Droplet Actuator Reagent Reconstitution and Plasma Separation

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Solution Overview

Problem

Current digital microfluidics techniques face challenges in achieving accurate and precise analysis, particularly in assays involving droplet actuation, due to issues such as reagent reconstitution, hemoglobin measurement, and plasma separation from whole blood, which require improved methods for accuracy and precision.

Innovation Solution

The method involves reconstituting dried reagents using a buffer, measuring dye or tracer components to assess reconstitution, and employing droplet actuation techniques for precise handling and separation of plasma from whole blood, including the use of agglutination reagents and electrowetting for efficient droplet manipulation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If automated droplet actuation techniques are used for assay processing, then productivity is improved, but measurement precision deteriorates due to variability in droplet manipulation and reagent reconstitution

Engineering Contradiction:
Improveassay processing throughputVSAvoidanalyte measurement accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The system measures the dye or tracer in the reconstituted reagent droplet to determine the extent of reconstitution, then uses this information to adjust or correct subsequent assay measurements. This feedback loop compensates for variability introduced by automated droplet manipulation, maintaining measurement precision while enabling high-throughput processing.

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The invention changes the physical state of reagents from dried to reconstituted form, and uses measurable parameters (dye/tracer concentration) to monitor and control the reconstitution process. This allows the system to adapt to variations in droplet volume and mixing efficiency, ensuring consistent assay results across high-throughput processing.

Inventive Principle:
Principle #35Parameter changes

2Ease of manufacture

If reagents are dried on the droplet actuator surface, then device complexity is reduced and ease of manufacture is improved, but reliability deteriorates due to potential reconstitution issues

Engineering Contradiction:
Improvecartridge assembly simplicityVSAvoidreagent reconstitution consistency
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

Reagents are dried onto the droplet actuator surface in advance during cartridge manufacturing, preparing them for later reconstitution during assay operation. This preliminary action simplifies cartridge assembly and storage, while the subsequent measurement and correction steps ensure reliable and consistent reconstitution performance.

Inventive Principle:
Principle #10Preliminary action

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 enhances the accuracy and precision of assays by ensuring proper reagent reconstitution and effective plasma separation, enabling reliable measurements of hemoglobin and other analytes in whole blood samples.

Implementation Method 1

measuring the dye or tracer in the reconstituted reagent droplet to produce a dye or tracer measurement

Methodology Applied
Scientific EffectAbsorbance spectroscopy: Absorption Spectroscopy

Implementation Method 2

the dye or tracer may include a fluorophore

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 3

employing droplet actuation techniques for precise handling and separation of plasma from whole blood, including the use of agglutination reagents and electrowetting for efficient droplet manipulation

Methodology Applied
Scientific EffectElectrowetting: Electrowetting

Implementation Method 4

combining the sample droplet with an agglutination reagent droplet to provide a combined agglutination droplet including a plasma fraction and a red blood cell fraction

Methodology Applied
Scientific EffectAgglutination: Coagulation

Data Source

PatentUS20230194540A1Digital microfluidics analytical techniques
Publication Date: 2023.06.22 BAEBIES INC
  • US20230194540A1 patent drawing
  • US20230194540A1 patent drawing
  • US20230194540A1 patent drawing

AI summary

Systems and methods for measuring hemoglobin, G6PD activity, and or bilirubin activity in a sample, including measuring the absorbance of a sample, removing background interfering signals, and quantifying the relevant analyte. Systems and methods for reconstituting a reagent in a droplet actuator. Systems and methods for separating plasma from a whole blood sample on a droplet actuator, including combining a sample droplet with an agglutination reagent droplet and using a novel combination of droplet operations to split the sample into a plasma and an agglutinated red blood cell fraction.