CMOS Microelectrode Array for Local pH Sensing and Control

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Solution Overview

Problem

Existing electrochemical reaction systems face challenges in controlling and monitoring multiple reaction sites simultaneously due to complexity in ensuring uniform and precise conditions, particularly in dense micro-electrode arrays where proton diffusion is fast, making it difficult to achieve localized pH control for applications like DNA and peptide synthesis.

Innovation Solution

An electrochemical apparatus utilizing CMOS technology to create a semiconductor device with an array of microenvironments, each with individually addressable electrodes and circuitry for parallel electrical stimulation and monitoring, enabling precise control and sensing of local pH across a large number of sites.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If the number of reaction sites is increased to perform multiple electrochemical reactions in parallel, then productivity is improved, but device complexity increases due to difficulty in controlling and monitoring uniform conditions across the array

Engineering Contradiction:
Improveparallel reaction capacityVSAvoidcontrol and monitoring complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The system divides the reaction array into multiple independently controllable reaction sites, each with its own pH control and monitoring capabilities. This segmentation allows parallel processing while maintaining individual control over each site's conditions.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Each reaction site is equipped with pH sensing capability that provides real-time feedback on local pH conditions. This feedback mechanism enables automatic adjustment of pH at each site, simplifying the overall control complexity while maintaining precise control across the array.

Inventive Principle:
Principle #23Feedback

2Manufacturing precision

If dense localization of pH is achieved across a micro-electrode array, then manufacturing precision is improved for spatio-selective removal of protecting groups, but fast proton diffusion makes this very challenging

Engineering Contradiction:
Improvespatial pH localization precisionVSAvoidproton diffusion
Core Design Contradiction:
Manufacturing precisionVSObject-affected harmful factors

Solution Approach 1:

The system uses pH-sensitive electrodes as intermediaries to sense and control local pH conditions. These electrodes act as mediators between the bulk solution and the reaction sites, enabling precise pH control despite proton diffusion by continuously monitoring and adjusting local conditions.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces traditional mechanical or physical barriers used to confine protons with an electrochemical field-based approach. By using electric fields from pH-sensitive electrodes, the system achieves precise pH localization without relying on physical confinement structures that would be affected by proton diffusion.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

Enables precise, parallelized control and monitoring of local pH environments, facilitating efficient synthesis of macromolecules like DNA sequences by allowing independent control and sensing of thousands of microenvironments, improving the accuracy and scalability of electrochemical reactions.

Implementation Method 1

electrochemical apparatuses and methods for performing an electrochemical reaction and measuring electrical signals arising from the electrochemical reaction

Methodology Applied
Scientific EffectElectrochemical reaction: Electrolysis

Implementation Method 2

measuring electrical signals arising from the electrochemical reaction... monitoring each microenvironment's pH

Methodology Applied
Scientific EffectElectrical signal measurement for pH detection:

Data Source

PatentUS12631593B2Electrochemical measurement apparatuses and methods for monitoring and controlling pH
Publication Date: 2026.05.19 PRESIDENT & FELLOWS OF HARVARD COLLEGE
  • US12631593B2 patent drawing
  • US12631593B2 patent drawing
  • US12631593B2 patent drawing

AI summary

An electrochemical apparatus includes an array of pixels disposed on a chip, stimulator circuitry disposed on the chip and configured to provide electrical input signals to cause stimulation of the pixels of the array, and sensor circuitry disposed on the chip and configured to read electrical output signals from the pixels of the array. The stimulator circuitry is configured to provide the input signals to cause stimulation of the pixels individually, and the sensor circuitry is configured to selectively read the output signals from the pixels while the pixels are being stimulated. The sensor circuitry is configured to measure an open-circuit voltage at each of the pixels and a current flow at each of the pixels while the pixels are being stimulated by the stimulator circuitry. The open-circuit voltage may be measured while the current flow is being measured.