Cancer, pre-cancer and normal oral cells distinguished by dielectrophoresis

Abstract

Most oral cancers are oral squamous cell carcinomas (OSCC) that arise from the epithelial lining of the oral mucosa. Given that the oral cavity is easily accessible, the disease lends itself to early detection; however most oral cancers are diagnosed at a late stage and approximately half of oral cancer sufferers do not survive beyond 5 years, post-diagnosis.The low survival rate has been attributed to late detection but there is no accepted, reliable and convenient method for the detection of oral cancer and oral pre-cancer.Dielectrophoresis (DEP) is a label-free technique which can be used to obtain multiparametric measurements of cell electrical properties. Parameters, such as cytoplasmic conductivity and effective membrane capacitance (CEff), can be non-invasively determined by the technique. In this study, a novel lab-on-a-chip device was used to determine the cytoplasmic conductivity and CEff of primary normal oral keratinocytes, and pre-cancerous and cancerous oral keratinocyte cell lines.Our results show that the electrical properties of normal, pre-cancerous and cancerous oral keratinocytes are distinct. Furthermore, increasing CEff and decreasing cytoplasmic conductivity correlate with disease progression which could prove significant for diagnostic and prognostic applications. DEP has the potential to be used in a primary health care setting as a non-invasive and non-subjective technique to detect oral cancer and oral precancer.3

Characterization of a hybrid dielectrophoresis and immunocapture microfluidic system for cancer cell capture

“…This trend suggests that the DEP response of the cells was stronger at higher frequencies, as confirmed in the proportionate DEP response data shown in Figure 3 The curve fits for ℜ(f̃C M ) in Figure 3(b) were calculated by modeling the LNCaP cell as a single-shelled dielectric sphere with a frequency-dependent DEP response primarily dictated by a specific membrane capacitance, C membrane [52]. In the high-conductivity cases, the pDEP response and crossover frequency regions were fit well; the magnitude and frequency dependence, as well as the fit value for C membrane , were similar to those previously reported for other cancer cells [54][55][56]. Yang et al reported on DEP separation of LNCaPs from colorectal cancer cells, but used a higher conductivity media (σ m = 300 mS/m) at which LNCaPs experienced nDEP even in the MHz range [44].…”

Automated electrorotation shows electrokinetic separation of pancreatic cancer cells is robust to acquired chemotherapy resistance, serum starvation, and EMT

“…According to Wang et al, 41 Shim et al, 8 and Gascoyne et al, 42 this increase in surface area would putatively change the ruffles and folds in the cell membrane, increasing their effective surface area and specific membrane capacitance. Furthermore, Salmanzadeh et al 49 and Mulhall et al 50 observed that aggressiveness of cancer cell phenotype correlates with an increase in specific membrane capacitance for mouse ovarian surface epithelial and oral cancer cells, respectively. We, however, observed no significant change in the electrical properties of EMT-induced PANC1 cells.…”

“…These differences could have arisen from many possible factors including different cell lineages, different growth conditions, dysregulation of ion concentration due to altered cell metabolism or cell signaling, differences in ion permeability of interior cell structures, or differences in the concentration of non-ionic species. Mulhall et al distinguishes between non-cancerous and cancerous oral cells based on their cytoplasmic conductivity, 50 noting that decreased cytoplasmic conductivity is associated with progression.…”

Human oral cancer cells with increasing tumorigenic abilities exhibit higher effective membrane capacitance

“…Dielectric methods have also been used to separate breast cancer cells from blood 19 , and to distinguish stem cells from their progeny 20 . Recently, DEP has been used to study the electrical effects of sphingosine on mouse ovarian cancer progression models 21 and discriminate normal oral cells from pre-cancerous and neoplastic oral cell lines 22 . DEP offers many advantages over other methods of measuring cell electrophysiology; it requires no markers and is not confounded by cell-marker interactions (unlike flow cytometry 17 ), and can examine many cells (typically 1000+) simultaneously, unlike patch clamp (where costly high-throughput systems have much lower throughput).…”