Wax-Microsphere Matrix for Controlled Reagent Release in Sequencing

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Solution Overview

Problem

Current sequencing technologies face inefficiencies in sample preparation due to difficulties in handling microspheres within cartridges, electrostatic cling to surfaces, and challenges in reagent dissolution and purification, leading to complex and costly workflows.

Innovation Solution

A method involving a wax-microsphere matrix is used to encapsulate lyophilized microspheres, which are rehydrated and separated by controlled temperature changes, allowing for efficient release and handling of reagents for sequencing processes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If lyophilized microspheres are handled directly in cartridges, then reagent delivery is possible, but electrostatic cling to surfaces occurs and handling becomes difficult

Engineering Contradiction:
Improvemicrosphere handlingVSAvoidelectrostatic cling
Core Design Contradiction:
Ease of operationVSObject-affected harmful factors

Solution Approach 1:

A wax matrix is introduced as an intermediary carrier to encapsulate the lyophilized microspheres. The wax matrix prevents direct contact between microspheres and cartridge surfaces, thereby eliminating electrostatic cling issues while maintaining controlled reagent delivery capability.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The microsphere reagent is segmented into two functional components: the lyophilized microsphere containing the active reagent and the wax matrix providing handling benefits. This segmentation allows each component to fulfill its specific function independently - the microsphere for reagent activity and the wax for electrostatic protection.

Inventive Principle:
Principle #1Segmentation

2Device complexity

If multiple reagents are dissolved in a common well, then workflow is simplified, but staggering dissolution and differentiation of reagents becomes difficult

Engineering Contradiction:
Improveworkflow complexityVSAvoidreagent dissolution control
Core Design Contradiction:
Device complexityVSDifficulty of detecting and measuring

Solution Approach 1:

Each reagent is pre-encapsulated in its own lyophilized microsphere before being incorporated into the wax matrix. This preliminary encapsulation allows for controlled, sequential dissolution of individual reagents by simply controlling the dissolution rate of each microsphere, eliminating the need to manage complex dissolution timing of multiple separate reagents.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

Different reagents are placed in different microspheres within the same wax matrix, creating local differentiation. Each microsphere maintains its own dissolution characteristics, allowing individual reagents to dissolve at different rates or times while being contained in a common well environment.

Inventive Principle:
Principle #3Local quality

3Reliability

If sample preparation involves multiple steps and material transfers, then sequencing accuracy can be maintained, but the process becomes tedious and expensive

Engineering Contradiction:
Improvesequencing accuracyVSAvoidsample preparation efficiency
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

Multiple reagents that would traditionally require separate handling steps are merged into a single wax matrix containing multiple lyophilized microspheres. This consolidation eliminates multiple material transfer steps while maintaining the reliability of each reagent through its protected encapsulation, thereby improving productivity without sacrificing sequencing accuracy.

Inventive Principle:
Principle #5Merging (Combining)

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 simplifies workflows by enabling predictable microsphere rehydration and reagent release, improving stability and efficiency in sequencing processes.

Implementation Method 1

exposing said composition comprising said wax-microsphere matrix to said first melt-condition melts the wax component

Methodology Applied
Scientific EffectMelting: Melting

Implementation Method 2

exposing said composition to a first release-condition to rehydrate at least one lyophilised microsphere

Methodology Applied
Scientific EffectRehydration: Absorption (physical)

Implementation Method 3

exposing said at least one rehydrated lyophilised microsphere to a separation-condition to separate said wax component from said at least one rehydrated lyophilised microsphere

Methodology Applied
Scientific EffectPhase separation: Phase Change

Data Source

PatentUS12577479B2Wax-microsphere matrix compositions and methods of making and using the same
Publication Date: 2026.03.17 ILLUMINA CAMBRIDGE LTD
  • US12577479B2 patent drawing
  • US12577479B2 patent drawing
  • US12577479B2 patent drawing

AI summary

The present disclosure relates to a method including exposing a composition comprising a wax-microsphere matrix to a first melt-condition, wherein said wax-microsphere matrix comprises a wax component and a plurality of lyophilised microspheres, wherein said plurality of lyophilised microspheres comprise one or more reagent, whereby exposing said composition comprising said wax-microsphere matrix to said first melt-condition melts the wax component; exposing said composition to a first release-condition to rehydrate at least one lyophilised microsphere; and exposing said at least one rehydrated lyophilised microsphere to a separation-condition to separate said wax component from said at least one rehydrated lyophilised microsphere. Also disclosed are methods of preparing a wax-microsphere matrix and releasing one or more reagent from a wax-microsphere matrix as well as compositions. Also disclosed are cartridges with a reagent reservoir including the compositions described herein. Also disclosed are systems for controlling release of one or more reagent including the compositions described herein.