Biochip With Multi-Planar Electrodes Geometry for Differentiation of Non-Spherical Bioparticles in a Microchannel

Abstract

A biosensor capable of differentiating cells or other microparticles based on morphology finds significant biomedical applications. Examples may include morphological determination in the cellular division process, differentiation of bacterial cells, and cellular morphological variation in inflammation and cancer etc. Here, we present a novel integrated multi-planar microelectrodes geometry design that can distinguish a non-spherical individual particle flowing along a microchannel based on its electrical signature. We simulated multi-planar electrodes design in COMSOL Multiphysics and have shown that the changes in electrical field intensity corresponding to multiple particle morphologies can be distinguished. Our initial investigation has shown that top-bottom electrodes configuration produces significantly enhanced signal strength for a spherical particle as compared to co-planar configuration. Next, we integrated the co-planar and top-bottom configurations to develop a multi-planar microelectrode design capable of electrical impedance measurement at different spatial planes inside a microchannel by collecting multiple output signatures. We tested our integrated multi-planar electrode design with particles of different elliptical morphologies by gradually changing spherical particle dimensions to the non-spherical. The computed electrical signal ratio of non-spherical to spherical particle shows a very good correlation to predict the particle morphology. The biochip sensitivity is also found be independent of orientation of the particle flowing in the microchannel. Our integrated design will help develop the technology that will allow morphological analysis of various bioparticles in microfluidic channel in the future.

Thin Flexible Lab-on-a-Film for Impedimetric Sensing in Biomedical Applications

“…S1a & b. The sensitivity improvement of the modified approach has been predicted in our previous paper using COMSOL 31 . Here, we do the comparative experimental study between the standard (Design S) and modified electrode (Design M) biochips.…”

“…The geometrical electrode configuration was first optimized in COMSOL Multiphysics software in our previous paper 31 . Notably, electrode geometry, i.e., width, position, and size of the gap between the electrodes, were optimized.…”

“…Theoretically, extending the electrodes in the channel direction would result in a higher current between the electrodes. However, it is not beneficial to significantly increase the electrodes' width since this results in inconveniently long particle transition times resulting in flow of multiple cells at a time within the detection volume 31 . The width of the middle electrodes is from 100 to 150 μm for both the standard (Design S) and modified (Design M) design, this was discovered to be a good balance of signal strength and transition length.…”

“…In new layouts, the distance between electrodes is set to 35 µm, which offers high sensitivity while maintaining a large enough detection volume for larger particles. The chosen distance between the electrodes and electrode lengths ensures that the device can analyze single particle to a concentration of approximately 10 7 particles/mL 31 . The microfluidic channels in the Design S are 200 μm wide and 50 μm high.…”

Thin flexible lab-on-a-film for impedimetric sensing in biomedical applications

“…The geometrical electrode configuration was first optimized in COMSOL Multiphysics software in our previous paper 34 . Notably, electrode geometry, i.e., width, position, and size of the gap between the electrodes, were optimized.…”