entitled "Circulating Tumor Cells: Isolation and Analysis". The project has been funded by National Cancer Institute (NCI), Florida Department of Health, McJunkin Family Charitable Foundation, and the University of Florida.

Paper Microfluidics. The goal is to develop low-cost, paper-based, rapid analytical devices for point-of-care applications. Laminated paper-based analytical devices (LPADs) are fabricated in a way similar to making an identification card; lamination with plastic sheets increases the mechanical strength and overall durability of a paper device. The background information can be found in the article published in Annual Review of Analytical Chemistry. A project in developing such a device for pathogen detection after an air sampler has been funded by National Science Foundation (NSF). A project in developing a point-of-care device for Zika virus detection has been funded by Florida Department of Health (FL DoH).

Microfluidic Valves. The goal is to develop thermally actuated and manufactuable microfluidic valves for a variety of applications. The valves can be integrated in a device; the actuation of valves will be controlled by a printed circuit board (PCB). The valves are expected to be useful in any system that needs flow controls. The background information can be found in the article published in Lab on a Chip. The project has been funded by Defense Advanced Research Projects Agency (DARPA), and a project for an immunoassay array involving a number of microvalves has been funded by National Institutes of Health (NIH).

Protein Synthesis Array. The goal is to develop a multiplexed, cell-free protein expression system for high-throughput protein production, so that the functional studies of proteins can be matched with gene-discovery in terms of the scale and throughput. The system consists of an array of microfluidic units and each unit functions as a microreactor to synthesize proteins corresponding to a gene of interest. The array can also be used for detecting biological warfare agents that inhibit protein synthesis such as ricin. The background information can be found in the article published in Biotechnology and Bioengineering. The project has been funded by DARPA, NIH, Covitect Inc., and Dasfanh Biosciences LLC.

Secondhand Smoke (SHS). The goal is to develop a hand-held analyzer for detecting SHS exposure. Child exposure to SHS is associated with sudden infant death syndrome, acute respiratory infections, ear problems, and childhood asthma. As a result, a hand-held analyzer will help diagnose a child with an asthma attack or severe ear infection whether SHS is causing the problem. The analyzer consists of components to enrich and detect biomarkers associated with tobacco smoke. The background information can be found in the article published in Analytical Chemistry. The project has been funded by Flight Attendant Medical Research Institute (FAMRI) and James and Esther King Biomedical Research Program of FL DoH.

2D Gel Chip. The goal is to design and fabricate a microfluidic device that provides an alternative approach to two-dimensional gel electrophoresis, which is extensively used in chemical and biological labs. The microfluidics-enabled method likely leads to rapid analysis, high separation resolution, improved protein identification accuracy, and enhanced reproducibility. The background information can be found in the article published in Lab on a Chip. The device could be used as a tool for biomarker discovery and screening. The project has been funded by Army Research Office and NIH.

Hydrogen Sensor. The goal is to develop a sensor for detecting possible leakage of hydrogen—the fuel of today's space vehicle and possibly tomorrow's automobiles. The sensor is based on an enzyme-catalyzed reaction, which can be carried out in a microfluidic device. Compared to the state-of-the-art, metal or alloy-based hydrogen gas sensors, the benefits include ambient temperature operation and enhanced selectivity over background gases. The background information can be found in the article published in Analytical Chemistry. The project has been funded by NSF and National Aeronautics and Space Administration (NASA).

Examples of Corporations Using Microfluidics

Agilent Technologies; Caliper Life Sciences (now PerkinElmer); Cepheid; Standard BioTools; Gyros; Microfluidic ChipShop; Dolomite, and the others.

Useful Links:

Several scientific journals are dedicated to the field, including Lab on a chip by Royal Society of Chemistry; Microfluidics and Nanofluidics by Springer; Biomicrofluidics by American Institute of Physics (AIP); and Journal of MEMS, by the Institute of Electrical and Electronics Engineers (IEEE) and American Society of Mechanical Engineers (ASME). Other scientific journals related to the filed include Analytical Chemistry, ACS Sensors, Sensors and Actuators B, Biosensors and Bioelectronics, Journal of Micromechanics and Microengineering, Microsystems & Nanoengineering, etc.

Check Chips & Tips for solutions to common practical problems encountered in the lab.

Many scientific conferences dedicated to the field, including µTAS, Transducers, Hilton Head Workshop, MEMS, Society for Laboratory Automation & Screening (SLAS) Meeting, Microtechnologies in Medicine and Biology, etc.