Gravity Sedimentation Droplet Separation on Patterned Support

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Solution Overview

Problem

Current methods for separating components from biological samples, such as blood, often result in significant losses due to lengthy manipulations and over-processing, especially when dealing with small sample volumes, and lack efficiency in isolating enriched samples with minimal material usage.

Innovation Solution

The method involves subjecting a biological sample droplet to a gravitational force to separate components of different densities into distinct regions, followed by applying an electric field to divide the droplet into product droplets, and optionally washing and re-separating these droplets to enhance component enrichment and minimize losses.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If traditional centrifugation and multiple separation manipulations are used to separate biological components, then separation selectivity and purity can be improved, but processing time increases and component loss increases

Engineering Contradiction:
Improveseparation purityVSAvoidprocessing time
Core Design Contradiction:
Manufacturing precisionVSLoss of time

Solution Approach 1:

The support surface is divided into multiple discrete regions, each capable of receiving and retaining separated biological components. This segmentation allows simultaneous processing of multiple components in parallel, reducing total processing time while maintaining separation purity through dedicated regions for each component type.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The support surface is pre-patterned with discrete regions before sample application. This preliminary structuring guides the separation process and enables components to be directed to predetermined locations, eliminating the need for subsequent manual sorting steps and reducing overall processing time.

Inventive Principle:
Principle #10Preliminary action

2Manufacturing precision

If multiple iterations of separation and washing are performed to enhance component enrichment, then component concentration and purity improve, but component viability decreases due to over-processing

Engineering Contradiction:
Improvecomponent enrichmentVSAvoidcomponent viability
Core Design Contradiction:
Manufacturing precisionVSReliability

Solution Approach 1:

By dividing the support into discrete regions, the system achieves high component enrichment through spatial separation in a single pass, eliminating the need for multiple iterative washing steps. This segmentation approach provides sufficient separation purity and concentration without subjecting components to repeated processing that would compromise viability.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention extracts and isolates specific biological components directly to dedicated regions on the support surface, achieving enrichment without requiring multiple washing iterations. This direct extraction approach minimizes the number of times components are handled and exposed to potentially harmful processing conditions.

Inventive Principle:
Principle #2Taking out (Extraction)

3Quantity of substance

If large volumes of biological fluid are used to compensate for processing losses, then sufficient material can be obtained for analysis, but the cost and complexity of processing increases

Engineering Contradiction:
Improvebiological material availabilityVSAvoidprocessing complexity
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

The support surface with its pre-patterned discrete regions performs the separation and concentration functions automatically as the biological sample flows across it. This self-service mechanism eliminates the need for complex external processing equipment and multiple manual steps, reducing overall processing complexity while working effectively with small sample volumes.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The invention changes the physical parameters of the support surface (surface properties, region geometry, material composition) to optimize separation efficiency. By adjusting these parameters, the system achieves high recovery rates with minimal sample material, eliminating the need to process large volumes that would increase complexity and cost.

Inventive Principle:
Principle #35Parameter changes

4Loss of substance

If conventional separation methods are used with small sample volumes, then material savings are achieved, but separation efficiency and selectivity decrease

Engineering Contradiction:
Improvematerial usageVSAvoidseparation efficiency
Core Design Contradiction:
Loss of substanceVSProductivity

Solution Approach 1:

The discrete region segmentation on the support surface enables efficient separation of small sample volumes by providing dedicated capture zones for each component type. This segmentation prevents cross-contamination and ensures that even trace amounts of biological material are effectively separated and concentrated, maintaining high separation efficiency with minimal material usage.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention replaces complex mechanical separation systems (centrifuges, filters, multiple pipetting steps) with a passive separation mechanism based on the support surface geometry and surface properties. This substitution achieves high separation efficiency with small volumes without requiring energy-intensive or complex mechanical operations.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

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 effectively increases component concentration by up to 10-fold in specific regions, reduces processing losses, and allows for efficient separation of components like red and white blood cells from plasma with minimal sample material, preserving viability and purity.

Implementation Method 1

subjecting the biological sample droplet to a gravitational force to produce two or more regions in the biological sample droplet on the support surface, where each region in the biological sample droplet includes a component from the biological sample droplet having a different density

Methodology Applied
Scientific EffectGravity sedimentation: Sedimentation

Implementation Method 2

conveying one or more product droplets along the support surface by applying an electric field to discrete regions of the support

Methodology Applied
Scientific EffectElectric field force: Electric Field

Data Source

PatentUS10059922B2Methods and systems for separating components of a biological sample with gravity sedimentation
Publication Date: 2018.08.28 BECTON DICKINSON & CO
  • US10059922B2 patent drawing
  • US10059922B2 patent drawing
  • US10059922B2 patent drawing

AI summary

Aspects of the present disclosure include methods for separating components having different densities from a biological sample droplet. Methods according to certain embodiments include contacting a surface of a support with a biological sample droplet that includes components of different densities; subjecting the biological sample droplet to a gravitational force to produce two or more regions in the biological sample droplet on the support surface, where each region in the biological sample droplet includes a component from the biological sample droplet having a different density; separating the biological sample droplet into two or more product droplets, wherein each product droplet includes a different region of the biological sample droplet; and collecting the one or more product droplets. Systems for practicing the subject methods are also described. Computer systems and kits are also provided.