Research in our lab spans the areas of microfluidics, lab-on-chip, bioMEMS, and bioelectronics for medical applications. The common theme in our projects is instrumentation for obtaining diagnostic data from biological systems, from the level of molecules and cells (for example, digital assays) to the level of the individual (for example, wearable sensors). We are motivated by the premise that more data improves our understanding of life, and can help us make better decisions about our health and environment. Current projects involve two thrusts:
Modern biological research relies on high-throughput screening (HTS) instruments which can perform assays involving large numbers biomolecules or cells. These instruments must be able achieve high speed, low cost, and minimal reagent consumption. Particularly well suited for HTS is a class of microfluidic devices which utilizes water-in-oil droplets as chemical reaction containers. With typical dimensions of <100 micrometers and with volumes on the order of nanoliters to femtoliters, droplet systems have the potential to manage large libraries of chemical reactions while consuming minimal amounts of reagents. Droplet systems have been widely used for modern methods of digital PCR, single cell assays, chemical fractionation, and more. Our work in this area focuses on the physics and applications of multiphase flow and interfacial phenomena, the manipulation and storage of droplets, and label-free biodetection. Applications of these devices include digital assays, including single molecule, single cell, and single organism screening.
Microelectronics and microsensors have become pervasive in the modern age, creating a significant opportunity for their use in portable, wearable bioinstruments for distributed and home health monitoring. We are motivated by the use of these devices to help manage chronic disease, which accounts for >65% of US health care costs. Our work in this area takes a translational approach, focused on developing systems to serve needs in healthcare as well as environmental applications. Current projects include ultraminiature wearable biosensors for fitness and stress monitoring, portable biodetection systems for detecting invasive species in foreign vessels entering the Great Lakes, and multiplexed electronics for portable flow cytometry systems.
A. Vedhanayagam
In this project we perform rapid image-based flow cytometry utilizing GPU-Accelerated computer vision and machine learning. Our systems are designed to meet the throughput demands of liquid biopsy and environmental screening.
One of the rapidly growing applications of artificial intelligence and machine learning is using computer vision to classify biomedical images. In this project, we are utilizing (GPU) hardware-accelerated computer vision and neural networks to recognize and sort cancer cells in human blood, paving the way towards the so-called 'liquid biopsy' in cancer diagnostics. A modified version of the system can be used for rapid identification of environmental contaminants such as microplastics.
P. Weerappuli
We developed a scalable droplet random access memory (DRAM), a microfluidic device in which droplets and single cells can be addressably stored and released.
Single cell analysis methods rely on techniques to manipulate large populations of cells, once cell at a time. In this work, we designed a scalable microfluidic platform in which single cells can be stored and retrieved in a manner analogous to computer memory. A key enabling technology is a novel gas-on-gas multiplexing valve which can be patterned at densities of >1000 valves per device. This enables the control of n on-chip gas valves with log(n) external valves. We also designed a high density array of 10,000 single cell traps, each of which can be controlled independently.
M. Rezaei, A. Mandhare, A. Sunkari, N. Raitu, D. Ulmer, O. Sufi, A. Karaali
TRACE is a novel, earlobe-mounted heart rate monitor which provides beat-to-beat accuracy in fitness and health monitoring applications, based on our patented heart rate sensing method.
Wearable continuous heart rate monitors (CHRM) are widely used in fitness and health applications. The majority of existing devices are either wristwatches, which utilize photoplethysmography (PPG), or chest-straps, which rely on electrocardiography (ECG). Wristwatches are popular due to their comfortable form factor but are known to have lower accuracy than chest straps and have significant lag, which precludes the ability to track rapid changes in heart rate. We are developing Trace, a fully self-contained, earlobe-mounted, wireless PPG CHRM which is 10-fold smaller than previously reported devices. Placement on the earlobe, where there are no muscles or tendons, is less susceptible to noise artifacts. We demonstrate the tracking of heart rate during high intensity interval training (HIIT), where heart rate changes rapidly and sensor lag cannot be tolerated. Notable is Trace’s ability to measure heart rate recovery (HRR), an advanced metric commonly used by athletes to monitor fatigue, and by physicians to assess cardiovascular risk.
Training athletes with accurate heart rate sensors with beat-to-beat accuracy can be used to obtain more precise analytics for athletes, including adaptation and recovery rates. Training athletes with accurate heart rate sensors with beat-to-beat accuracy can be used to obtain more precise analytics for athletes, including adaptation and recovery rates. These analytics go beyond simple heart rate to give athletes a more accurate picture of fitness level and training fatigue.
This project is sponsored by the Michigan Translational Research and Commercialization Fund (MTRAC), developed and managed by the Michigan Economic Development Corporation (MEDC). MTRAC helps advance university discoveries and research to the commercial market.
A. Fatima
We are developing a novel, label-free, inline chemical detector based on the surfactant retardation effect, first discovered in the 1960s. By amplifying this effect in microfluidic channels, we can use it to detect proteins and surface-active molecules at ng/mL concentration.
Inline chemical detectors, commonly used in analytical chemistry, quantify analytes based on a variety of chemical properties, but to date, none can do so based on adsorption or solubility properties. This paper presents a novel inline chemical sensing modality, where analyte adsorption changes the frequency of droplets generated in a microfluidic junction. Proteins and other surface-active agents adsorb to the droplet interface and resist droplet flow by the surfactant retardation effect, thereby reducing the drop frequency. SHRED leverages the amplification of this effect in microfluidic channels. The method is repeatable and can perform linear quantitation of hydrophobic proteins and other surface active analytes with a detection limit of as little as 200 pg.
A. Akram, S. Noman, R. Javid, J. Ram
We are developing systems to detect live organisms in ballast water, for preventing invasive species in the Great Lakes.
Foreign vessels entering the Great Lakes sometimes inadvertently bring invasive species which can impact the fragile freshwater ecosystem which supplies 20% of the world's freshwater. As part of Professor Jeffrey Ram's team (Wayne State School of Medicine), we designed AFIDD (Automated Fluorescence Intensity Detection Device), a biodetection system which can detect living organisms in ballast tanks. The system is based on a fluorescein diacetate (FDA) assay developed by Prof. Ram. The Microfluidics and Bioinstrumentation lab helped develop an automated system which captures organisms on a reusable filter, and monitors real-time fluorescence with teh number of organisms. The system has been piloted in Michigan and Maryland.
This project is sponsored by the Great Lakes Protection Fund.
A. Vedhanayagam
Droplet Morphometry and Velocimetry (DMV) is a video processing software for tracking the droplet size, velocity, trajectory, and other parameters. It is available for free for academic researchers, and is used worldwide.
When performing biochemical assays in droplets, a great deal of relevant information is encoded into a droplet's physical characteristics, such its size, shape, velocity, trajectory, and pixel intensity. Indeed, many recent reports utilize such characteristics as quantitative measurements for label-free assays. The challenge for researchers in droplet microfluidics is that much of the analysis must be done manually. DMV is a machine vision software which uses image processing techniques to identify and track droplets in digital videos, providing quantitative, time-resolved, label-free measurements. DMV tracks 20 different parameters, including size, shape, trajectory, velocity, pixel statistics, and nearest neighbor spacing. Our Lab on a Chip paper provides details on DMV and how it can be used to analyze common droplet operations and systems reported by industry and academic labs, including: droplet generators, splitting and merging devices, cell encapsulation, serial dilutions, emulsion packing, size distributions and sorting efficiency. DMV provides throughputs of 2-30 frames per second.
DMV is available free of charge to academic researchers. It is currently in use by 35 labs in 14 countries worldwide for droplet and particle tracking as well other as other applications such as insect flight analysis. To obtain a download link, please fill out the DMV request form, and email Prof. Amar Basu at abasu AT eng DOT wayne DOT edu. Accompanying the software are a video training tutorial, installation tutorial and a playlist of videos showing the application of DMV in various operations. We welcome your feedback and novel applications of DMV.
G.K. Kurup
Tensiophoresis is the chemomechanical force on a droplet, which can be used to sort droplets by size and chemical composition.
Supported by the NSF Particulate and Multiphase Processes Program under award #CBET-1236764
Sorting droplets based on size and chemical contents is an important capability in droplet-based high throughput screening. We are investigating a novel, label-free sorting technique called tensiophoresis. Tensiophoresis exploits liquid-liquid capillary migration of droplets in a controlled interfacial tension (IFT) gradient in a manner analogous to other phoretic separation techniques. We can generate a sharp IFT gradient by using two laminar streams with differing surfactant concentration. The IFT in the two streams can differ by >10 mN/m, yielding substantial capillary pressures. As a result, droplets near the interface migrate down the IFT gradient toward the upper stream. The migration velocity is dependent on the droplet's size and IFT, enabling sorting based on both of these parameters.
The ability to sort droplets by their IFT is particularly interesting, because it is closely linked to the droplet's chemical composition. Droplets containing pure water (left) migrate to the lower bifurcation, while those containing sodium dodecyl sulfate (right) do not. This is the first known label free approach for sorting droplet microreactors based on their biochemical contents.
G.K. Kurup, A. Doshi
Optofluidic tweezers utilizes balanced thermocapillary flows to trap and manipulate droplets using a focused laser beam. OFT have forces more than 100,000 times greater than traditional optical tweezers.
Supported by the NSF Electronic, Photonic, and Magnetic Devices Program under award #ECCS-1232226
Optical techniques for manipulating liquids and particles have been a long standing interest in physics and biology. Optical tools are attractive because they provide dynamic manipulation and do not require on-chip structures. Optical tweezers (OT) have been widely used, but are not ideally suited for large scale manipulation because they have relatively low force (pN), and the forces are typically repulsive. Optoelectronic tweezers (OET) can provide larger forces (nN), but they require on-chip electric fields. We are investigating optofluidic tweezers (OFT), where droplets are trapped and manipulated using optically generated, spherically confined thermocapillary flows. This approach can trap droplets with holding forces in the µN range, which are 100 stronger than OET, and >100,000 times stronger than optical tweezers.
S. Hamed, P. Sehgal, M. Utomo
Droplet fractionation encapsulates chemically separated compounds into droplets, enabling nL-pL fractions to be collected without physical containers.
Supported by the NSF Chemical and Biological Separations Program under award #CBET-1032603
Biochemical samples are complex mixtures containing 1000’s of components which often must be fractionated prior to analysis. Conventional fraction collectors, which can only accommodate 10’s of fractions, are not well suited for high throughput analysis. In droplet microfluidics, one of the challenges is how to create a library of droplets containing different chemical compounds. Microfractionation in droplets (µFD) is a scalable microfluidic technique for fractionating complex mixtures into droplet containers. A drop generator, placed downstream from a high performance liquid chromatography (HPLC) column, encapsulates the separated components into a serial array of monodisperse droplets. This prevents dispersion of the separated compounds, and allows thousands of droplet fractions without phsyical containers. The droplet library can be stored and subsequently mixed with a target reagent using a downstream tee junction. In principle, µFD can be coupled to a wide variety of separation processes, enabling high throughput fractionation and screening of complex mixtures in µL to sub-nL volumes.
G.K. Kurup
This project concentrates particles within droplets by exploiting microvortex flow within the droplet.
V. Trivedi, A. Doshi, P. Sehgal
We demonstrate that droplet generation, merging, and analysis can be carried out in commercial laboratory tubing.
T. Mertiri, M. Chen
We developed 96-well plates with the ability to control light intensity in each well. These have been used for screening photosynthetic algae and more recently for optogenetic screening.
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BioMEMS and BioInstrumentation is an interdisciplinary graduate level course is open to students in engineering, chemistry, physics, and life sciences. It will cover the fundamentals of biomedical micro and nanosystems, with a focus on lab-on-a-chip technologies. Students will learn about the miniaturization of analytical systems used in biology, chemistry, and medicine. Topics of interest to engineering and physics students include: micro and nanofabrication techniques, the physics of microfluidic flow and other microscale phenomena, and computational modeling techniques. Students in life science and chemistry will learn emerging analytical techniques, molecular/particle/cell separations on chip, single cell assays, and detection methods.
Lecture Recordings
ECE 4570 is a senior level undergraduate course covering aspects of electrical properties of semiconductors, the physical electronics of P-N junction, bipolar, field effect transistors, and device fabrication technology essential to understanding semiconductor active devices and integrated circuits. Introduction to the behavior of semiconductor and electronics devices. Students also take part in a semiconductor fabrication lab, where they learn about the microfabrication processes used to manufacture and test semiconductor devices including resistors, diodes, and MOSFETs.
Nanotechology is quickly becoming a pervasive and fundamental component of science and technology. The microfluidics laboratory is collaborating with the Detroit Science Center, the city's premiere source for K-12 science education, to develop modules for educating and inspiring future scientists and engineers in the micro and nanoscale worlds.
Sponsored by the National Science Foundation's Michigan Louis Stoke Alliance Minority Participation (MI-LSAMP) program, SURA is an effort designed by Wayne State's MI-LSAMP Work Group to provide summer research opportunities primarily to first and second year undergraduate students at Wayne State and other partner institutions, including Michigan State University, University of Michigan-Ann Arbor, and Western Michigan University. MI-LSAMP aims to significantly increase the number of minority students earning baccalaureate degrees each year in Science, Technology, Engineering and Mathematical (STEM) fields and prepare them for entry into graduate programs.
