Wafer-Scale Protein Patterning for Cardiomyocyte Models

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Solution Overview

Problem

Current models for studying Hypertrophic Cardiomyopathy (HCM) lack an appropriate human adult cardiomyocyte model that accurately mimics native heart structure and mechanobiology, with existing models such as primary adult cardiomyocytes and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) exhibiting immaturity and heterogeneity, and failing to accurately recapitulate human maladaptive remodeling and responses to pharmaceuticals.

Innovation Solution

A method for protein patterning using photolithography to generate shelf-stable photoresist patterned glass substrates, which are then used to create patterned hydrogels with controlled stiffness and protein patterns, compatible with hiPSC-CMs, to provide a more physiologically relevant microenvironment for cell culture.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If photolithography is performed on individual substrates, then patterning precision is achieved, but manufacturing productivity is low

Engineering Contradiction:
Improvepatterning precisionVSAvoidmanufacturing productivity
Core Design Contradiction:
Manufacturing precisionVSProductivity

Solution Approach 1:

Multiple individual substrate photolithography processes are merged into a single wafer-scale photolithography process. The invention uses a wafer containing multiple substrate positions, allowing simultaneous patterning of all substrates in one batch, thereby maintaining high patterning precision while dramatically improving manufacturing productivity through parallel processing.

Inventive Principle:
Principle #5Merging (Combining)

2Productivity

If wafer-scale photolithography is used, then manufacturing productivity increases, but device complexity increases

Engineering Contradiction:
Improvemanufacturing productivityVSAvoiddevice complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The wafer is segmented into multiple discrete substrate positions, each capable of receiving identical photolithography patterns. This segmentation allows the complex wafer-scale process to be broken down into standardized, repeatable unit operations at each substrate position, making the overall process more manageable and less complex than a fully customized approach.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The wafer structure serves multiple functions: it acts as a support substrate, a positioning template, and a batch processing carrier. The universal wafer design can accommodate different types of substrates and patterns, reducing the need for specialized equipment and procedures for each patterning task, thereby managing complexity while maintaining high productivity.

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

3Stability of the object's composition

If dicing is performed after photolithography, then shelf-stable patterned substrates are produced, but photoresist damage may occur

Engineering Contradiction:
Improveshelf stabilityVSAvoidphotoresist damage
Core Design Contradiction:
Stability of the object's compositionVSObject-affected harmful factors

Solution Approach 1:

The photolithography patterning is performed on the complete wafer before dicing into individual substrates. This preliminary action ensures that the photoresist patterns are fully formed and stabilized on the supportive wafer structure, which provides mechanical strength during the subsequent dicing process, preventing damage that would occur if individual patterned substrates were handled separately.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The wafer structure serves as a protective cushioning support during the dicing process. By maintaining the substrates attached to the rigid wafer during cutting, the system prevents mechanical stress and damage to the fragile photoresist patterns. The wafer absorbs and distributes the mechanical stresses of dicing, protecting the newly formed patterns until the substrates are ready for use.

Inventive Principle:
Principle #11Beforehand cushioning (Prior cushioning)

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 the production of high-quality, patterned hydrogels that promote mature cardiomyocyte phenotypes, enhancing myofibril alignment, contractility, and mechanical output, thereby improving the accuracy of in vitro HCM models.

Implementation Method 1

generating a photoresist pattern on a wafer using photolithography

Methodology Applied
Scientific EffectPhotolithography: Photography

Implementation Method 2

performing lift-off protein patterning on the photoresist patterned wafer chips

Methodology Applied
Scientific EffectLift-off:

Data Source

PatentUS20230158149A1Wafer-Scale Protein Patterning of Hydrogel Devices
Publication Date: 2023.05.25 RGT UNIV OF CALIFORNIA
  • US20230158149A1 patent drawing
  • US20230158149A1 patent drawing
  • US20230158149A1 patent drawing

AI summary

A method for performing protein patterning is provided. In particular, the method comprises generating a photoresist pattern on a wafer using photolithography; dicing the photoresist patterned wafer into wafer chips; and performing lift-off protein patterning on the photoresist patterned wafer chips. This manufacturing technique scales up the photolithography stage of the lift-off fabrication workflow to generate high quantities of shelf-stable photoresist patterned glass substrates, which can be used to incorporate a protein pattern onto the surface of a hydrogel.