Electrophoretic Analyte Capture for High-Resolution Spatial Mapping
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Solution Overview
Problem
Existing methods for capturing analytes from biological samples fail to provide spatial information about the position of single cells within a tissue and often result in low analyte capture due to insufficient permeabilization, leading to loss of spatial resolution and diffusive migration.
Innovation Solution
An electrophoretic system that uses a conductive substrate as an anode and a spaced cathode with a non-conductive spacer, applying a voltage to actively direct analytes to capture probes, reducing lateral diffusion and enhancing spatial resolution by ensuring precise migration and binding.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional analyte capture methods are used without electrophoresis, then the process is simpler, but spatial resolution is lost due to diffusive migration
Solution Approach 1:
The patent replaces passive diffusive migration with active electrophoretic migration using an electric field. The electric field actively directs analytes from the biological sample to capture probes on the substrate, eliminating random diffusive motion and preserving spatial information about analyte positions in the original sample.
Solution Approach 2:
The patent introduces an electric field as an intermediary mechanism to control analyte migration. The electric field serves as a controllable mediator that directs analyte movement in a predictable manner, replacing uncontrolled diffusion and enabling precise spatial mapping of analytes to their original positions in the tissue sample.
2Quantity of substance
If additional permeabilization processes are applied to increase analyte release, then more analytes are captured, but the sample structure is further disrupted
Solution Approach 1:
The patent replaces chemical/biological permeabilization processes with electrophoretic extraction. Instead of using chemicals to disrupt cell membranes and release analytes, the system uses an electric field to actively pull analytes through intact or minimally processed tissue structures, thereby maintaining sample integrity while achieving effective analyte capture.
3Speed
If the cathode is placed close to the substrate, then the electric field is stronger and analyte migration is faster, but lateral diffusion increases
Solution Approach 1:
The patent addresses the trade-off between migration speed and spatial resolution by optimizing the electric field geometry and strength. The system achieves rapid analyte migration while maintaining spatial fidelity by controlling field parameters and using the substrate-cathode configuration to minimize lateral diffusion components during the electrophoretic process.
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 improves spatial resolution by actively directing analytes to capture probes, increasing the amount captured and maintaining spatial fidelity without additional permeabilization processes, thus providing more accurate spatial information.
Implementation Method 1
an electric field created by the electrophoretic system can cause analytes to be released from the cell, and effectively migrate toward and bind to the capture probes attached to the substrate
Implementation Method 2
The electrophoretic system can apply a voltage between the electrodes (i.e., the substrate comprising the anode, and the electrode as the cathode) to cause analytes to release from the sample and migrate to capture probes attached to the substrate
Data Source
AI summary
An electrophoretic system is provided for analyte capture from a biological sample. The electrophoretic system can be used to permeabilize the sample to allow analytes to be released from the sample. For example, the sample can be contacted with capture probes attached to a substrate, and an electric field created by the electrophoretic system can cause analytes to be released from the cell, and effectively migrate toward and bind to the capture probes attached to the substrate.