Microfluidic Hydrodynamic Shuttling Chip for Extended Single Cell Culture

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Solution Overview

Problem

Existing microfabricated devices for single cell trapping and culture are limited in space, allowing cells to grow and proliferate for only up to 24 hours, and have low efficiency in cell pairing and co-culture applications.

Innovation Solution

A hydrodynamic shuttling chip device with an array of single-cell trapping units, featuring an incoming channel, chamber, trapping channel, and by-pass channel, designed to capture, culture, and proliferate multiple single cells by fluidic connections and surface coatings, allowing cells to be released into chambers for extended growth and interaction.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of moving object

If cells are trapped in a simple microchannel device, then single cell capture is achieved, but the space is limited and cells can only grow for up to 24 hours

Engineering Contradiction:
Improvecell growth durationVSAvoidavailable space for cell growth
Core Design Contradiction:
Duration of action of moving objectVSVolume of moving object

Solution Approach 1:

The device is segmented into multiple functional units (trapping unit, transfer unit, and culture unit) that are spatially separated. The trapping unit captures cells in microchannels, the transfer unit moves selected cells, and the culture unit provides expanded 3D space for long-term growth. This segmentation resolves the contradiction by decoupling the capture function from the growth function, allowing cells to be captured in a compact region and then transferred to a larger volume for extended culture beyond 24 hours.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention transitions from 2D planar culture in microchannels to 3D volumetric culture in the culture unit. The culture unit provides three-dimensional space that allows cells to grow, spread, and proliferate in multiple directions, dramatically increasing the effective growth volume compared to the confined 2D microchannel environment. This dimensional expansion enables sustained cell growth for extended periods.

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

2Adaptability or versatility

If a simple trapping device is used, then device complexity is reduced, but cell pairing efficiency and co-culture capability are limited

Engineering Contradiction:
Improvecell pairing and co-culture capabilityVSAvoiddevice structure complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The device is designed with multi-functional units that can perform different operations. The trapping unit can capture single cells or cell pairs, the transfer unit can selectively transport different cell types, and the culture unit supports various co-culture configurations. This universality enables the device to handle multiple experimental scenarios (single cell culture, cell pairing, co-culture) without requiring separate devices, thereby improving adaptability while managing complexity through functional integration.

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

Solution Approach 2:

The device employs a nested structure where the trapping unit with microchannels is integrated within the larger culture device, and the transfer unit connects these functional zones. The microchannels are nested within the device body, and the culture chambers are positioned to receive cells from the trapping region. This nesting approach allows multiple functional components to coexist in a compact arrangement, enabling complex cell manipulation capabilities without proportionally increasing overall device complexity.

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

The device enhances cell capture and culture efficiency, enabling cells to grow beyond 24 hours, improve cell pairing, and facilitate the co-culture of multiple cell types, with improved space for cell spread and proliferation.

Implementation Method 1

a trapping channel with length L2, width W2, height H2, located between the capture site and the receiving site and being in fluid connection with the incoming channel and the chamber

Methodology Applied
Scientific EffectHydrodynamic flow resistance: Pressure Gradient

Implementation Method 2

a by-pass channel with length L4, width W4, and height H4, located lateral to the incoming channel, chamber and chamber channel and having a first end and a second end opposite to the first end, the first end branching out from the incoming channel immediately prior to the capture site and the second end joining the chamber channel at the posterior end thereof

Methodology Applied
Scientific EffectFluid flow diversion: Pressure Gradient

Implementation Method 3

a chamber with diameter M and depth D, located posterior to the capture site of the incoming channel and having a receiving site spaced apart from the capture site at a distance of g, the chamber having an interior space adapted for more than one single cell to attach, grow, proliferate, and/or migrate

Methodology Applied
Scientific EffectVolume expansion for cell culture:

Data Source

PatentUS10946381B2Microfluidic hydrodynamic shuttling chip device for highthroughput multiple single cells capture
Publication Date: 2021.03.16 NATIONAL HEALTH RESEARCH INSTITUTE
  • US10946381B2 patent drawing
  • US10946381B2 patent drawing
  • US10946381B2 patent drawing

AI summary

A hydrodynamic shuttling chip device comprising an array of single-cell trapping units is disclosed. Each unit comprises: (a) an incoming channel with a cell capture site; (b) a cell culture chamber located posterior to the cell capture site, having a receiving site spaced apart from the cell capture site at a distance of g; (c) a trapping channel located between the cell capture site and the receiving site; (d) a chamber channel located posterior to and in fluidic connection with the cell culture chamber; and (e) a by-pass channel, located lateral to the incoming channel, chamber and chamber channel and having a first end and a second end opposite to the first end, the first end branching out from the incoming channel immediately prior to the cell capture site and the second end joining the chamber channel. A method of capturing single cells of more than one type is also disclosed.