Capacitive Aptamer Biosensor for Real-Time VEGF Detection

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Solution Overview

Problem

Current methods for measuring VEGF levels in vivo are limited by the lack of real-time, local detection and monitoring capabilities, which hinders the optimization of VEGF blockade therapies, particularly in cancer treatment.

Innovation Solution

A solid-state biosensor array using a capacitive platform with immobilized aptamers to detect VEGF molecules, enabling label-free, real-time monitoring of VEGF levels and trends, facilitating a closed feedback loop for regulating anti-angiogenic therapies.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional VEGF measurement methods are used, then VEGF levels can be measured, but real-time local detection and monitoring capabilities are lacking

Engineering Contradiction:
ImproveVEGF level detection accuracyVSAvoidreal-time monitoring capability
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent replaces traditional mechanical/chemical measurement systems with a solid-state capacitive biosensor that uses electrical field interactions. The aptamer-VEGF binding events are detected through changes in capacitance, enabling real-time monitoring without the time delays associated with conventional measurement methods.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The biosensor system performs self-detection and self-monitoring of VEGF levels continuously. The capacitive sensor automatically detects binding events as they occur, providing real-time feedback without requiring external intervention or periodic sampling, thus eliminating time loss in measurement.

Inventive Principle:
Principle #25Self-service

2Reliability

If continuous VEGF monitoring is implemented, then real-time feedback is available, but device complexity increases

Engineering Contradiction:
Improvecontinuous monitoring capabilityVSAvoidbiosensor system complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The solid-state capacitive platform serves multiple functions: it detects VEGF binding, provides real-time signal output, and can be integrated into various delivery systems. This multi-functionality reduces the need for separate components, thereby managing device complexity while maintaining continuous monitoring capability.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent utilizes changes in electrical parameters (capacitance) to detect VEGF binding events. By monitoring electrical field changes rather than using complex mechanical or optical systems, the device achieves reliable continuous monitoring with reduced structural complexity.

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If aptamer-based detection is used, then specific VEGF detection is achieved, but manufacturing complexity increases

Engineering Contradiction:
ImproveVEGF detection specificityVSAvoidbiosensor fabrication difficulty
Core Design Contradiction:
Measurement precisionVSEase of manufacture

Solution Approach 1:

The patent extracts only the essential detection function by using a simple capacitive structure with immobilized aptamers. By removing unnecessary components and focusing on the core detection mechanism, the system achieves high specificity while simplifying the manufacturing process compared to more complex biosensor designs.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The solid-state capacitive biosensor can be designed as a disposable or single-use device with pre-immobilized aptamers. This approach simplifies manufacturing by eliminating the need for complex calibration and maintenance systems, while maintaining high detection specificity through the stable aptamer-VEGF interaction.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

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 biosensor system provides accurate, continuous measurement of VEGF concentrations, enabling improved diagnosis and targeted delivery of chemotherapeutic agents, thereby enhancing tumor burden reduction and treatment efficacy.

Implementation Method 1

The sensor has an electrical polarity so as to naturally attract the intrinsically negative electric charge of VEGF molecules

Methodology Applied
Scientific EffectCapacitance: Capacitance

Implementation Method 2

The mechanism is based on an electrochemical binding of an aptamer suitable to bind to VEGF molecule

Methodology Applied
Scientific EffectElectrochemical binding:

Data Source

PatentEP2417440B1Method and apparatus for forming a homeostatic loop employing an aptamer biosensor
Publication Date: 2016.12.07 SENSOR KINESIS
  • EP2417440B1 patent drawingFigure 1
  • EP2417440B1 patent drawingFigure 1A
  • EP2417440B1 patent drawingFigure 2

AI summary

A novel architecture solid-state biosensor for label-free detection of vascular endothelial growth factor (VEGF) hybridization is presented. The new device is realized by forming a matrix array of parallel capacitors, thus allowing the realization of low-cost, portable, fully integrated devices. The detection mechanism is based on an electrochemical binding of circulating VEGF to an immobilized VEGF aptamer; whereby binding of these two compounds modulates the threshold voltage of a novel circuit, changing the impedance (capacitance) of the circuit. This novel circuit is further characterized by an electrode coded with a p-Si substrate, enhancing the affinity between the VEGF molecules and the aptamer. An apparatus forming a fluid cell is configured so as to enable the flow for delivering VEGF samples onto the active surface of the chip. The device has an array of parallel capacitors which act as an integrated, individual counter-electrode, computational apparatus which employs the sensory output over the time domain so as to enable detection, reporting and formation of a homeostatic loop for VEGF measurements. Moreover, this detector is able to provide an accurately measured and quantifiable rate of change of the VEGF molecules in- vivo, providing real time feedback of this important biomarker which may be used to measure response of the tumor to delivered chemotherapeutic agents and biological response modifiers (BRMs) for the purpose of determining tumor burden.