Microfluidic electromanipulation with capacitive detection for the mechanical analysis of cells

Abstract

The mechanical behavior of cells offers insight into many aspects of their properties. We propose an approach to the mechanical analysis of cells that uses a combination of electromanipulation for stimulus and capacitance for sensing. To demonstrate this approach, polystyrene spheres and yeast cells flowing in a 25 m ϫ 100 m microfluidic channel were detected by a perpendicular pair of gold thin film electrodes in the channel, spaced 25 m apart. The presence of cells was detected by capacitance changes between the gold electrodes. The capacitance sensor was a resonant coaxial radio frequency cavity ͑2.3 GHz͒ coupled to the electrodes. The presence of yeast cells ͑Saccharomyces cerevisiae͒ and polystyrene spheres resulted in capacitance changes of approximately 10 and 100 attoFarad ͑aF͒, respectively, with an achieved capacitance resolution of less than 2 aF in a 30 Hz bandwidth. The resolution is better than previously reported in the literature, and the capacitance changes are in agreement with values estimated by finite element simulations. Yeast cells were trapped using dielectrophoretic forces by applying a 3 V signal at 1 MHz between the electrodes. After trapping, the cells were displaced using amplitude and frequency modulated voltages to produce modulated dielectrophoretic forces. Repetitive displacement and relaxation of these cells was observed using both capacitance and video microscopy.

Microwave frequency sensor for detection of biological cells in microfluidic channels

“…The effective permittivity for a yeast cell, for example, is determined using a double-shell structure model. 20,26 The signals resulting from particles flowing at different distances above the electrodes will look similar to profiles shown in Fig. 5.…”

“…[12][13][14][15][16][17][18] These undesirable outcomes can be eliminated or greatly reduced if the sensing is performed at higher gigahertz frequencies, where capacitance sensitivity tends to increase. 19 Detection systems based on flow impedance measurements 20,21 have several advantages over the more traditional optical methods. 22,23 They are highly sensitive, easy to set up and control, and allow high throughput screening and analysis of cellular properties and function using sample volumes on the order of microliters.…”

“…3, a cell passing over the electrodes is included by a capacitance ⌬C cell ; cell capacitance can be modeled using Eq. ͑5͒ and numerical simulations of the field between the electrodes, 20 which depend on the cell position in the channel. The circuit is simulated using ANSOFT DESIGNER microwave circuit simulator, with model parameter values initially obtained from physical dimensions and use of first order physical models.…”

Dielectric Characterization of the Yeast Cell Budding Cycle

“…These values were carefully selected among the experimental data available in the literature. In particular, the thicknesses of the thick and thin cell walls and the radius of the cytoplasm were taken from published data of scanning (SEM) and transmission (TEM) electron micrographs [43][44][45][46][47], and the value for the very low conductivity of the membrane was fixed to be 10 −7 S/m [48]. In addition, we have assumed that the suspending medium does not exhibit a dielectric dispersion so that Re(ε rext ) = 80 remains fixed, but we perform the study for different conductivity values σ ext .…”

Dielectrophoresis for Manipulation of Bioparticles

“…The advancements in micro/nano fabrication techniques help in the development of such micro/nano electrode structures to generate the nonuniform electric field in DEP channels (Hughes, 2003). DEP assisted by such miniaturized electrodes have been used for separating, sorting, positioning, trapping, concentrating, and mixing ) of biomolecules such as cells, bacteria, virus, DNA and proteins (Basuray & Chang, 2010;Bunthawin et al, 2010;Church et al, 2009;Du et al, 2008;Ferrier et al, 2008;Gagnon et al, 2009;Hughes, 2003;Hwang et al, 2009;Jones, 1995;Lewpiriyawong et al, 2008;Lin & Yeow, 2007;Nguyen & Werely, 2006;Parikesit et al, 2008;Pohl, 1978;Wei et al, 2009;Yang et al, 2010;Zhu et al, 2010). These applications of DEP for manipulating such bioparticles has been further exploited in different fields namely drug delivery, food diagnostics, point of care analysis, biomedical, etc (Hughes, 2003).…”