Locally Confined Chemistry at a CMOS Electrochemical Interface

Abstract

Chemical reactions are closely linked to one another through a network of equilibrium reactions, whose rates depend directly on the concentrations of the involved chemical species. Locally confining a chemical species of interest at a target concentration in a miniscule volume via electrochemical means enables parallelized control of the relevant chemical reactions across an array of electrochemical cells. Namely, as pH controls a myriad of chemical and biochemical processes in water, densely arrayed confinement of pH would enable their high-throughput studies and applications. Here, we present a 16 × 16 electrochemical cell array defined on and operated by a complementary metal-oxide-semiconductor (CMOS) integrated circuit. Each cell consists of a concentric pair of anode and cathode rings, where currents are injected with sub-nanoampere resolution to localize picoliters of acidic pH by making use of the quinone redox chemistry. The array also consists of open-circuit potential (OCP) sensors located within and in-between the cells for monitoring pH in real-time. To highlight the utility of arrayed pH localization, we parallelize pH-regulated enzymatic incorporation of nucleotides to single-stranded DNA molecules at any randomly selected set of cells. The site-specific enzymatic DNA elongation is enabled by local confinement of the pH-regulated DNA deprotection chemistry, which is directly controlled via electrochemical pH localization. Then, we expand the utility of this CMOS electrochemical pH localizer-imager array to analog computing using ions and molecules in an aqueous environment. We reconfigure the circuitry of the 16 x 16 electrochemical cell array into a 16 × 16 ionic transistor array, where we change the role of the center OCP sensor to an input voltage terminal. The current output at the input voltage terminal is a multiplication of the voltage input at the disk electrode and the weight parameter tuned by local confinement of H+ and benzoquinone concentrations. The disk current outputs are summated at the global pseudo-reference electrode, completing the analog multiply-accumulate (MAC) operation in water. This aqueous ionic circuit is a step toward sophisticated, low-power analog computing in water, like the biological signal processing performed by neuronal networks in the brain. Lastly, we review the semiconductor memory technologies and discuss them in terms of the tradeoff between speed and storage capacity. We propose how our arrayed pH localization technology can enable massively parallel enzymatic DNA synthesis for next-generation biomolecular data storage, whose theoretical data storage capacity is extremely high at the cost of being very slow.