Developing A Mems Device for High-Throughput Multi-Parameter Single Cell Biophysical Analysis

Abstract

We introduced a MEMS device to perform direct measurements on electrical and mechanical properties of single cancer cells. Working in a continuous flow format permits high-throughput measurements. The device design allows us to define fixed or movable electrodes as part of the side-walls of an embedded microchannel. The stable air-liquid interface at micro-sized gaps between the electrodes and the channel wall provide flow continuity without causing any leakage problems. This unified processing approach allows us to define optimized electrode pattern configuration for both electrical and mechanical characterization areas. Moreover, the movable electrode is in direct contact with passing cells which enables direct sensing during compression. The device can perform both electrical and mechanical measurements on single cells in a continuous flow as demonstrated and also validated by optical control measurements. The proposed method aims at providing high-throughput biophysical cytometry, in an optics-and marker-free way, for cancer cell evaluation.

Fabricating Silicon Resonators for Analysing Biological Samples

“…Besides physical properties (e.g., mass or volume), these devices can also measure mechanical (e.g., stiffness and viscosity) and biological properties (e.g., cell growth). Although earlier demonstrations could not match the high throughputs of microfluidic-based cytometry techniques such as deformability cytometry, recent developments have demonstrated the potential to analyse hundreds of cells per second with only electrical readouts and without relying on imaging for analysis [97,144].…”

“…Similar to microgrippers, the majority of these devices are fabricated using dry etching (DRIE) of the silicon and wet etching of the buried oxide layer to release the moveable structures. Some devices need silicon-glass bonding [34], while some others use PDMS to form a channel [97]. In addition, several devices were fabricated with the PolyMUMPs TM process [95,98,99].…”

“…Polymer structures can also be used for similar channel-forming purposes. PDMS is a popular material to form channels or microwells [12,47,97,104] for handling biological samples.…”

“…A more recent study by Rezard et al attempted to perform mechanical characterisations in a high-throughput format with a design change in the compression side. Instead of using a movable tip, Rezard et al designed a wall that converged towards the sensing tip to form a gap smaller than the cell [97]. As a result, breast cancer cells in a continuous flow were compressed between the wall and the sensing tip while the stiffness of each passing cell was measured.…”

Frontiers in single cell analysis: multimodal technologies and their clinical perspectives

“…Another recent approach for detecting biophysical properties of single cells was developed by Rezard et al 92 By using micro-electro mechanical systems (MEMS) cells could be trapped and analysed for mechanical and electrical properties in real time during continuous flow.…”