DNA origami placement could be used for high-resolution electrophysiological characterization and manipulation of neurons or other electrogenic cells. Such platforms are important since they enable fundamental studies as well as pharmacological screening. Further, such devices are essential for creating brain-machine interfaces for prosthetics, treating neurological disorders and advanced neuromorphic computing. Over the past few decade several platforms have been developed for this purpose: (a) massively parallel optical methods using ion or voltage sensitive dyes, (b) CMOS microelectrode arrays, (c) planar patch clamp arrays as well as (d) CMOS nanowire electrode arrays. While each of these platforms have progressively enabled higher spatio-temporal capabilities, they nonetheless have their own shortcomings. For instance, while optical methods can enable high-resolution interrogation of the electrical activity, optically triggering an electrical response require difficult genetic modification of the cells. The CMOS microelectrode arrays enables massively parallel recording though it's not highly sensitive since it's an extracellular method. Microfluidic planar patch clamp arrays, on the other hamd, allows high-sensitivity measurements although this method can't be made massively parallel. Finally, CMOS nanowire electrode arrays, is a relatively new technique, that can both be massively parallel as well as highly-sensitive. Although, the high aspect ratio electrodes can be challenging to fabricate and they can prove lethal for the cells. All things considered, it would be fair to state that much more work needs to be done to develop a general purpose platform for high-resolution electrophysiological experiments.
Fig (Synthetic synapse) outlines the schematics for fabricating a DNA origami based platform for electrophysiological studies. The designed platform consists of an array of femoliter chambers of well defined dimensions at the bottom which there is single DNA origami on top of a planar FET with connected to underlying CMOS integrated circuit. Further, each DNA origami could be designed to carry a defined number molecules to "interface" with the cells that are immobilized on top. The first method for cellular interface could be an artificial DNA nanopore (Fig (Synthetic synapse) d) designed to created a geometrically well defined leaky pore. By controlling the number, and density, of these pores precise control over the of interface would be possible. The second approach could be one using aptamers or antibodies to capture and localize specific ion channels (Fig (Synthetic synapse) e) as they are undergoing lateral diffusion on the surface of the cell. In addition to digitally controlling the total number of ion channels that could be interfacing with the FET, this method could allows study the behavior of specific ionic currents. One of the distinguishing features of our device is its close resemblance to naturally occurring electrical synapse (Fig (Synthetic synapse) c)
Synthetic synapse: (a) Schematic showing the fabrication of the “synthetic synapse” starting with an array of transistors on top of which DNA origami are localized, followed by creation of femotoliter chambers, attachment of DNA nanopores and finally plating of the cells; (b) Cross-section view of a single synthatic synapse or ‘pixel’ with a transistor, DNA origami and nanopore interfacing with the cell at a defined distance; (c) is a cartoon of a natural electrical synapse connecting two neurons through bi-directional gap-junction ion channels; (d) is a schematic of DNA nanopore created from a small six helix bundle with a hydrophobic belt created by attached 30 hydrophobic moeities; (e) is a schematic of second approach to cellular interface where an antibody or aptamer is used to recruit a specific natural ion channel undergoing lateral diffusion on the cell surface.