Dielectrophoretic analysis of treated cancer cells for rapid assessment of treatment efficacy

Abstract

Whilst personalized medicine (where interventions are precisely tailored to a patient's genotype and phenotype, as well as the nature and state of the disease) is regarded as an optimal form of treatment, the time and cost associated with it means it remains inaccessible to the greater public. A simpler alternative, stratified medicine, identifies groups of patients who are likely to respond to a given treatment. This allows appropriate treatments to be selected at the start of therapy, avoiding the common "trial and error" approach of replacing a therapy only once it is demonstrated to be ineffective in the patient. For stratification to be effective, tests are required that rapidly predict treatment effectiveness. Most tests use genetic analysis to identify drug targets, but these can be expensive and may not detect changes in the phenotype that affect drug sensitivity. An alternative method is to assess the whole-cell phenotype by evaluating drug response using cells from a biopsy. We assessed dielectrophoresis to assess drug efficacy on short timescales and at low cost. To explore the principle of assessing drug efficacy we examined two cell lines (one expressing EGFR, one not) with the drug Iressa. We then further explored the sensitive cells using combinations of chemotherapeutic and radiotherapeutic therapies. Our results compare with known effects of these cell/treatment combination, and offer the additional benefit over methods such as TUNEL of detecting drug effects such as cell cycle arrest, which do not cause cell death.

Quantitative Model for Ion Transport and Cytoplasm Conductivity of Chinese Hamster Ovary Cells

“…There has been studies showing that cytoplasm conductivity plays an important role in different biological processes such as apoptosis 4–6 , progression of cancer 7–9 , differentiation of stem cells 10 , separation of healthy and tumor cells 11 . One aim of this work is to provide a link between physiological changes and cytoplasm conductivity of CHO cells.…”

“…Changes in ionic content of cells can be an indication of impaired cellular functions and is possible to be detected by measuring the cells cytoplasm conductivity 2,3 . There has been studies showing that cytoplasm conductivity is affected by various processes such as apoptosis 4–6 , progression of cancer 7–9 , differentiation of stem cells 10 , separation of healthy and tumor cells 11 , and drug treatments 9 . Table 1 shows changes in cytoplasm conductivity of various cell lines, as their physiological state changes.…”

Transcriptome-based screening of ion channels and transporters in a migratory chondroprogenitor cell line isolated from late-stage osteoarthritic cartilage

“…in the bone marrow (Ismail, Hughes, Mulhall, Oreffo, & Labeed, 2015). DEP can be used for both assessing the passive electrical properties of cellular components, and as the basis for a separation method (Mahabadi, Labeed, & Hughes, 2018). This could be especially relevant for CPCs present at very low abundance in arthritic cartilage, given that a truly reliable cell surface marker has still not been identi ed.…”

Review: Dielectrophoresis in cell characterization

“…A similar approach extrapolated the principle of light intensity monitoring to a 3D well‐device verified characterizing viable and nonviable yeast [120]. Early versions of this device went on to characterize E. coli , stem cells, atrial myocardium, and cancer cells [121–124] with key parameters summarized in Supporting information Table S2.…”