Multi-Beam Resonator for Endotoxin Detection

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Solution Overview

Problem

Current methods for detecting endotoxins in samples, such as the rabbit pyrogen test and LAL-based tests, are either costly, require large quantities of reagents, or suffer from human interpretation errors, leading to potential false negatives and limited automation and sensitivity.

Innovation Solution

A multi-beam resonator device that continuously monitors changes in viscosity and density by tracking resonance frequency, quality factor, and phase angle of resonating beam members immersed in the sample, allowing for real-time detection of chemical reactions like gellation, agglutination, or coagulation, which indicates the presence of endotoxins.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If traditional LAL-based gel-clot tests are used to detect endotoxins, then the test can be performed with simple equipment, but the results require human interpretation which introduces errors and limits automation

Engineering Contradiction:
Improvesimplicity of equipmentVSAvoidautomation capability
Core Design Contradiction:
Ease of manufactureVSExtent of automation

Solution Approach 1:

The patent replaces optical/mechanical gel-clot detection with an electrochemical resonator-based system. The resonator measures changes in viscosity and density through electrical signals, enabling automated detection without human interpretation while maintaining equipment simplicity.

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

Solution Approach 2:

The patent introduces an electrochemical resonator as an intermediary between the sample and the detection system. The resonator translates physical changes (gelation, coagulation) into measurable electrical parameters (frequency, quality factor), enabling automation while keeping the overall system simple.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Device complexity

If vibration viscometers with single resonators are used to measure viscosity changes, then the device structure is simple, but the measurement precision and sensitivity are limited

Engineering Contradiction:
Improvedevice structureVSAvoidviscosity measurement precision
Core Design Contradiction:
Device complexityVSMeasurement precision

Solution Approach 1:

The patent divides a single resonator into multiple beam members (e.g., three beams). Each beam independently measures viscosity changes, and their combined signals provide enhanced measurement precision while maintaining relatively simple device structure through modular design.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent combines multiple resonator beams into a single integrated device. The beams work together to provide redundant and complementary measurements, improving overall measurement precision and reliability while keeping the device structure compact and manageable.

Inventive Principle:
Principle #5Merging (Combining)

3Productivity

If rapid detection methods are implemented to reduce analysis time, then throughput increases, but sensitivity and accuracy may be compromised

Engineering Contradiction:
ImprovethroughputVSAvoiddetection sensitivity
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent implements continuous real-time monitoring using the resonator system. Instead of discrete measurements, the system continuously tracks viscosity and density changes throughout the reaction process, enabling rapid detection without sacrificing sensitivity by capturing the complete temporal profile of the assay.

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

The patent uses the resonator's continuous output signals as feedback to monitor reaction progress in real-time. This enables early detection of endpoint events (gelation, coagulation) with high precision, allowing rapid throughput while maintaining accuracy through dynamic adjustment and real-time analysis.

Inventive Principle:
Principle #23Feedback

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, specificity, and throughput, providing quantitative results and reducing analysis time, with the ability to detect endotoxins in a sample within minutes, compared to traditional methods which can take hours.

Implementation Method 1

immersing at least one resonant beam member of a multi-beam resonator comprising at least 3 resonating beam members in the test sample mixture, and determining a change in viscosity and/or density of the test sample mixture by monitoring the change in at least one parameter relating to the resonance of at least one of the resonating beam members

Methodology Applied
Scientific EffectResonance: Resonance

Implementation Method 2

Vibration viscometers typically function by allowing the measurement of the dampening of an oscillating electrochemical resonator which is immersed in the fluid of which the viscosity is to be determined

Methodology Applied
Scientific EffectVibration: Vibration

Implementation Method 3

The measurement of the viscosity can be determined based on the drag caused by the relative motion of the fluid and surface

Methodology Applied
Scientific EffectDrag: Drag

Implementation Method 4

Vibration viscometers typically function by allowing the measurement of the dampening of an oscillating electrochemical resonator

Methodology Applied
Scientific EffectDamping: Damping

Implementation Method 5

a change in viscosity and/or density, by for example, gellation, precipitation, agglutination or coagulation, occurs

Methodology Applied
Scientific EffectGelation: Gel

Implementation Method 6

a change in viscosity and/or density, by for example, gellation, precipitation, agglutination or coagulation, occurs

Methodology Applied
Scientific EffectCoagulation: Coagulation

Data Source

PatentUS8689614B2Apparatus and method for determining the results of assays
Publication Date: 2014.04.08 HIGHLAND BIOSCI
  • US8689614B2 patent drawing
  • US8689614B2 patent drawing
  • US8689614B2 patent drawing

AI summary

The present invention provides a method for the real-time continuous monitoring of a change or density and/or viscosity within a test sample. Such methods can be used to determine the occurrence of a chemical reaction within a test sample where the same causes and increase or decrease in the density and/or viscosity of the sample due to, for example, a gelation, precipitation or coagulation occurring within the test sample. There is further provided a multi-resonator apparatus for use in measuring the density and/or viscosity of a test sample in which the multi-beam resonator is immersed.