Microfluidic Module Interconnection for Organ-on-Chip Perfusion

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Solution Overview

Problem

Current microfluidic systems for interconnected organs-on-chips face challenges in sterile interconnection, fluid loss, and bubble introduction, with fixed channels preventing organ replacement and scaling issues, and existing fluid-handling robots limiting high-throughput drug delivery and perfusion protocols.

Innovation Solution

The development of an integrated bio-object microfluidics module with a multiport, rotary planar valve system and toggle valves for controlled fluid flow, enabling sterile interconnection, low-volume fluid management, and independent perfusion of each well in a multi-well plate, using a MicroFormulator system for precise drug delivery and removal.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If fixed microfluidic channels are used to connect organs-on-chips, then interconnection is achieved, but organ replacement is prevented and fluid loss occurs

Engineering Contradiction:
Improveinterconnection stabilityVSAvoidorgan replaceability
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The system divides the microfluidic system into separable modules (organs-on-chips) that can be independently handled. Each organ is a discrete unit that can be removed and replaced without affecting the entire system, resolving the contradiction between stable interconnection and organ replaceability.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Tubing serves as an intermediary component between organs-on-chips, enabling flexible connection and disconnection. The tubing allows organs to be replaced while maintaining fluidic connections, and the system includes features to prevent fluid loss during these operations.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Adaptability or versatility

If tubing is used to connect separate organs, then organ replaceability is enabled, but fluid loss and bubble introduction occur

Engineering Contradiction:
Improveorgan replaceabilityVSAvoidfluid loss
Core Design Contradiction:
Adaptability or versatilityVSLoss of substance

Solution Approach 1:

The system performs preliminary actions to prevent fluid loss before disconnection occurs. Features such as pre-positioned clamps, sealed connectors, and controlled valve closure ensure that fluid is contained before the actual disconnection happens, eliminating fluid loss during organ replacement.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The system uses disposable, low-cost components such as sterile connectors and tubing sections that can be easily replaced. These disposable elements prevent contamination and fluid loss by being discarded after single use, ensuring sterile conditions without complex sterilization procedures.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

3Adaptability or versatility

If tubing is used for interconnection, then organ replaceability is achieved, but sterilization difficulty increases

Engineering Contradiction:
Improveorgan replaceabilityVSAvoidsterilization ease
Core Design Contradiction:
Adaptability or versatilityVSEase of manufacture

Solution Approach 1:

The system employs disposable, pre-sterilized connectors and tubing components that eliminate the need for complex sterilization procedures. These single-use elements are manufactured sterile and maintain sterility through their design, making the system easy to manufacture and deploy without extensive sterilization infrastructure.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The connectors are designed with self-sealing or self-locking features that maintain sterile barriers without external intervention. The system automatically maintains sterility through its design features, reducing the need for manual sterilization processes.

Inventive Principle:
Principle #25Self-service

4Extent of automation

If centralized fluid-handling robots are used, then fluid delivery is achieved, but high-throughput perfusion protocols are limited

Engineering Contradiction:
Improvefluid delivery automationVSAvoidhigh-throughput perfusion capability
Core Design Contradiction:
Extent of automationVSProductivity

Solution Approach 1:

The system divides fluid handling into distributed, independent units at each organ module rather than using a single centralized robot. Each module can be perfused independently and simultaneously, enabling high-throughput protocols while maintaining automation through localized fluid handling mechanisms.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The system uses universal, standardized connectors and interfaces that allow the same fluid handling approach to be applied across multiple organs simultaneously. This multi-functional design enables parallel processing of multiple samples, dramatically increasing throughput compared to sequential centralized handling.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Data Source

PatentUS10577574B2Interconnections of multiple perfused engineered tissue constructs and microbioreactors, multi-microformulators and applications of the same
Publication Date: 2020.03.03 VANDERBILT UNIV
  • US10577574B2 patent drawing
  • US10577574B2 patent drawing
  • US10577574B2 patent drawing

AI summary

The invention relates to a system of fluidic valves and pumps and associated fluidic channels integratable into a bio-object microfluidics module. The module includes input and output buses; upstream and downstream interconnection bus control valves (CVs) coupled to the input and output buses, respectively. It may include arterial, venous, wash and waste bus lines, each connecting between the upstream and downstream interconnection bus CVs. It may also include an input CV connecting to the arterial bus line, upstream interconnection bus CV, bio-object and inlets, and an output CV connecting to the bio-object, input CV, downstream interconnection bus CV and outlets; and a pump connecting between the input CV and bio-object. The system of fluidic valves and pumps can be arranged to provide MicroFormulator functionality enabling precise mixtures of drugs, chemicals, or biochemicals to be delivered in a time-dependent fashion to biological entities housed in individual wells or chambers.