US-12618825-B2 - Biological sensing system having micro-electrode array

Abstract

A biological sensing system, comprising a microelectrode array having a plurality of islands that are thermally isolated from each other and are interconnected by flexible nano-scale wires. An embedded complementary metal oxide semiconductor (CMOS) instrumentation amplifier and wireless communication circuitry may be operatively connected to the microelectrode array and embedded within input/output pads connected to the wires at the periphery of the array.

Inventors

• Hossein Pajouhi
• Saeed Mohammadi
• Mojgan Sarmadi

Assignees

• PURDUE RESEARCH FOUNDATION

Dates

Publication Date

20260505

Application Date

20230414

Claims (4)

1. 1 . A method of forming a biological sensing system, comprising: providing a CMOS chip, the chip comprising an array of first metal regions in a top layer of the chip and a plurality of second metal regions, the second metal regions having a meandering shape interconnecting areas below the first metal regions; applying an anisotropic dry etching using Inductively Coupled Plasma (ICP), wherein the first metal regions provide masking to form an array of islands in the chip; depositing a metal oxide layer on sidewalls of the islands to form a protective barrier; further etching regions between the islands to form an etched region under the interior islands of the array, leaving only the second metal regions mechanically interconnecting the interior islands.
2. 2 . The method of claim 1 , further comprising transfer-printing the array onto a substrate.
3. 3 . The method of claim 2 , wherein the transfer-printing is performed using polydimethylsiloxane as a soft stamp to retrieve the array from the chip.
4. 4 . The method of claim 1 , wherein the second metal regions mechanically and electrically interconnect the interior islands.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS The present patent application is a divisional of U.S. patent application Ser. No. 15/815,700 filed Nov. 16, 2017, which is related to and claims the priority benefit of U.S. Provisional Patent Application Ser. No. 62/423,199, filed Nov. 16, 2016, the contents of which are hereby incorporated by reference in their entireties into the present disclosure. TECHNICAL FIELD The present disclosure generally relates to biological sensors, and in particular to a biological sensing system having a microelectrode array. BACKGROUND This section introduces aspects that may help facilitate a better understanding of the disclosure. Accordingly, these statements are to be read in this light and are not to be understood as admissions about what is or is not prior art. Biological sensing at micro- and nano-scales facilitated by high performance electrodes leads to a better understanding of single cell behavior. A variety of such electrodes have been developed to record electrical activities of beating cells, using both intracellular and extracellular techniques. A planar high-density microelectrode array (MEA) is an example of such electrodes utilized in an extracellular in-vitro measurement for interfacing to neurons. Moreover, nanoscopic probes, such as nanopillar electrode arrays, are extensively used for intracellular action potential measurement of individual neurons. The weak nature of biological signals combined with three-dimensional moving surfaces of cells and tissues demand tight integration of an array of flexible electrodes with electronic amplifier circuits to enhance the recovery of such signals. While novel flexible electronic sensors with improved sensitivities have been developed, they still require a number of leads coming out of the sensor array and in some cases require external instrumentation amplifiers for signal recovery. Such designs not only lead to loss of the overall sensitivity and reduced measurement bandwidth but also demand complex integration and packaging approaches. At the cellular level, three-dimensional kinked nanowire FETs have been proposed for single cell action potential recording. The kinked nanowire based designs have achieved high sensitivity at the sensor level, but require external amplifiers with associated path loss and undesired coupling, compromising their overall sensitivity. At the tissue level, three-dimensional flexible circuits on deformable sheets that bend according to the curvatures of tissues, provide interface for in-vivo characterization. While these techniques have utilized simple integrated electronics, they can benefit from large scale integration in order to reduce the distance among array sensors, further reducing the number of leads coming out of the array (analog multiplexing) and enhancing detected signals achieved by analog and digital signal processing and amplification. Prior art flexible electronic circuits are typically based on either thinned-down Si flakes that can only bend at a few millimeter radius to prevent damage or transferred-printed silicon micro-islands, presumably characterized with low yield as device density increases. Therefore, improvements are needed in the field. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1(a) shows the SEM images of a microarray structure on a CMOS SOI chip. FIG. 1(b) shows microarray islands after a plasma etch and before release. FIG. 1(c) shows a released microelectrode array. FIG. 1(d) shows the chip after the release of the microelectrode array. FIG. 2(a) shows a CMOS chip after fabrication in a foundry according to one embodiment. FIG. 2(b) shows anisotropic dry etching using ICP. FIG. 2(c) shows aluminum oxide deposition followed by ICP anisotropic etching and XeF2 isotropic etching. The SOI Oxide layer (buried oxide) served as intrinsic etch-stop to protect the island from the bottom. FIG. 2(d) shows transfer of the array using a PDMS transfer-printing technique. FIG. 2(e) shows a zoomed-in schematic of two cells of the array and the nanowire interconnects. FIG. 3(a) shows a SEM micrograph illustrates the microelectrode array inside the FIB vacuum chamber. The tip is located on the surface of a micro island. FIG. 3 (b) shows a fluorescent microscope image of the array laminating on a 220 lm fluorescent micro-bead. FIG. 3(c) shows a SEM image which illustrates the bent array under the Nanorobotic tip force. FIG. 3(d) shows a false color SEM image of the microelectrode array transfer-printed on a florescent microsphere. Inset illustrates false color SEM image of the microelectrode array transfer-printed on a florescent microsphere. FIG. 4(a) shows an optical image illustrating the cell manipulation onto the microelectrode array using a micro-tweezer. FIG. 4(b) shows an SEM image of the microelectrode array covering a mouse female germline stem cell. FIG. 4(c) shows a schematic of the microelectrode array under strain and in wet condition. FIGS. 4(d) and 4(e) show optical