Research

What is electrophysiology?

Electrophysiology is a field of physiology that studies the electrical properties of biological cells and tissues. It involves measurements of voltage changes or electric current or manipulations on a wide variety of scales from single ion channel proteins to whole organs like the heart. Nernst, Goldman and Hodgkin and Katz showed that the ionic imbalance between intracellular and extracellular spaces creates an electrochemical potential (termed the membrane potential Vm.

What is the utility of electrophysiology?

Electrophysiology can characterize many cellular functions and can discriminate subtle differences between cells. Dielectrophoresis (DEP) is one electrokinetic phenomena that involves the interactions between a non-uniform electric field and a polarizable interface, like a cell's membrane in a media, or the cytoplasm and the inner membrane leaflet. DEP analysis provides measurement of three key properties: membrane conductance (GEFF), membrane capacitance (CEFF), and cytoplasm conductivity (σcyt). Electrophysiology can characterize many cellular functions and can discriminate subtle differences between cells. DEP methods have discriminated subtle differences between cells that has been demonstrated in cancer phenotyping, apoptosis progression, stem cell differentiation, and drug screening.

Current Research

Electrophysiology of Red Blood Cells

Electrophysiological studies of RBCs have revealed dynamic changes in RBC ion channels (Thoams, 2011; Minetti, 2013; Rototdam, 2019) and have provided important insights into disease progression including in malaria, diabetes, and anemias (Tokumasu, 2012; Jeon, 2017; Gaikwad, 2018; Kaestner, 2020). Even when no disease is present, such as in blood transportation and storage as well as circadian rhythms, electrophysiology has proven useful (Silva, 2012; Makhro, 2016; Silva, 2012 Henslee, 2017; Beale, 2019; Lavi, 2021). We have shown that electrokinetic properties, Dielectrophoresis (DEP) and surface zeta-potential can provide label-free, rapid, low cost, and high-resolution RBC monitoring in isolated RBCs as well as whole blood in many applications including circadian timing, drug screening, and disease monitoring. One of our research focuses is developing clinically relevant applications of this work.

Oxidative Stress and RBC Eryptosis

There are critical gaps in the study of oxidative stress (OS) and eryptosis in red blood cells (RBCs). In this study we intend to validate a Dielectrophoresis (DEP)-based approach in the analysis of RBCs. This will reveal changes to RBC electrophysiology, in three key electrophysical properties, membrane conductance, membrane capacitance, and cytoplasm conductivity. Oxidative stress (OS) in RBCs is important as it irreversibly damages the cells, impairs oxygen delivery, and induces red blood cell aging and hemolysis. We intend to develop a method of detection for eryptosis based on our OS study. Further, OS is found to be a dominant factor in RBC-related and other diseases such as malaria and sickle-cell disease. DEP has been proven to give repeatable and consistent results when measuring healthy RBC samples and analysis of OS affected cells could lead to a for robust marker of oxidative stress. Further validating these results using known methods of OS detection will demonstrate that DEP parameters can sufficiently characterize OS in RBCs providing a rapid and label-free method in the study of OS RBC electrophysiology.

Cell Sorting with CytoRecovery

Using the 3DEP system we are able to determine distinct electric field conditions to apply in commercially available Cytorecovery system that uses high voltages contactless dielectrophoresis to seperate and sort cells. Our research will focus on seperating healthy and damaged cells due to a myriad of drug treatments and conditions to induce oxidative stress in blood cells.

ECMO Blood Clotting

One of our research projects investigates electrical variations in whole blood samples cycled through extracorporeal membrane oxygenation (ECMO) circulatory support systems to predict blood clotting and ECMO failure will be presented.

Electrophysiology of Cancer Cells

Investigation of Platinum-Acridine Cancer Drug Cellular Uptake and Mechanism of Cell Death using 3DEP Platform

This novel research assesses the DEP response of cancer cells exposed to P8A1, a highly cytotoxic platinum-acridine (PA) cancer drug. initial experiments elucidate changes in electrophysiology in P8A1 treatment. Our initial dose response results saw an increase in membrane conductance and cytoplasmic conductivity after 3 hours of 100nM treatment, indicating DEP’s ability to functionally monitor drug uptake (0-6 hours post treatment) prior to cell death that occurs after 6 hours of drug exposure.

Electrophysiology of Cancer Cells

Electrical Properties Changed of Jurkat Cell Membrane Due to Oxidative Stress and Eryptosis

There are critical gaps in the study of oxidative stress (OS) and eryptosis in red blood cells (RBCs). In this study we intend to validate a Dielectrophoresis (DEP)-based approach in the analysis of RBCs. This will reveal changes to RBC electrophysiology, in three key electrophysical properties, membrane conductance, membrane capacitance, and cytoplasm conductivity. Oxidative stress (OS) in RBCs is important as it irreversibly damages the cells, impairs oxygen delivery, and induces red blood cell aging and hemolysis. We intend to develop a method of detection for eryptosis based on our OS study. Further, OS is found to be a dominant factor in RBC-related and other diseases such as malaria and sickle-cell disease. DEP has been proven to give repeatable and consistent results when measuring healthy RBC samples and analysis of OS affected cells could lead to a for robust marker of oxidative stress. Further validating these results using known methods of OS detection will demonstrate that DEP parameters can sufficiently characterize OS in RBCs providing a rapid and label-free method in the study of OS RBC electrophysiology.