Microfluidic electrocage device for live-cell CT imaging

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Solution Overview

Problem

Conventional methods for fabricating microfluidic devices are challenging due to difficulties in rotating particles at a slow enough rate for low light-level data acquisition in computed tomography imaging, and existing cell media do not adequately support cell life while allowing for slow rotation rates.

Innovation Solution

The diffusive bonding layer method simplifies fabrication by allowing for precise design and bonding without high pressure/temperature requirements, and a high viscosity cell medium is used, comprising long-chain polysaccharides like Ficoll® and dextran, to slow cell rotation and enhance stability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Strength

If conventional high pressure/temperature bonding methods are used to fabricate microfluidic devices, then bonding strength is achieved, but fabrication complexity and cost increase, and large voids are formed in the bonded area

Engineering Contradiction:
Improvebonding strengthVSAvoidfabrication complexity
Core Design Contradiction:
StrengthVSDevice complexity

Solution Approach 1:

The patent changes the bonding parameters from high pressure and temperature to room temperature and atmospheric pressure conditions. The diffusive bonding layer technique uses a photosensitive resin that cures at room temperature, eliminating the need for high pressure/temperature equipment and simplifying the fabrication process while maintaining bonding strength

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces a diffusive bonding layer as an intermediary material between the microfluidic device components. This photosensitive resin layer facilitates bonding under mild conditions and prevents the formation of large voids that occur in conventional direct bonding methods, thereby reducing fabrication complexity while maintaining bond strength

Inventive Principle:
Principle #24Intermediary (Mediator)

2Manufacturing precision

If conventional bonding methods are used, then bonding is achieved, but alignment precision is reduced due to formation of large voids

Engineering Contradiction:
Improvealignment precisionVSAvoidbonding quality
Core Design Contradiction:
Manufacturing precisionVSStrength

Solution Approach 1:

The diffusive bonding layer acts as an intermediary that fills gaps and conforms to surface abnormalities, preventing the formation of large voids. This photosensitive resin layer ensures uniform contact between bonding surfaces, thereby improving alignment precision and bonding quality simultaneously

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The bonding layer is applied locally to conform to the specific surface topology of each component. The photosensitive resin diffuses and adapts to local surface variations, ensuring precise alignment and void-free bonding in each local area rather than requiring uniform bonding across the entire surface

Inventive Principle:
Principle #3Local quality

3Strength

If high pressure/temperature bonding is used, then bonding strength is achieved, but temperature sensitive materials and delicate microfeatures are damaged

Engineering Contradiction:
Improvebonding strengthVSAvoidthermal damage to materials
Core Design Contradiction:
StrengthVSObject-affected harmful factors

Solution Approach 1:

The patent fundamentally changes the bonding parameters from high temperature and pressure to room temperature and atmospheric pressure. The photosensitive resin-based diffusive bonding layer cures through UV exposure or chemical reaction at mild conditions, eliminating thermal damage to temperature-sensitive materials and delicate microfeatures while maintaining adequate bonding strength

Inventive Principle:
Principle #35Parameter changes

4Reliability

If conventional cell media are used, then cell life is supported, but cell rotation rate cannot be slowed enough for low light-level imaging

Engineering Contradiction:
Improvecell viabilityVSAvoidcell rotation rate
Core Design Contradiction:
ReliabilityVSSpeed

Solution Approach 1:

The patent creates a composite cell medium by combining conventional cell culture medium with high viscosity additives such as Ficoll or dextran. This composite medium maintains the biochemical properties necessary for cell viability while the high viscosity component slows down cell rotation to rates suitable for low light-level CT imaging

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent changes the physical parameter of viscosity in the cell medium by adding high molecular weight polymers. This increases the medium's viscosity to slow cell rotation while the biochemical composition is maintained to support cell life, thereby resolving the contradiction between cell viability and rotation rate control

Inventive Principle:
Principle #35Parameter changes

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 enables more robust and cost-effective microfluidic device fabrication, allowing for slower and more stable cell rotation, improving reconstruction quality and reducing distortion in computed tomography imaging.

Implementation Method 1

diffusive bonding layer method set forth in this application permits simpler design, fabrication, and bonding procedures as compared to traditional high pressure/temperature bonding

Methodology Applied
Scientific EffectDiffusion: Diffusion

Implementation Method 2

impinging UV light on portions of the positive photoresist layer of each of the first wafer and the second wafer to pattern the positive photoresist layer and expose regions of the at least one metal layer

Methodology Applied
Scientific EffectPhotopolymerisation: Photopolymerisation

Implementation Method 3

An array of microelectrodes rotates particles by application of dielectrophoretic forces

Methodology Applied
Scientific EffectDielectrophoresis: Diffusiophoresis

Implementation Method 4

a high viscosity cell medium is used, comprising long-chain polysaccharides like Ficoll® and dextran, to slow cell rotation and enhance stability

Methodology Applied
Scientific EffectViscosity:

Data Source

PatentUS10391485B2Microfluidic electrocage device and cell medium for trapping and rotating cells for live-cell computed tomography (CT)
Publication Date: 2019.08.27 THE ARIZONA BOARD OF REGENTS ON BEHALF OF THE UNIV OF ARIZONA
  • US10391485B2 patent drawing
  • US10391485B2 patent drawing
  • US10391485B2 patent drawing

AI summary

A microfluidic device useable for performing live cell computed tomography imaging is fabricated with a cover portion including a first wafer with at least one metal patterned thereon, a base portion including a second wafer with at least one metal patterned thereon and negative photoresist defining recesses therein, and a diffusive bonding layer including a negative photoresist arranged to join the cover portion and the base portion. A composition useful in live cell computer topography includes a long-chain polysaccharide at a concentration of from about 0.01% to about 10.0% in cell culture medium for supporting cell life while enabling cell rotation rate to be slowed to a speed commensurate with low light level imaging.