Abstract
Here we present a planar patch clamp chip based on biomimetic cell membrane fusion. This architecture uses nanometer length-scale surface patterning to replicate the structure and function of membrane proteins, creating a gigaohm seal between the cell and a planar electrode array. The seal is generated passively during cell spreading, without the application of a vacuum to the cell surface. This interface can enable cell-attached and whole-cell recordings that are stable to 72 hours, and generates no visible damage to the cell. The electrodes can be very small (<5 μm) and closely packed, offering a high density platform for cellular measurement.
Highlights
We present a planar patch clamp chip based on biomimetic cell membrane fusion
In patch recording, maximizing the seal resistance is of critical importance for generating a high quality signal, with a gigaohm (>1 GΩ) resistance being the benchmark for a high quality patch
In an attempt to improve upon the slow and tedious nature of pipette patch clamping, many researchers have looked towards patch clamp chips, which consist of a multi-electrode array on a cell culture surface (Fig. 1A)
Summary
We present a planar patch clamp chip based on biomimetic cell membrane fusion. This architecture uses nanometer length-scale surface patterning to replicate the structure and function of membrane proteins, creating a gigaohm seal between the cell and a planar electrode array. In an even simpler patch chip implementation cells are cultured on flat, 2-dimensional electrode arrays With these platforms seal resistances are typically far too low (tens of MΩ1) to capture high quality cell data, as the liquid between the cell membrane and the culture surface acts as a current carrier (Fig. 1B). Many teams have increased cell leak resistances (Fig. 1B, Rseal) by making 3-dimensional structures that are engulfed by the cell, including wires[2,3], nano-mushrooms[4], and pits[5], which can increase the seal resistance into the hundreds of MΩ1 These 3-D structures increase the seal resistance by creating a tortuous path for current traveling in the liquid gap between the basal membrane and the culture surface. These results suggest that a new concept for sealing the gap between the cell membrane and the electrode surround is needed
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