(7aq) Electrokinetic Analytical Tools for Cell Characterization and Biosensing Technology

Stem cells have great therapeutic potential because of their differentiation capacity and protective properties. Sufficiently characterizing stem cells functional behavior before use in transplant therapy is essential to the development of reliable therapeutics. Dielectrophoresis (DEP), an advancing electrokinetic technique, is used to examine cell populations and quantify their biophysical properties. One such property, membrane capacitance is an emerging biomarker that provides insight to cellular function. My research interests include using DEP technology for biosensing and stem cell characterization/processing for disease monitoring and eventual treatment.

Postdoctoral Research:

I am a postdoctoral research fellow in the Neurology Department at the University of California Irvine (UCI). I work under the direction of Dr. Lisa Flanagan and use DEP to study neural stem and progenitor cells (NSPCs). I’ve examined NSPCs dielectric properties from multiple sources (brain-derived, mouse-derived, and embryonic-derived) and their links to differentiation. I’ve quantified NSPCs membrane capacitance and harnessed this information to sort mouse-derived NSPCs as well as brain-derived NSPCs in batch and continuous systems. This is critical because NSPCs can be expanded in cell culture for post-separation processing to test in stroke and spinal cord injury models. I’m currently involved in a mouse spinal cord injury model. Embryonic-derived NSPCs were transplanted after a spinal cord injury was induced and behavioral data was collected. My specific contributions include DEP characterization of transplanted cells along with behavioral data analysis.

Postdoctoral Awards:

(1) National Science Foundation Postdoctoral Research Fellowship in Biology 2016

(2) UCI Chancellor’s ADVANCE Postdoctoral Fellowship 2016

(3) Society of Women Engineers ASSIST Travel Grant 2016

(4) AES/BioMicrofluidics Art in Science Competition, 1^st place Video 2016

PhD Research:

Prior to UCI I completed my M.S. and Ph.D. in Chemical Engineering at Michigan Technological University. Under the supervision of Dr. Adrienne Minerick, my PhD research focused on DEP-based cell separations for stem cell therapeutics. Specifically, I studied the polarization mechanisms of small particles such as polystyrene beads, human mesenchymal stem cells (hMSCs), and red blood cells to determine their unique dielectric properties. For hMSCs, I developed a morphology standardization procedure to accurately characterize their dielectric behavior. My major accomplishment was the quantification of hMSCs membrane capacitance and permittivity detailed in a peer-reviewed publication. Membrane capacitance may be used as a unique biomarker for hMSC subpopulations, which is essential to sorting hMSCs as a potential therapy for type 1 diabetes. Another aspect of my research was the development of a new DEP data collection and analysis technique for blood typing. I examined the use of frequency sweep rates to accurately quantify particles DEP response. I optimized the frequency sweep rate allowing a continuous DEP spectra to be obtained (nontraditional method) for polystyrene beads and red blood cells. This provides DEP researchers a fast data collection and analysis procedure, which is essential to achieve rapid blood typing (and cell separations). This frequency sweep technique has a patent No. WO2015051372-A1, April 2015.

Select PhD Awards:

(1) Doctoral Finishing Fellowship, Michigan Technological University 2013

(2) Anderson Research Scholarship, Michigan Technological University 2012

(3) Biotech Research Center Merit Award, Michigan Technological University 2012

(4) Graduate School Dean’s Fellowship, Michigan Technological University 2011-2012

(5) King-Chavez-Parks Future Faculty Fellowship, Michigan Technological University 2009-2013

(6) National GEM Consortium Fellowship 2009-2010 (funded M.S. research)

Future Research Direction:

Just as cell phones have become essential and are prominent in society, portable biosensors are headed in the same direction. Chronic diseases such as heart disease, diabetes, stroke and obesity are the leading causes in preventable death and disability in the U.S. claiming more than 950,000 lives each year. It is projected that healthcare in the U.S. will reach 30% of the GDP by 2040. This necessitates the need for portable biosensors for cell characterization and processing to facilitate early disease detection, and wearable biosensors for patient monitoring as a form of preventative healthcare. My research explorations will be conducted at the cellular, organ, and exercise science levels.

Cell Characterization and Sorting: Stem cells therapeutic potential is difficult to achieve because their cultures are heterogeneous containing stem cells, partially differentiated progenitor cells, and fully differentiated cells. For example, neural stem cells contain astrocyte, neuron and oligodendrocyte progenitors, and mesenchymal stem cells contain adipocyte, myocyte, and chondrocyte progenitors. Little is known about the defining characteristics of these progenitor cells and which are best for healing. DEP uses electric fields to induce cell motion, and can be used to sort progenitor cells based on their intrinsic properties (membrane capacitance) allowing for downstream cellular analysis. DEP and other electrokinetic techniques will be implemented to develop membrane capacitance as a reliable progenitor cell biomarker. Effectively characterizing and sorting stem cells is essential to further study these cells as treatment options for chronic diseases.

Microfluidic Biosensor for Disease Monitoring: Doctors screen for stroke and heart disease risks through blood tests. DEP has been used to discriminate between healthy and diseased red blood cells (RBCs), this foundation will be used to characterize differences in healthy and unhealthy RBCs as they relate to kidney and liver function. Creatinine and albumin, protein biomarkers, are used as indicators of kidney and liver function, respectively. Creatinine is linked to the glomerular filtration rate (GFR) with high creatinine concentrations indicating low GFR. Low albumin concentrations imply diminished liver capacity, and the body is not absorbing enough essential nutrients. Creatinine and albumin are good biomarker candidates because they are used in the comprehensive metabolic panel. The goal is to develop a single microfluidic platform to quickly assess creatinine and albumin concentrations in small volumes of blood.

Exercise-related Biomarker Detection: There are chemical biomarkers related to exercise that are detectable in electrokinetic-based microfluidic devices. Consider dehydration, a person has loss high concentrations of salt affecting their muscles ability to retain water causing cramps. Salt concentrations are detectable in sweat along with other minerals, urea, and lactate. A wearable multiwell microfluidic device will be used to collect and analyze sweat for mineral content to provide health status information. Ultimately the goal is to build a profile of mineral losses during exercise to maximize recovery. This is especially important for people using exercise as an early chronic disease treatment option.

Electrokinetic techniques are promising analytical tools for stem cell characterization and sorting, chronic disease monitoring, and exercise assessments.

Teaching Interests:

My teaching interests reside within my teaching philosophy, every student needs a champion! Being a champion for students means supporting them in the classroom. My strategy is to create a comfortable, nonthreatening classroom environment where questions and feedback are encouraged. Beyond striving to ensure students learn fundamental course content my objectives are to: (a) foster critical thinking and problem solving skills; (b) develop life-long learning skills; and (c) prepare social and globally conscious engineers. As a professor, I want to inspire students and help them reach their scholarly potential.

During my Ph.D. program, I had the opportunity to gain experience as a teaching assistant (TA). I TA’d Fundamentals of Chemical Engineering II, a class with 52 students, which covered mass and energy balances, flow and piping systems, pumps, compressors, and stage-wise separations. I also TA’d Thermodynamics for Chemical Engineers a class with 60 students that covered the first and second law of thermodynamics applied to open and closed systems, energy conversions, power cycles, and entropy/enthalpy calculations. Serving as a TA was valuable because I learned how to provide students with additional classroom support and how to structure office hours. Now, I teach two chemistry labs at a local community college.

With my experience, I am prepared to teach core chemical engineering undergraduate and graduate courses. Additionally, I would like to develop content and teach courses related to Medical Microdevices, Stem Cell Engineering, and Bioengineering.

Publications

(1) Adams, T.N.G., Ro, C.R., Tiwari, S., Anderson, A.J., Cummings, B.J., and Flanagan, L.A., Characterizing human stem cell function with dielectrophoresis and flow cytometry (in preparation).

(2) Adams, T.N.G., Flanagan, L.A., and Minerick, A.R., Membrane capacitance as a live cell marker for human mesenchymal stem cell therapeutics: a review on advances in dielectrophoresis technology (in preparation).

(3) Adams, T.N.G., Jiang, A.Y.L., Vyas, P.D., Flanagan, L.A., Separation of neural stem cells by whole cell membrane capacitance, METHODS: Neural Stem Cells in Health and Disease (in review).

(4) Adams, T.N.G., Turner, P., Zhao, F., Janorkar, A., and Minerick, A.R., Characterizing the Dielectric Properties of Human Mesenchymal Stem Cells and the Effects of Charged Elastin-like Polypeptide Copolymer Treatment, Biomicrofluidics, 8, 054109, 2014.

(5) Adams, T.N.G., Leonard, K.M., and Minerick, A.R., Frequency Sweep Rate Dependence on the Dielectrophoretic Response of Polystyrene Beads and Red Blood Cells, Biomicrofluidics, 7, 064114, 2013.

(6) Adams, T., Yang, C., Gress, J., Wimmer, N., and Minerick, A.R., A Tunable Microfluidic Device for Drug Delivery, Advances in Microfluidics, InTech Open Science, 2012.

(7) Adams, T.N.G., Olson, T., King, J., and Keith, J., In-Plane Thermal Conductivity Modeling of Carbon Filled Liquid Crystal Polymer Based Resins, Journal of Polymer Composites, 32, 147-157, 2011.