Miniaturized DNA Microarray Segmentation for Low-Volume Hybridization

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Solution Overview

Problem

Conventional DNA microarray assays face limitations such as lengthy incubation times, large sample volumes, lack of sample conservation, and separate optical readout requirements, which hinder efficient and miniaturized sample processing.

Innovation Solution

The development of miniaturized DNA microarrays with high-density oligonucleotide probes on a small optically transparent substrate, integrated with microfluidics and optical readout capabilities, allowing for controlled fluid flow and sample recovery within a sealed chamber, enabling low-volume analysis and high specificity hybridization reactions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional DNA microarray assays use standard-size solid supports, then optical detection can be performed, but the incubation time becomes lengthy and large sample volumes are required

Engineering Contradiction:
Improvedetection capabilityVSAvoidincubation time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The conventional large microarray slide is segmented into multiple smaller microarray substrates, each containing a subset of probes. This segmentation increases the surface-area-to-volume ratio, improving hybridization efficiency and reducing incubation time while maintaining detection capability through arrayed coverage of the full probe set across multiple substrates.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention transitions from a single large 2D microarray surface to multiple smaller 2D surfaces arranged in a 3D configuration (e.g., stacked or arrayed in wells). This dimensional change allows simultaneous hybridization reactions to occur in parallel across multiple substrates, reducing total incubation time while preserving comprehensive detection coverage.

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

2Measurement precision

If conventional DNA microarray assays use standard-size solid supports, then probe coverage can be comprehensive, but large target sample volumes are required

Engineering Contradiction:
Improveprobe coverageVSAvoidsample volume
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The comprehensive probe set is segmented across multiple smaller substrates, each requiring minimal sample volume for hybridization. The segmented approach allows the same comprehensive probe coverage to be achieved with fractioned sample volumes distributed across parallel reactions, reducing total sample consumption.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Each individual microarray substrate contains only a partial set of probes rather than the complete array, allowing hybridization reactions to proceed with reduced sample volumes. The partial probe sets on multiple substrates collectively provide comprehensive coverage when results are integrated, eliminating the need for excessive sample volumes required by single large arrays.

Inventive Principle:
Principle #16Partial or excessive action

3Reliability

If conventional DNA microarray assays are performed, then hybridization reactions can occur, but no effort is made to conserve or recover the sample

Engineering Contradiction:
Improvehybridization reactionVSAvoidsample conservation
Core Design Contradiction:
ReliabilityVSLoss of substance

Solution Approach 1:

The microarray substrates are designed to be removable from the reaction vessels after hybridization, allowing the sample solution to be recovered and retained for downstream applications. This recovering approach maintains reaction reliability while preventing sample loss, as the sample can be reused for additional assays or analysis after the microarray reading is complete.

Inventive Principle:
Principle #34Discarding and recovering

4Measurement precision

If conventional DNA microarray assays use separate optical readout, then detection can be performed, but specialized scanners are required and the process becomes complex

Engineering Contradiction:
Improvedetection accuracyVSAvoidreadout system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The microarray substrates are designed with universal features (such as standardized barcodes or fluorescent markers) that enable detection using common imaging equipment rather than specialized scanners. This multi-functionality approach maintains detection accuracy while reducing device complexity by allowing standard microscopes or plate readers to perform readout.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The invention introduces intermediary detection elements (such as fluorescently labeled probes or barcode identifiers) that mediate between the hybridization event and the detection system. These intermediaries translate biological hybridization signals into optical signals detectable by standard equipment, maintaining measurement precision while eliminating the need for complex specialized scanning systems.

Inventive Principle:
Principle #24Intermediary (Mediator)

5Quantity of substance

If miniaturized microarrays are used, then sample volume is reduced, but the array density must be increased to maintain probe coverage

Engineering Contradiction:
Improvesample volumeVSAvoidarray density
Core Design Contradiction:
Quantity of substanceVSManufacturing precision

Solution Approach 1:

The comprehensive probe set is segmented across multiple miniaturized substrates rather than attempting to fit all probes on a single small substrate. This segmentation allows each mini-array to use moderate-density probe placement while collectively providing full probe coverage across the array set, reducing the manufacturing precision requirements for individual substrates.

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 reduces incubation time, conserves sample volume, and allows for high specificity and sensitivity in DNA hybridization detection, with the ability to recover unhybridized samples for further analysis, while maintaining the advantages of traditional microarray assays.

Implementation Method 1

the probe and target DNA will hybridize and this hybridization reaction is generally detected optically

Methodology Applied
Scientific EffectHybridization: Chemical Bonding

Implementation Method 2

in other instances capillary action can draw the fluid into the assembly

Methodology Applied
Scientific EffectCapillary action: Capillary Action

Data Source

PatentUS11890620B2Miniaturized DNA microarray for small-volume sample processing
Publication Date: 2024.02.06 THE CHARLES STARK DRAPER LABORATORY INC
  • US11890620B2 patent drawing
  • US11890620B2 patent drawing
  • US11890620B2 patent drawing

AI summary

Miniaturized DNA microarrays are described to be used in conjunction with microfluidic channels or microcentrifuge tubes and microcentrifuge filters to reduce sample size, incubation time and to increase overall binding efficiency.