ChemFET Electroscopic Imaging for Fast Live-Cell pH Response Mapping
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Solution Overview
Problem
Existing methods for analyzing cells on sensor arrays lack efficient and detailed electroscopic imaging capabilities to monitor cellular responses and metabolism, particularly for visualizing and analyzing cell electrophysiology and metabolism under various conditions or stimuli.
Innovation Solution
A ChemFET sensor array-based system is used to plate cells on a sensor array surface, capturing output signals as two-dimensional electroscopic images, which are processed to provide detailed insights into cell electrophysiology and metabolism by monitoring changes in surface potential and metabolic activities.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional microscopy methods are used to image cells, then cell morphology and structure can be observed, but the imaging process is time-consuming and requires extensive sample preparation
Solution Approach 1:
The patent extracts and measures the refractive index of cells directly in their native environment without requiring extraction, fixation, or staining procedures. By using electroscopic imaging to measure refractive index differences between cells and surrounding medium, the method eliminates time-consuming preparation steps while maintaining imaging capability.
Solution Approach 2:
The patent introduces an intermediary substance with a known refractive index between the cell and the imaging system. This intermediary allows for indirect measurement of cell refractive index through electroscopic imaging, enabling rapid imaging without direct contact or preparation of the cell sample.
2Measurement precision
If conventional staining methods are used to enhance cell visibility, then cell structures become more visible, but the staining process adds time and may alter cell properties
Solution Approach 1:
The patent removes the need for staining by directly measuring and exploiting the natural refractive index differences between cellular structures and their surroundings. This extraction of the staining function allows for time-efficient imaging while preserving cell integrity and native properties.
Solution Approach 2:
The patent utilizes refractive index differences (an optical property analogous to color in this context) to differentiate cell structures. By measuring how light bends when passing through different cellular components with varying refractive indices, the method achieves structure visualization without chemical stains.
3Stability of the object's composition
If fixed samples are used for imaging, then sample stability is improved, but the imaging process loses temporal resolution of dynamic cellular processes
Solution Approach 1:
The patent enables continuous, real-time imaging of living cells by measuring refractive index dynamically without interruption or fixation. The electroscopic imaging method allows for uninterrupted observation of cellular processes over time, maintaining both stability for measurement and temporal resolution for dynamics.
Solution Approach 2:
The patent allows living cells to maintain their own physiological state and continue their natural functions during imaging. By using non-invasive refractive index measurement, the cells serve themselves by providing inherent optical contrast through their metabolic activity and structural organization without external intervention.
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
The system enables high-resolution, subcellular analysis of cellular responses with frame rates in the sub-millisecond range, allowing for precise visualization and monitoring of cell electrophysiology and metabolism, even under varying conditions.
Implementation Method 1
an electrooscope that contacts the fluid and detects changes in capacitance
Implementation Method 2
detects changes in capacitance resulting from polarizability of cells
Implementation Method 3
detects changes in capacitance resulting from polarizability of cells
Data Source
Figure 1A
Figure 1B
Figure 1C
AI summary
Analyzing cells disposed on a sensor array surface of a ChemFET sensor array, may include flowing a solution having a step change in pH across the sensor array surface, wherein ChemFET sensors of the sensor array generate signals in response to the step change in pH to produce electroscopic image data. Multiple frames of the electroscopic image data are acquired during an acquisition time interval. Each frame corresponds to signal samples generated by the sensor array measured at a sampling time during the acquisition time interval. Each frame comprises pixels, wherein a given pixel in the frame corresponds to a signal sample from a given sensor in the sensor array. The electroscopic image data is segmented, based on characteristics of the signal samples, into cell regions corresponding to locations of the cells on the sensor array surface and background regions corresponding to areas on the sensor array having no cells.