Microparticle-Based Bio-Element Detection in Microcavity Arrays

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Solution Overview

Problem

Current methods for detecting and isolating specific biological elements from large populations are inefficient, often resulting in loss of potential candidates and difficulty in deconvoluting mixed signals, with limitations in high-throughput screening and precise isolation of small cell populations.

Innovation Solution

A method utilizing microparticles that accumulate at detection surfaces to inhibit electromagnetic radiation, allowing for the detection and isolation of specific biological elements through the use of labels and forces such as gravitational, magnetic, or acoustic forces, enabling the identification of rare cells in complex mixtures within microcavity arrays.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional screening methods are used to detect biological elements in large populations, then the screening process can be performed, but the detection precision and ability to identify rare cells is insufficient

Engineering Contradiction:
Improvedetection precisionVSAvoidpopulation size
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent divides the large biological population into many small microcavities, with each cavity containing a small volume of sample and enabling individual detection. This segmentation allows rare cells to be isolated and detected with high precision while maintaining the ability to screen large populations in parallel.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces microparticles as intermediary elements that bind to target biological elements and provide detectable signals. These particles act as mediators between the rare target cells and the detection system, enhancing detection precision through signal amplification and optical contrast.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Ease of operation

If traditional cell isolation methods are applied to separate small populations of cells, then isolation can be achieved, but cellular function or activity may be modified

Engineering Contradiction:
Improveisolation easeVSAvoidcellular function integrity
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent replaces traditional mechanical isolation methods (such as centrifugation, filtration, or manual picking) with optical detection and magnetic particle-based separation. This substitution allows cells to be identified and isolated based on their intrinsic biological properties without physical stress that could alter cellular function.

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

Solution Approach 2:

The detection method relies on the natural properties of the cells themselves (such as endogenous fluorescence, enzyme activity, or surface markers) to generate detectable signals. Cells are isolated based on their own characteristics rather than requiring external manipulation, preserving their functional integrity.

Inventive Principle:
Principle #25Self-service

3Loss of information

If spatial addressing techniques are used to maintain identity of screened components, then specific clones can be identified, but high throughput screening and rapid isolation are not facilitated

Engineering Contradiction:
Improvecomponent identityVSAvoidscreening throughput
Core Design Contradiction:
Loss of informationVSProductivity

Solution Approach 1:

The patent adds the dimension of spatial organization by arranging microcavities in structured arrays, while simultaneously enabling high throughput through parallel processing. Each microcavity serves as a discrete addressable unit, and thousands of cavities can be screened simultaneously, achieving both identity preservation and high productivity.

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

Solution Approach 2:

The patent combines spatial addressing with parallel screening capabilities by integrating multiple detection functions into a unified microcavity array system. The system merges the advantages of individual cell isolation with high-throughput screening, allowing rapid isolation of multiple specific clones simultaneously.

Inventive Principle:
Principle #5Merging (Combining)

4Reliability

If phage display and repeated panning steps are used for library screening, then desired clones can be enriched, but time is consumed and potential binding candidates are lost

Engineering Contradiction:
Improveclone enrichmentVSAvoidscreening time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent performs preliminary enrichment and selection within the microcavity array before final detection, allowing desired clones to be pre-concentrated in their respective cavities. This preliminary action reduces the need for repeated panning steps and accelerates the overall screening process while maintaining enrichment reliability.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent skips the traditional multiple sequential panning steps by implementing a streamlined detection approach where rare cells are directly identified and isolated in a single operation. The rapid detection method rushes through the screening process by leveraging optical detection and magnetic separation to achieve enrichment without iterative manipulation.

Inventive Principle:
Principle #21Skipping (Rushing through)

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 scalable single-cell analysis, high-sensitivity detection of rare biological elements, and independent recovery of target cells, facilitating rapid disease diagnostics and therapeutics by simplifying the screening of millions of biological interactions in parallel.

Implementation Method 1

the ability of microparticles in a sample to partially or completely inhibit the transmission of electromagnetic radiation into and out of the sample through a detection surface

Methodology Applied
Scientific EffectElectromagnetic radiation absorption/inhibition: Absorption (EM radiation)

Implementation Method 2

The first particles may accumulate at the detection surface as a result of a force applied to the sample, wherein the force is selected from gravitational, magnetic, electrical, centrifugal, convective and acoustic forces

Methodology Applied
Scientific EffectMagnetic force: Magnetic Field

Implementation Method 3

a first label that emits electromagnetic radiation

Methodology Applied
Scientific EffectElectromagnetic radiation emission: Fluorescence

Data Source

PatentUS12105108B2Scalable bio-element analysis
Publication Date: 2024.10.01 THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV
  • US12105108B2 patent drawing
  • US12105108B2 patent drawing
  • US12105108B2 patent drawing

AI summary

A method is provided for detecting one or more analytes in a sample. The method relies, in part, on the ability of functionalized particles added to the sample to partially or completely inhibit the transmission of electromagnetic radiation into and out of the sample through a detection surface in a reaction vessel containing the sample. In a microarray format, the invention can be used to screen millions, billions or more biological elements, such as an organism, cell, protein, nucleic acid, lipid, saccharide, metabolite, or small molecules. Methods, apparatuses and kits are described.