Analyte Concentrator Microreactor for Biomarker Detection

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Solution Overview

Problem

Conventional capillary electrophoresis technologies face limitations in the detection and isolation of biomarkers due to low limits of detection and the complexity of sample preparation, particularly in handling small volumes and low concentrations of analytes in biological matrices.

Innovation Solution

A modular, portable, and interchangeable analyte concentrator-microreactor (ACM) device with immobilized affinity ligand groups is integrated into a capillary electrophoresis apparatus, enabling on-line preconcentration, microreactions, and separation of analytes, coupled with micro-valves for controlled fluid flow and a sealed system to prevent leakage.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional capillary electrophoresis is used for biomarker detection, then the system structure is simple, but the detection sensitivity and limit of detection are insufficient

Engineering Contradiction:
Improvedetection sensitivityVSAvoidsystem structure
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The system is divided into distinct functional modules: a separate ACM device module containing affinity ligand groups for analyte concentration, and a capillary electrophoresis module for separation and detection. This segmentation allows each module to be optimized independently, with the ACM module enhancing detection sensitivity through selective analyte concentration while the CE module maintains its simple structural design for separation.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The ACM device performs preliminary concentration and pre-separation of analytes before they enter the capillary electrophoresis system. By concentrating analytes of interest and removing interfering substances in advance, the system achieves higher detection sensitivity without requiring complex modifications to the CE detection system itself.

Inventive Principle:
Principle #10Preliminary action

2Ease of operation

If conventional sample preparation methods are used, then the procedure is simple, but the handling of small volumes and low concentrations is complex and error-prone

Engineering Contradiction:
Improvesample preparationVSAvoidanalyte concentration accuracy
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The ACM device performs self-service functions by automatically concentrating analytes and performing pre-separation without requiring manual intervention for complex sample preparation steps. The affinity ligand groups selectively bind target analytes, and the integrated microfluidic system handles concentration and transfer automatically, reducing operator error while improving concentration accuracy.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The system changes physical parameters within the ACM device to optimize analyte concentration and transfer. By controlling pH, ionic strength, and flow rates in the ACM module, the system achieves efficient analyte concentration from small volumes while maintaining ease of operation through automated parameter control.

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If analyte concentration is increased to improve detection, then the sensitivity improves, but the complexity of sample preparation increases

Engineering Contradiction:
Improvedetection sensitivityVSAvoidsample preparation complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The ACM device merges multiple functions—analyte concentration, pre-separation, and selective enrichment—into a single integrated module that couples directly to the capillary electrophoresis system. This consolidation achieves high analyte concentration for improved sensitivity without requiring separate, complex sample preparation steps, as all concentration and pre-processing functions are unified in one device.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The ACM device acts as an intermediary between the complex biological sample matrix and the capillary electrophoresis detection system. It selectively concentrates analytes of interest while removing interfering substances, serving as a mediator that simplifies the sample for CE analysis and improves detection sensitivity without transferring the complexity of sample preparation to the user.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 ACM device enhances the detection and isolation of biomarkers by improving sensitivity and specificity, allowing for the analysis of a wide range of analytes at various concentrations, reducing sample preparation errors, and enabling efficient processing of small sample volumes.

Implementation Method 1

The present invention provides a modular, portable, and interchangeable analyte concentrator-microreactor (ACM) device, containing one or more immobilized affinity ligand groups

Methodology Applied
Scientific EffectAffinity binding: Adsorption

Implementation Method 2

In one aspect of the invention, a sample containing one or more analytes of interest and/or their respective modified and/or altered corresponding counterpart is passed through an analyte concentrator-microreactor (ACM) device localized at the intersection point and connected to a transport capillary and to a separation capillary or channel. Furthermore, at or near the inlet and outlet ports of the transport and separation capillary or channel there are positioned four micro-valves

Methodology Applied
Scientific EffectValve control: Valve

Implementation Method 3

The present invention provides a modular, portable, and interchangeable analyte concentrator-microreactor (ACM) device that can be coupled or mounted to a cartridge-cassette of a capillary electrophoresis apparatus

Methodology Applied
Scientific EffectCapillary electrophoresis: Capillary Electrophoresis

Data Source

PatentUS9696299B2Integrated modular unit including an analyte concentrator microreactor device connected to a cartridge-cassette
Publication Date: 2017.07.04 PRINCETON BIOCHEMICALS INC
  • US9696299B2 patent drawing
  • US9696299B2 patent drawing
  • US9696299B2 patent drawing

AI summary

The integrated modular and interchangeable unit of the present invention comprises an analyte concentrator-microreactor (ACM) device having four entrance-exit ports identified as connection areas to a transport capillary for sample and buffer introduction, and to a separation capillary of a cartridge-cassette filled with an appropriate separation fluid for optimal separation of the analytes of interest. Affinity ligand groups are immobilized to microstructures contained within the main inner cavity or channel of the device or directly to the wall of the main inner channel for capturing one or more analytes. The inlet and outlet ends of the transport capillary are connected through a parallel design option to the analyte concentrator-microreactor (ACM) device to facilitate the path of sample and buffers through the inner cavity or channel of the analyte concentrator-microreactor (ACM) device.