Droplet Actuator Concentration Normalization via Segmentation

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Solution Overview

Problem

Droplet actuators face challenges in managing and processing droplets with varying concentrations of substances-of-interest, particularly in mixing and processing droplets for biological or chemical analysis, such as nucleic acid sequencing, where uniform concentrations are required for accurate results.

Innovation Solution

A method and system utilizing a droplet actuator with electrodes to generate discrete dilution droplets from input droplets, allowing for the adjustment of concentrations to achieve a target concentration by combining specific dilution droplets, enabling the normalization of concentrations within a droplet set for subsequent analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If droplets with varying concentrations are processed directly, then processing speed is maintained, but analysis accuracy deteriorates due to non-uniform concentrations

Engineering Contradiction:

Improveanalysis accuracyVSAvoidprocessing speed

Core Design Contradiction:

Measurement precisionVSProductivity

Solution Approach 1:

The input droplet is segmented into multiple discrete dilution droplets, each containing a specific concentration of the substance-of-interest. This segmentation allows selective combination of droplets to achieve the target concentration while maintaining processing efficiency.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

Dilution droplets are generated in advance with predetermined concentrations before the final combination step. This preliminary preparation enables rapid assembly of the target concentration without time-consuming adjustments during analysis.

Inventive Principle:

Principle #10Preliminary action

2Stability of the object's composition

If dilution droplets are generated and combined to achieve target concentration, then concentration uniformity is improved, but device complexity increases

Engineering Contradiction:

Improveconcentration uniformityVSAvoiddroplet operation complexity

Core Design Contradiction:

Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The droplet actuator performs multiple functions including droplet generation, dilution, mixing, and concentration adjustment using a single integrated platform with electrodes, reducing the need for multiple separate devices.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The system adjusts droplet concentration by changing the number and volume of dilution droplets combined, rather than physically modifying the droplet composition. This parameter-based approach simplifies the device architecture.

Inventive Principle:

Principle #35Parameter changes

3Manufacturing precision

If discrete dilution droplets are generated from input droplet, then concentration precision is improved, but time consumption increases

Engineering Contradiction:

Improveconcentration precisionVSAvoidtime consumption

Core Design Contradiction:

Manufacturing precisionVSLoss of time

Solution Approach 1:

The system uses periodic electrode activation to generate and manipulate dilution droplets in a rhythmic sequence, enabling precise concentration control through timed droplet generation and combination operations.

Inventive Principle:

Principle #19Periodic action

Solution Approach 2:

The system creates multiple copies of the input droplet at different dilution levels, then combines appropriate copies to achieve the target concentration. This copying approach enables precise concentration control without repeated manual manipulation.

Inventive Principle:

Principle #26Copying

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 the efficient normalization of droplet concentrations, facilitating simultaneous processing and analysis of multiple samples with varying initial concentrations, improving the accuracy and efficiency of techniques like DNA sequencing by ensuring uniform genetic material concentrations.

Implementation Method 1

A droplet actuator typically includes one or more substrates configured to form a surface or gap for conducting droplet operations. The one or more substrates establish a droplet operations surface or gap for conducting droplet operations and may also include electrodes arranged to conduct the droplet operations.

Methodology Applied

Scientific EffectElectrowetting: Electrowetting

Data Source

PatentUS10450598B2Systems and methods for obtaining a droplet having a designated concentration of a substance-of-interest

Publication Date: 2019.10.22 ILLUMINA INC

AI summary

Method includes providing a droplet actuator having a droplet-operations gap and a plurality of electrodes positioned along the droplet-operations gap. The method also includes positioning an input droplet in the droplet-operations gap. The input droplet has a starting concentration of a substance-of-interest. The method also includes conducting droplet operations within the droplet-operations gap using the electrodes to generate discrete dilution droplets that are formed from the input droplet. The dilution droplets and a remainder of the input droplet form a droplet set. At least two of the dilution droplets in the droplet set having different concentrations of the substance-of-interest. The method also includes combining a select number of the droplets from the droplet set to form an output droplet having a modified concentration that is substantially equal to a designated target concentration.