CMOS Electrode Arrays for Label-Free Cell Mapping and Adhesion
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Solution Overview
Problem
Existing technologies face challenges in efficiently and non-invasively mapping and manipulating cells on semiconductor substrates, particularly in detecting cell presence and adhesion using electrode arrays, as traditional impedance measurements are not sensitive to cell presence and require invasive methods.
Innovation Solution
Utilizing a CMOS-compatible electrode array with cross-electrode impedance measurements and CMOS circuitry to detect cell presence and adhesion by measuring cross-electrode impedance, which is affected by the presence of cells, allowing for high spatial-resolution assessment and real-time electrical stimulation and recording.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional impedance measurements are used to detect cell presence, then the measurement method is simple, but the sensitivity to cell presence is insufficient and invasive methods are required
Solution Approach 1:
The patent segments the measurement process by introducing multiple electrodes arranged in arrays rather than using single electrode impedance measurements. This segmentation allows for differential measurements that specifically detect cell presence by comparing potentials between multiple electrodes, thereby increasing sensitivity while maintaining practical device implementation
Solution Approach 2:
The patent uses the electrolyte solution as an intermediary medium that conducts electrical signals between multiple electrodes. By measuring potential differences through this intermediary, the system can detect cell presence indirectly through changes in electrical properties of the solution, achieving high sensitivity without direct contact with cells
2Manufacturing precision
If electrode arrays with small pitch are used to achieve high spatial resolution, then the mapping resolution is improved, but the device complexity and manufacturing difficulty increase
Solution Approach 1:
The patent employs CMOS circuitry that serves multiple functions: it generates stimulus signals, records electrical responses, and processes data. This multi-functionality allows the same integrated circuit technology to achieve high spatial resolution electrode arrays while simplifying manufacturing by using standard CMOS fabrication processes rather than specialized high-precision electrode fabrication
Solution Approach 2:
The patent replaces mechanical/electrochemical electrode fabrication methods with CMOS semiconductor manufacturing. By using standard integrated circuit fabrication techniques to create the electrode arrays and associated circuitry, the system achieves high spatial resolution (small electrode pitch) while benefiting from the scalability and precision of semiconductor manufacturing
3Measurement precision
If invasive methods are used to detect cell adhesion, then the detection capability is sufficient, but the cell viability is affected
Solution Approach 1:
The patent enables cells to serve as their own indicators by measuring their natural electrical properties (membrane potential, ion channel activity) without requiring external labels or invasive interventions. The CMOS circuitry detects these self-generated electrical signals, allowing cell adhesion assessment that preserves cell viability while maintaining detection capability
Data Source
AI summary
Disclosed herein are an apparatus for electrically assessing and/or manipulating cells. One aspect is directed to electrically mapping cells on the surface of the semiconductor substrate via cross-electrode impedance measurements. Further according to some aspects, the electrode array allows for spatially addressable electrical stimulation and/or recording of electrical signals in real-time using the CMOS circuitry. Some of these aspects are directed to using an electrode array to perform cell patterning through electrochemical gas generation, and extracellular electrochemical mapping.