Ring Electrode Quartz Crystal Resonator for Uniform CTC Detection

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Solution Overview

Problem

Quartz crystal resonators (QCRs) face limitations in mass sensitivity distribution due to Gaussian distribution profiles, which affect their ability to detect circulating tumor cells (CTCs) effectively, as the sensitivity is higher at the center and decreases towards the edges of the electrode, leading to challenges in uniform detection and isolation of CTCs.

Innovation Solution

The development of a ring electrode QCR design with a mathematical model to optimize mass sensitivity distribution, combined with surface modification using 3-aminopropyltriethoxysilane (APTES) and anti-EpCAM antibody immobilization, enhances the uniformity of mass sensitivity and improves CTC capture efficiency.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If a traditional keyhole electrode QCR design is used, then the device structure is simple and easy to manufacture, but the mass sensitivity distribution is non-uniform (Gaussian profile) with higher sensitivity at the center and lower sensitivity at the edges

Engineering Contradiction:
Improveease of manufactureVSAvoidmass sensitivity distribution uniformity
Core Design Contradiction:
Ease of manufactureVSManufacturing precision

Solution Approach 1:

The electrode is segmented into multiple independent ring-shaped electrodes arranged concentrically on the QCR surface. This segmentation allows each ring to contribute differently to the overall sensitivity distribution, enabling the creation of a more uniform mass sensitivity profile across the sensing area compared to a single keyhole electrode design.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Different regions of the QCR surface are given different electrode configurations with varying inner and outer radii. The ring electrodes are positioned and sized to create zones of enhanced sensitivity at the edges while maintaining adequate sensitivity at the center, thereby achieving local optimization of mass sensitivity distribution.

Inventive Principle:
Principle #3Local quality

2Measurement precision

If the electrode area is increased to improve CTC detection capability, then the detection sensitivity improves, but the non-uniform Gaussian distribution causes edge regions to have reduced sensitivity

Engineering Contradiction:
Improvedetection sensitivityVSAvoidmass sensitivity distribution uniformity
Core Design Contradiction:
Measurement precisionVSManufacturing precision

Solution Approach 1:

The large electrode area is divided into multiple ring-shaped segments that can be independently optimized. Each ring contributes to the overall detection capability while the distributed arrangement ensures more uniform sensitivity across the entire sensing area, preventing the edge effect problem in single large electrode designs.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The electrode design transitions from a traditional keyhole shape to a multi-ring concentric configuration, effectively utilizing the radial dimension of the QCR surface. This dimensional reorganization allows the electrode to cover a larger area while maintaining uniform sensitivity distribution through strategic placement of multiple rings at different radii.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

3Measurement precision

If surface modification with APTES and anti-EpCAM antibody is implemented, then CTC capture efficiency improves, but the fabrication process complexity increases

Engineering Contradiction:
ImproveCTC capture efficiencyVSAvoidfabrication process complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The QCR surface is pre-modified with APTES to introduce amine groups before antibody immobilization. This preliminary surface functionalization creates a stable foundation for subsequent antibody attachment, ensuring uniform and controlled distribution of anti-EpCAM antibodies across the ring electrode surfaces, which enhances CTC capture efficiency.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

APTES serves as an intermediary substance between the QCR surface and the anti-EpCAM antibodies. It forms a chemical bridge that facilitates stable and uniform antibody immobilization on the electrode surface, improving CTC capture while providing a systematic and controllable fabrication approach.

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 ring electrode QCR design achieves a more uniform mass sensitivity distribution and increased capture efficiency of CTCs, with a linear relationship between frequency shift and the number of attached cells, improving the detection and isolation of CTCs compared to traditional keyhole designs.

Implementation Method 1

Quartz crystal resonators (QCRs) have become a widely used analytical tool due to their sensitivity to mass variations as small as nanograms

Methodology Applied
Scientific EffectPiezoelectric effect: Piezoelectric Effect

Implementation Method 2

The resonators are designed to oscillate at a fundamental frequency via the piezoelectric effect when voltage is applied to the excitation electrodes

Methodology Applied
Scientific EffectResonance: Resonance

Implementation Method 3

In the 1950s, Sauerbrey theorized that adding or removing a small amount of mass from the surface of a quartz crystal electrode causes a shift in the resonance frequency

Methodology Applied
Scientific EffectMass-frequency relationship:

Data Source

PatentUS20240333256A1Design and fabrication of a novel sensor based on the quartz crystal resonator technique to detect biological and non-biological systems
Publication Date: 2024.10.03 THE BOARD OF TRUSTEES OF THE UNIV OF ARKANSAS
  • US20240333256A1 patent drawing
  • US20240333256A1 patent drawing
  • US20240333256A1 patent drawing

AI summary

A quartz crystal resonators (QCR) used as a sensor for quantitatively detection of a target. The QCR comprises a first electrode; a second electrode; a quartz wafer disposed between the first electrode and the second electrode; an immobilizing agent disposed on a surface of at least one of the first electrode and the second electrode; and a binding agent in association with the immobilizing agent; wherein the binding agent binds to the target.