Membrane-Engineered Cellular Biosensors for Selective Analyte Detection

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Solution Overview

Problem

Cellular biosensors based on genetic modification often suffer from poor selectivity and are not universally applicable due to transient transfections and limitations in cell line transfection, limiting their scope of application.

Innovation Solution

The method involves modifying cell surfaces by artificial insertion of molecules using electroinsertion to create membrane-engineered cells that react selectively with analytes, allowing for the use of receptor-like molecules such as proteins, nucleic acids, or lipids, which can be inserted at high density and from various sources, enabling specific interactions and combined reactions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If genetic modification (transfection) is used to improve selectivity of cellular biosensors, then selectivity is improved, but applicability is limited due to transient transfections and cell line limitations

Engineering Contradiction:
ImproveselectivityVSAvoidapplicability
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent introduces an intermediary substance (receptor-like molecule) that mediates between the cell membrane and the analyte. Instead of modifying the cell's genetic material, receptor-like molecules are artificially inserted into the cell membrane to provide selective binding capability. This intermediary approach allows any cell type to be used as a biosensor platform, overcoming the limitations of genetic transfection while maintaining high selectivity.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If receptor-like molecules are inserted at high density into cell membranes, then sensitivity is improved, but manufacturing complexity increases

Engineering Contradiction:
ImprovesensitivityVSAvoidmanufacturing complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent employs electroinsertion technology that allows receptor-like molecules to self-organize and insert into the cell membrane autonomously under an electric field. The cells themselves serve as the insertion medium, eliminating the need for complex external immobilization systems or matrices. This self-service mechanism simplifies manufacturing while enabling high-density receptor insertion that enhances sensitivity.

Inventive Principle:
Principle #25Self-service

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

This approach enhances selectivity and sensitivity, allowing for rapid, cost-effective detection of compounds with improved stability and versatility, suitable for various applications including disease diagnosis and environmental monitoring, with the ability to construct biosensors quickly without prior knowledge of compound interactions.

Implementation Method 1

modifying cell surfaces by artificial insertion of molecules using electroinsertion

Methodology Applied
Scientific EffectElectroinsertion:

Data Source

PatentEP1974211B1Molecular identification through membrane-engineered cells
Publication Date: 2017.09.20 KINTZIOS SPYRIDON
  • EP1974211B1 patent drawingFigure 1

AI summary

The present invention relates to the development of analytical devises based on one or more cells (cellular biosensors) the surface of which has been modified by the artificial insertion of molecules that can react specifically with analytes under determination. These receptor molecules may be proteins (such as enzymes, antigens or antibodies), nucleic acids, carbohydrates, lipids or belong to any other chemical group able to react specifically with target molecules (=analytes=) under determination in one or more samples. The introduction of these molecules into the cell surface can be achieved by electroinsertion or any other appropriate method. Different types of molecules can be inserted into the surface of the same cell, particularly if this contributes to the selectivity of the reaction with the analytes under determination. The method includes the use of an appropriate biosensor containing the modified cellular material in free state or immobilized in a gel or on a substrate made of appropriate material, so that the measurement of the selective reaction with the analyte under determination is ensured. The measurement of the reaction can be achieved by any appropriated method related to a physical chemical property of the sensor, such as the measurement of the change of the electric potential or various optical properties (such as fluorescence, chemiluminescence or electrogenerated chemiluminescence). Consequently, the determination of a chemical or biological compound is possible provided that the pattern of a certain physical chemical property of the biosensor in response to various concentrations of this compound is known, relative to other compounds of similar structure or function.