Alternating Current Electrohydrodynamics Induced Nanoshearing and Fluid Micromixing for Specific Capture of Cancer Cells (original) (raw)
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Analytical Chemistry, 2014
We report a tunable alternating current electrohydrodynamic (ac-EHD) force which drives lateral fluid motion within a few nanometers of an electrode surface. Because the magnitude of this fluid shear force can be tuned externally (e.g., via the application of an ac electric field), it provides a new capability to physically displace weakly (nonspecifically) bound cellular analytes. To demonstrate the utility of the tunable nanoshearing phenomenon, we present data on purpose-built microfluidic devices that employ ac-EHD force to remove nonspecific adsorption of molecular and cellular species. Here, we show that an ac-EHD device containing asymmetric planar and microtip electrode pairs resulted in a 4-fold reduction in nonspecific adsorption of blood cells and also captured breast cancer cells in blood, with high efficiency (approximately 87%) and specificity. We therefore feel that this new capability of externally tuning and manipulating fluid flow could have wide applications as an innovative approach to enhance the specific capture of rare cells such as cancer cells in blood.
2014
We report a multiplexed microfluidic device for highly specific capture and detection of multiple exosome targets using a tuneable alternating current electrohydrodynamics (ac-EHD) forces-referred to as nanoshearing [1,2]. These forces generated within few nanometers of an electrode surface (i.e., double layer) to generate nanoscaled fluid flow that enhances the specificity of capture and also remove the nonspecifically adsorbed species from the electrode surface. To demonstrate the utility of this phenomenon, we present data on purpose-built microfluidic devices that employ ac-EHD induced surface shear forces to specifically capture exosomes isolated from complex biological fluids (e.g., cell culture media, serum etc.) [3].
Analytical Chemistry, 2014
Exosomes show promise as non-invasive biomarkers for cancers, but their effective capture and specific detection is a significant challenge. Herein, we report a multiplexed microfluidic device for highly specific capture and detection of multiple exosome targets using a tunable alternating current electrohydrodynamic (ac-EHD) methodology-referred to as nanoshearing. In our system, electrical body forces generated by ac-EHD act within nanometers of an electrode surface (i.e., within the electrical layer) to generate nanoscaled fluid flow which enhances the specificity of capture and also reduce nonspecific adsorption of weakly bound molecules from the electrode surface. This approach demonstrates the analysis of exosomes derived from cells expressing human epidermal growth factor receptor 2 (HER2) and prostate specific antigen (PSA), and also capable of specifically isolating exosomes from breast cancer patient samples. The device also exhibited a 3-fold enhancement in detection sensitivity in comparison to hydrodynamic flow based assays (LOD 2750 exosomes/µL for ac-EHD vs LOD 8300 exosomes/µL for hydrodynamic flow; (n = 3)). We believe this approach can potentially find its relevance as a simple and rapid quantification tool to analyze exosome targets in biological applications.
Microfluidic Device for Electric Field-Driven Single-Cell Capture and Activation
Analytical Chemistry, 2005
A microchip that performs directed capture and chemical activation of surface-modified single cells has been developed. The cell capture system is comprised of interdigitated gold electrodes microfabricated on a glass substrate within PDMS channels. The cell surface is labeled with thiol functional groups using endogenous RGD receptors, and adhesion to exposed gold pads on the electrodes is directed by applying a driving electric potential. Multiple cell types can thus be sequentially and selectively captured on desired electrodes. Single-cell capture efficiency is optimized by varying the duration of field application. Maximum single-cell capture is attained for the 10-min trial, with 63 (9% (n) 30) of the electrode pad rows having a single cell. In activation studies, single M1WT3 CHO cells loaded with the calciumsensitive dye fluo-4 AM were captured; exposure to the muscarinic agonist carbachol increased the fluorescence to 220 (74% (n) 79) of the original intensity. These results demonstrate the ability to direct the adhesion of selected living single cells on electrodes in a microfluidic device and to analyze their response to chemical stimuli.
Manipulating particles in microfluidics by floating electrodes
ELECTROPHORESIS, 2010
Various particle manipulations including enrichment, movement, trapping, separation, and focusing by floating electrodes attached to the bottom wall of a straight microchannel under an imposed DC electric field have been experimentally demonstrated. In contrast to a dielectric microchannel possessing a nearly uniform surface charge (or z potential), the metal strip (floating electrode) is polarized under the imposed electric field, resulting in a nonuniform distribution of the induced surface charge with a zero net surface charge along the floating electrode's surface, and accordingly induced-charge electroosmotic flow near the metal strip. The induced induced-charge electroosmotic flow can be regulated by controlling the strength of the imposed electric field and affects both the hydrodynamic field and the particle's motion. By using a single floating electrode, charged particles could be locally concentrated in a section of the channel or in an endreservoir and move toward either the anode or the cathode by controlling the strength of the imposed electric field. By using double floating electrodes, negatively charged particles could be concentrated between the floating electrodes, subsequently squeezed to a stream flowing in the center region of the microchannel toward the cathodic reservoir, which can be used to focus particles.
Scientific Reports, 2015
Microfluidic channels have been implemented to detect cancer cells from blood using electrical measurement of each single cell from the sample. Every cell provided characteristic current profile based on its mechano-physical properties. Cancer cells not only showed higher translocation time and peak amplitude compared to blood cells, their pulse shape was also distinctively different. Prevalent microfluidic channels are plain but we created nanotexture on the channel walls using micro reactive ion etching (micro-RIE). The translocation behaviors of the metastatic renal cancer cells through plain and nanotextured PDMS microchannels showed clear differences. Nanotexture enhanced the cell-surface interactions and more than 50% tumor cells exhibited slower translocation through nanotextured channels compared to plain devices. On the other hand, most of the blood cells had very similar characteristics in both channels. Only 7.63% blood cells had slower translocation in nanotextured micro...
2014
We describe a new multiplexed device for the sensitive detection of multiple protein biomarkers in serum by using an alternating current (ac) electrohydrodynamics (ac-EHD) induced surface shear forces based phenomenon referred to as nanoshearing [1,2]. The tunable nature (via manipulation of ac field) of nanoshearing forces can enhance the capture performance of the devices (i.e., enhances the number of sensor-target collisions). This can also selectively displace nonspecifically bound molecules from the electrode surface (i.e., shear forces can be tuned to shear away nonspecific species from biological fluids). To demonstrate the utility and applicability of this phenomenon, we present data on a purpose-built microfluidic device that employs nanoshearing to specifically capture protein biomarkers from complex biological fluids [3].