Pre-stimulated Biosensor Cells for Rapid Analyte Detection
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Solution Overview
Problem
Conventional biosensing systems using living cells as biosensors face limitations in specificity, susceptibility to cellular variability, reliance on reference compounds, and slow response times, making them difficult to automate and inefficient for detecting and quantifying target analytes in medical, food science, and environmental applications.
Innovation Solution
A method and system employing a sensor with a culture of photosensitive living cells attached to a surface, where a light source delivers pulses of light to induce changes in electrical impedance, allowing for the acquisition of impedance response time series to determine the presence and concentration of target analytes using an electrical impedance analyzer and computer system.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional biosensing systems use living cells as biosensors, then the system can detect target analytes, but the response time is slow (order of days) and automation is difficult
Solution Approach 1:
The patent applies preliminary action by pre-stimulating the living cells with a first compound (e.g., neurotransmitter or hormone) before introducing the target analyte. This pre-stimulation activates specific cellular pathways and receptors, putting the cells in a heightened state of responsiveness. When the target analyte is introduced, the cells respond much faster because the relevant signaling pathways are already activated, reducing the response time from days to minutes or hours while maintaining detection capability
Solution Approach 2:
The patent employs periodic action through a multi-stage measurement process: (1) pre-stimulation phase with first compound, (2) measurement phase with target analyte, (3) recovery phase, and (4) repeated cycles. This periodic approach allows the system to perform multiple measurements over time, improving both detection reliability and speed by capturing dynamic cellular responses at different stages rather than relying on a single slow endpoint measurement
2Measurement precision
If conventional biosensing systems use living cells as biosensors, then the system can detect target analytes, but the specificity is limited due to similar effects from different compounds
Solution Approach 1:
The patent applies segmentation by dividing the detection process into distinct phases: pre-stimulation with a specific first compound, exposure to target analyte, and measurement of impedance changes. By segmenting the process and using specific pre-stimulation compounds that activate particular cellular pathways, the system can distinguish between different analytes that might produce similar general cellular effects, thereby improving specificity while maintaining detection capability
Solution Approach 2:
The patent employs feedback mechanisms by monitoring impedance changes in real-time and using this information to determine analyte presence. The system measures the cellular response to pre-stimulation, then measures the response to the target analyte, and compares these signals. This feedback loop allows the system to distinguish specific analyte effects from non-specific cellular responses, improving specificity through comparative analysis of cellular behavior under different conditions
3Measurement precision
If conventional biosensing systems use living cells as biosensors, then the system can detect target analytes, but the system complexity increases and automation becomes difficult due to reliance on reference compounds
Solution Approach 1:
The patent applies self-service by using living cells that autonomously respond to chemical stimuli through their natural biological pathways. The cells themselves perform the complex recognition and signaling functions without requiring external reference compounds or complex calibration systems. The impedance measurement system simply detects the electrical changes resulting from cellular responses, simplifying the overall system architecture while maintaining high detection precision through the cells' inherent biological specificity
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 sensitivity, reduces analysis time, and facilitates automation, enabling the detection of low analyte concentrations and improved portability compared to conventional methods, with the ability to detect and quantify target analytes within an hour or less.
Implementation Method 1
The sensor comprises a culture of photosensitive living cells attached to a surface of the sensor
Implementation Method 2
employing an electrical impedance analyzer to acquire an impedance response time series comprising a plurality of values, wherein each value of the plurality of values is determined according to a measured electrical impedance of the sensor
Data Source
AI summary
Described systems and methods allow the detection and quantitation of a target analyte such as a toxin, drug, pesticide, etc. Some embodiments use a sensor comprising photo-sensitive cells, e.g., cells genetically modified to express an opsin. A light source such as an LED is used to optically stimulate the sensor cells, triggering changes in a measurable quantity such as the polarization of the cell membrane. Some embodiments use electrical impedance measurements to monitor the cell's recovery from the state induced by the optical stimulation. The recovery process is affected by the presence of certain bio-active compounds, which allows detection and quantitation of such compounds.