Spatiotemporal norepinephrine mapping using a high-density CMOS microelectrode array

Abstract

A high-density amperometric electrode array containing 8192 individually addressable platinum working electrodes with an integrated potentiostat fabricated using Complementary Metal Oxide Semiconductor (CMOS) processes is reported. The array was designed to enable electrochemical imaging of chemical gradients with high spatiotemporal resolution. Electrodes are arranged over a 2 mm × 2 mm surface area into 64 subarrays consisting of 128 individual Pt working electrodes as well as Pt pseudo-reference and auxiliary electrodes. Amperometric measurements of norepinephrine in tissue culture media were used to demonstrate the ability of the array to measure concentration gradients in complex media. Poly(dimethylsiloxane) microfluidics were incorporated to control the chemical concentrations in time and space, and the electrochemical response at each electrode was monitored to generate electrochemical heat maps, demonstrating the array's imaging capabilities. A temporal resolution of 10 ms can be achieved by simultaneously monitoring a single subarray of 128 electrodes. The entire 2 mm × 2 mm area can be electrochemically imaged in 64 seconds by cycling through all subarrays at a rate of 1 Hz per subarray. Monitoring diffusional transport of norepinephrine is used to demonstrate the spatiotemporal resolution capabilities of the system.

Advances and Perspectives in Chemical Imaging in Cellular Environments Using Electrochemical Methods

“…Moreover, this type of device further illustrates the possibility of chemical imaging in environments that SEPM is not feasible. Using 64 subarrays of 128 individual Pt working electrodes, high-density MEAs of 8192 individually addressable electrodes were created and used to map norepinephrine across a 2 × 2 mm area [138]. Temporal resolution was limited to 10 ms per subarray, or 64 s at a rate of 1 Hz per subarray.…”

“…It has been shown that flexible neural probes can be inserted into living tissue, with the assistance of a stiffener assembly, in a further example of an application of electrochemical imaging in a location inaccessible to standard SEPM methods operated with a mobile scanning probe [142]. Although this concept has Using 64 subarrays of 128 individual Pt working electrodes, high-density MEAs of 8192 individually addressable electrodes were created and used to map norepinephrine across a 2 × 2 mm area [138]. Temporal resolution was limited to 10 ms per subarray, or 64 s at a rate of 1 Hz per subarray.…”

From organotypic culture to body‐on‐a‐chip: A neuroendocrine perspective

“…Queval et al 125 Loughlin et al 76 Wydallis et al 85 Kim et al 114 Huang et al 121 Tedjo et al 86 Shah et al 115 Park et al 124 52 Despite these characterisations of the roller culture model, and its widespread use in studies of the hypothalamus among other brain regions, the model was not without its problems.…”

“…85 More recently, organotypic adrenal slices have been used to test the validity of a high-density electrochemical microelectrode array for assessing spatial and temporal dynamics of catecholamine release. 86,87 Independently, another group used tissue culture supernatants collected from 150-μm thick adrenal slices to measure changes in catecholamine secretion using high-performance liquid chromatography in response to acetylcholine, nicotine and hexamethonium. 88 This study did not provide temporal resolu-…”

Recent Advances in Biosensing for Neurotransmitters and Disease Biomarkers using Microelectrodes

“…There appeared to be a low research output on norepinephrine detection in recent literature. Wydallis et al . have published their findings on spatiotemporal norephinephrine mapping using an array of high‐density complementary metal oxide semiconductors.…”