Microfluidic Isolation Pen with Diffusive Connection Region

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Solution Overview

Problem

Microfluidic devices face challenges in effectively isolating and analyzing biological micro-objects while maintaining the integrity of the fluidic media, as existing technologies struggle to prevent the flow of media between different regions, leading to contamination and inefficient diffusion-based communication.

Innovation Solution

A microfluidic device with a flow region and a microfluidic sequestration pen, featuring an isolation structure and a connection region that allows diffusion between fluidic media while preventing bulk flow, enabling the isolation of biological micro-objects and the production of analytes without contamination.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a physical barrier is used to isolate fluidic regions, then bulk flow between regions is prevented, but diffusion-based communication between regions is blocked

Engineering Contradiction:
Improveisolation integrityVSAvoiddiffusion communication
Core Design Contradiction:
ReliabilityVSLoss of substance

Solution Approach 1:

The patent introduces a semi-permeable membrane as an intermediary structure between the flow region and isolation region. This membrane selectively permits diffusion of analytes while preventing bulk flow, thus mediating between the conflicting requirements of isolation integrity and diffusion communication

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The isolation structure incorporates porous materials that allow selective passage of molecules based on size and concentration gradients. The porous structure enables analyte diffusion from the isolation region to the flow region while maintaining physical isolation to prevent bulk fluid mixing

Inventive Principle:
Principle #31Porous materials

2Reliability

If the connection region is made longer to improve isolation, then bulk flow prevention is enhanced, but diffusion efficiency is reduced

Engineering Contradiction:
Improveflow isolationVSAvoiddiffusion time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The connection region is designed with spatially varying properties: it has a larger cross-sectional area near the isolation region to facilitate diffusion, and tapers toward the flow region to maintain isolation. This local quality variation optimizes both diffusion efficiency and flow prevention

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The connection region utilizes a three-dimensional tapered geometry rather than a simple linear extension. By varying the cross-sectional area along its length, the design creates multiple diffusion pathways while maintaining sufficient length for flow isolation, effectively using dimensional variation to resolve the contradiction

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

3Quantity of substance

If the isolation region volume is increased to accommodate more biological micro-objects, then isolation capacity is improved, but analyte diffusion rate to the flow region is reduced

Engineering Contradiction:
Improveisolation capacityVSAvoiddiffusion rate
Core Design Contradiction:
Quantity of substanceVSSpeed

Solution Approach 1:

The isolation region is segmented into multiple smaller compartments or chambers, each containing a subset of biological micro-objects. This segmentation increases the surface-area-to-volume ratio, providing more diffusion interfaces while maintaining adequate isolation capacity for the total number of micro-objects

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The design employs a hierarchical structure where multiple isolation regions are nested within or adjacent to each other, creating a cascading diffusion pathway. Analytes can diffuse through multiple smaller regions in sequence, which collectively provide large isolation capacity while maintaining efficient overall diffusion to the flow region

Inventive Principle:
Principle #7Nested doll (Nesting)

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 configuration allows for the efficient isolation and analysis of biological micro-objects, preventing contamination and ensuring that analytes can diffuse into the flow region for detection, thereby enhancing the accuracy and reliability of microfluidic processes.

Implementation Method 1

components of the second medium are able to diffuse into the first medium or components of the first medium are able to diffuse into the second medium

Methodology Applied
Scientific EffectDiffusion: Diffusion

Data Source

PatentUS20230347347A1Microfluidic devices having isolation pens and methods of testing biological micro-objects with same
Publication Date: 2023.11.02 BRUKER SPATIAL BIOLOGY INC
  • US20230347347A1 patent drawing
  • US20230347347A1 patent drawing
  • US20230347347A1 patent drawing

AI summary

A microfluidic device can comprise at least one swept region that is fluidically connected to unswept regions. The fluidic connections between the swept region and the unswept regions can enable diffusion but substantially no flow of media between the swept region and the unswept regions. The capability of biological micro-objects to produce an analyte of interest can be assayed in such a microfluidic device. Biological micro-objects in sample material loaded into a microfluidic device can be selected for particular characteristics and disposed into unswept regions. The sample material can then be flowed out of the swept region and an assay material flowed into the swept region. Flows of medium in the swept region do not substantially affect the biological micro-objects in the unswept regions, but any analyte of interest produced by a biological micro-object can diffuse from an unswept region into the swept region, where the analyte can react with the assay material to produce a localized detectable reaction. Any such detected reactions can be analyzed to determine which, if any, of the biological micro-objects are producers of the analyte of interest.