Immiscible Fluid Slug Processing for Low-Volume Nucleic Acid Analysis

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Solution Overview

Problem

Current molecular biology procedures require large sample and reagent volumes, which are wasteful and inefficient, especially for nucleic acid analysis and sequencing, where standard methods consume excessive resources and are time-consuming.

Innovation Solution

The development of a system and method for processing discrete volumes of fluids, specifically using immiscible fluids such as aqueous and non-aqueous liquids in conduits, allowing for PCR amplification and sequencing in micro-liter sized volumes, enabling efficient handling and analysis of nucleic acids in small volumes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of substance

If standard molecular biology procedures are used, then nucleic acid analysis and sequencing can be performed, but large sample and reagent volumes are consumed which are wasteful and inefficient

Engineering Contradiction:
Improvereagent consumptionVSAvoidprocedural efficiency
Core Design Contradiction:
Loss of substanceVSProductivity

Solution Approach 1:

The system segments the continuous fluid stream into discrete immiscible-fluid-discrete-volumes (slugs) separated by spacing fluid. Each slug contains a specific volume of sample and reagents, allowing individual processing. This segmentation enables precise control of reagent volumes in each discrete volume, reducing overall reagent consumption while maintaining high throughput processing capability

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention changes the physical state and arrangement of fluids by using immiscible fluids to create discrete volumes instead of continuous processing. By altering the fluid configuration from continuous to discrete segmented volumes, the system achieves both reduced reagent consumption and efficient high-throughput processing, resolving the contradiction between substance loss and productivity

Inventive Principle:
Principle #35Parameter changes

2Productivity

If standard molecular biology procedures are used, then nucleic acid analysis can be performed, but excessive time is consumed making the process time-consuming

Engineering Contradiction:
Improveprocessing speedVSAvoidprocedural time
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The system maintains continuous flow of immiscible-fluid-discrete-volumes through the processing conduit while performing multiple operations. The continuous segmentation and processing of slugs eliminates idle time between samples, allowing parallel processing of multiple discrete volumes simultaneously, thereby increasing productivity without extending total procedural time

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

The system performs preliminary segmentation of samples into discrete immiscible-fluid-discrete-volumes before processing. This pre-segmentation allows all subsequent processing steps to occur in parallel across multiple discrete volumes simultaneously, significantly reducing total procedural time while maintaining high processing speed

Inventive Principle:
Principle #10Preliminary action

3Reliability

If large volumes are used for sample processing, then sufficient reagents are available for complete reactions, but resource waste increases and efficiency decreases

Engineering Contradiction:
Improvereaction completenessVSAvoidreagent waste
Core Design Contradiction:
ReliabilityVSLoss of substance

Solution Approach 1:

The system applies different properties to different parts of the fluid system by creating discrete volumes with locally optimized reagent concentrations. Each immiscible-fluid-discrete-volume contains precisely the amount of reagents needed for complete reaction, ensuring reliability of reaction completion while eliminating excess reagent waste through localized volume control

Inventive Principle:
Principle #3Local quality

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 reagent consumption, enhances efficiency, and allows for precise manipulation of nucleic acids, facilitating processes like PCR amplification and sequencing in smaller, more controlled volumes, thereby optimizing resource use and reducing procedural time.

Implementation Method 1

discrete volumes of a first fluid in contact with a second fluid wherein the first and second fluids are immiscible with each other

Methodology Applied
Scientific EffectImmiscibility: Emulsion

Data Source

PatentUS11162137B2Apparatus, system, and method using immiscible-fluid-discrete-volumes
Publication Date: 2021.11.02 APPLIED BIOSYSTEMS LLC
  • US11162137B2 patent drawing
  • US11162137B2 patent drawing
  • US11162137B2 patent drawing

AI summary

Various embodiments of the teachings relate to a system or method for sample preparation or analysis in biochemical or molecular biology procedures. The sample preparation can involve small volume processed in discrete portions or segments or slugs, herein referred to as discrete volumes. A molecular biology procedure can be nucleic acid analysis. Nucleic acid analysis can be an integrated DNA amplification/DNA sequencing procedure.