Tethered Particle Motion Biosensor for Drift-Free In-Vivo Monitoring

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Solution Overview

Problem

Current in-vivo biochemical sensing technologies, such as continuous glucose monitoring systems, face challenges with sensor drift requiring regular recalibration and the safety risks associated with unbound particles in in-vivo applications, making it difficult to implement bound-free separation processes effectively.

Innovation Solution

A biosensing technique based on tethered particle motion (TPM) where a functionalized particle attached by a tether to a surface changes between bound and unbound states in response to analyte presence, allowing for sensitive, specific, stable, and biocompatible monitoring without the need for frequent recalibration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If unbound particles are used in in-vivo biosensing, then the sensor can detect analytes, but safety risks increase and bound-free separation cannot be implemented

Engineering Contradiction:

ImprovesafetyVSAvoiddetection capability

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent introduces a tether as an intermediary element that connects the particle to the sensor surface. This tether allows the particle to remain bound to the surface while still enabling analyte detection through motion changes, thus eliminating safety risks of unbound particles while maintaining detection capability.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

Instead of using unbound particles for detection (conventional approach), the patent inverts the approach by using tethered particles that change their motion state upon analyte binding. The particle transitions from a relatively free motion state to a constrained state when bound to the analyte, providing detection without safety concerns.

Inventive Principle:

Principle #13The other way round (Inversion)

2Productivity

If enzymatic sensing is used for continuous glucose monitoring, then the sensor can continuously detect glucose, but sensor drift occurs requiring regular recalibration

Engineering Contradiction:

Improvecontinuous monitoring capabilityVSAvoidmeasurement stability

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent replaces enzymatic electrochemical sensing with a physical biosensing mechanism based on particle motion detection. By using tethered particles that change their motion characteristics when bound to analytes, the system eliminates sensor drift inherent in enzymatic systems while maintaining continuous monitoring capability.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent detects analytes by monitoring changes in the motion parameters of tethered particles. When particles bind to analytes, their diffusion characteristics change, providing a stable and drift-free measurement signal that enables continuous monitoring without recalibration.

Inventive Principle:

Principle #35Parameter changes

3Ease of operation

If tethered particles are used to avoid bound-free separation, then in-vivo applications become feasible, but particle binding to surface must be avoided to maintain sensitivity

Engineering Contradiction:

Improvein-vivo applicabilityVSAvoidsensitivity

Core Design Contradiction:

Ease of operationVSMeasurement precision

Solution Approach 1:

The patent exploits the dynamic motion of tethered particles in solution. The particles are free to move and diffuse when unbound to analytes, but their motion is constrained when bound. This dynamic behavior provides high sensitivity while maintaining in-vivo applicability through the tethered configuration.

Inventive Principle:

Principle #15Dynamics

Solution Approach 2:

The patent separates the binding function from the detection function. The tether provides a controlled connection to the surface, while the particle's motion characteristics provide the detection signal. This segmentation allows the particle to bind to analytes without non-specific binding to the surface, maintaining sensitivity.

Inventive Principle:

Principle #1Segmentation

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 enables continuous, reliable monitoring of analytes like glucose, electrolytes, and proteins with improved biocompatibility and reduced recalibration needs, suitable for in-vivo applications, while also being applicable for various diagnostics and research uses.

Implementation Method 1

Methodology Applied

Scientific EffectTethered particle motion:

Data Source

PatentUS11359231B2Biosensor based on a tethered particle

Publication Date: 2022.06.14 TECH UNIV EINDHOVEN

AI summary

A method for sensing an analyte uses tethered particle motion. A functionalized particle has a first state in which the functionalized particle is bound to the surface and a second state in which the functionalized particle is not bound to the surface, where the functionalized particle switches between the first and second states depending on the presence and absence of the analyte, thereby changing motion characteristics of the functionalized particle depending on the presence of the analyte. A spatial coordinate parameter of the functionalized particle is measured by a detector, and a processor determines the presence/concentration of the analyte from changes in the measured spatial coordinate parameter.