Dr Krista Clarke is a post-doctoral researcher at the University of Surrey, and was co-funded by ME Research UK and the ME Association to assess the electrical properties of white blood cells in ME/CFS. Krista's thesis has now been published.
Abstract
Dielectrophoresis Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome SARS-CoV-2 PBMC COVID-19 Chondrocyte Diagnosis
Biological cells possess intrinsic electrophysiological properties which are fundamental to cellular function. Changes in cell electrophysiology can act as a biomarker, for example to indicate transition from healthy to diseased cell states, changes in cell function, or cell differentiation. This thesis presents three studies which used dielectrophoresis (DEPtech 3DEP) and ζ-potential analysis (two fast, label-free, high-throughput, non-invasive, and low-cost tools) to examine the electrophysiological properties of two cell types, peripheral blood mononuclear cells (PBMCs) and chondrocytes, for novel medical applications.
The first study investigated the electrophysiological properties of PBMCs in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS); a debilitating disease of unknown pathophysiology with no reliable, validated, and quantitative diagnostic test. The dielectric and ζ-potential response of PBMCs to 1.5-hour hyperosmotic challenge differentiated ME/CFS donors from healthy controls with 81.80% sensitivity and 85.70% specificity. This shows potential as a quantitative diagnostic biomarker
The second study examined whether the electrophysiological properties of PBMCs could act as a correlate of protection to SARS-CoV-2. Cytoplasmic conductivity in unchallenged PBMCs was significantly reduced in donors who had received three SARS-CoV-2 vaccine doses compared with unmatched COVID-19 naïve donors. Stimulation with the receptor binding domain of the SARS-CoV-2 spike protein resulted in significant differences in normalised values of membrane conductance in third-dose vaccinated donors, from COVID-19 naïve and second-dose donors.
The third study investigated chondrocytes, which are used extensively in cell-based cartilage-repair therapies. Chondrocytes rapidly dedifferentiate and become fibroblastic during monolayer cell culture – decreasing the success of reimplantation surgery. Significant changes in chondrocyte electrophysiological properties were observed over time in culture, laying the foundations for the identification of an electrophysiological biomarker that correlates with chondrocytic phenotype, to improve re-implantation outcome.
These studies demonstrate novel applications of dielectrophoresis and ζ-potential analysis – to quantitatively diagnose ME/CFS, identify changes in PBMCs following COVID-exposure, and changes in chondrocyte electrophysiology during dedifferentiation.
MEA Comment
Well Done Krista! On publication of your Doctoral Thesis by the University of Surrey.
The Thesis describes the research into finding a diagnostic biomarker for ME/CFS that Krista and colleagues have been carrying out at the University of Surrey using blood samples from the ME Biobank.
This research has been jointly funded by the MEA Ramsay Research Fund and ME Research UK.
Dr Charles Shepherd,
Trustee and Hon. Medical Adviser to the ME Association,
Member of the 2018-2021 NICE guideline on ME/CFS committee,
Member of the 2002 Chief Medical Officer's Working Group on ME/CFS
Further Information
- The ME Association: Journal of Translational Medicine: The search for a blood-based biomarker for ME/CFS: from biochemistry to electrophysiology | Feb, 2025
- The ME Association: MEA and MERUK Research: Explaining Electrophysiological Properties of Cells in Health and Disease | August, 2024
- The ME Association: Professor Robert Dorey and colleagues update on investigating the electrical properties of blood from people with ME/CFS | July 2, 2024
- The ME Association and ME Research UK announce funding for a study that aims to create a diagnostic test for ME/CFS | October 30, 2023