Design, simulation, and fabrication of three-dimensional microsystem components using grayscale photolithography

Smith, Melissa; Berry, Shaun; Parameswaran, Lalitha; Holtsberg, Christopher; Siegel, Noah; Lockwood, Ronald B.; Chrisp, Michael P.; Freeman, Darren; Rothschild, M.

doi:10.1117/1.jmm.18.4.043507

Cited by 30 publications

(19 citation statements)

References 32 publications

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“…41 Photolithography using grayscale masks also enables to fabricate 3D microfluidics in one step. 42 However, these masks are generally very costly to fabricate. Lai et al employed backside diffused light lithography using pseudo-grayscale masks as a cost-effective and simple approach to fabricate 3D microfluidic in a single UV step.…”

Section: Fabricationmentioning

confidence: 99%

Conventional and emerging strategies for the fabrication and functionalization of PDMS-based microfluidic devices

2021

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Section: Fabricationmentioning

confidence: 99%

Conventional and emerging strategies for the fabrication and functionalization of PDMS-based microfluidic devices

2021

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“…To test the impact of prestress in 3D tissues on electrophysiology maturation, we sought to create micro heart muscle arrays (µHM) of various geometries, as simple continuum mechanics models of tissue compaction predict a direct link between tissue geometry and prestress [8]. Soft lithography is a common technique for creating molds to control the geometry of micro-scale engineered tissues, but is time consuming, requires specialized facilities, and limits the complexity of devices produced [12], [13]. Due to these inherent limitations, we turned to high resolution 3D-printing for mold creation.…”

Section: Mainmentioning

confidence: 99%

Chronic Prestress Regulation of Micro-Heart Muscle Physiology

Simmons

Shuftan

Guo

et al. 2022

Preprint

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Tissue engineered in-vitro models are an essential tool in biomedical research. Tissue geometry is a key determinant of function, but controlling geometry of micro-scale tissues remains a challenge. We developed a new double molding approach that allows precise replication of high-resolution stereolithographic prints into poly(dimethylsiloxane), facilitating rapid design iterations and highly parallelized sample production. Hydrogels are used as an intermediary mold, and gel mechanical properties including crosslink density predict replication fidelity. We leveraged this approach to study the effects of geometry on the electrophysiology of miniaturized heart muscles engineered from human induced pluripotent stem cells (iPSC). Geometries predicted to increase tissue prestress globally affected cardiomyocyte structure and tissue electrophysiology. Strikingly, pharmacologic studies revealed a prestress threshold is required for sodium channel function. Analysis of RNA and protein levels suggest electrophysiology changes were related to post-transcriptional and potentially post-translational changes of the gap-junction protein Connexin 43 and the sodium channel Nav1.5.

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“…Photolithography is a common technique for creating molds to control the geometry of these microscale engineered tissues, but it is time consuming, requires specialized facilities, and limits the complexity of devices produced. , Due to these inherent limitations, stereolithographic (SLA) 3D printing has been suggested as a replacement for soft lithography to enable rapid fabrication of microdevices. With the invention of new, higher-resolution printers capable of resolutions under 25 μm in all x – y – z directions, this would enable tissue creation at sizes that are both biologically relevant and practical .…”

Section: Introductionmentioning

confidence: 99%

Hydrogel-Assisted Double Molding Enables Rapid Replication of Stereolithographic 3D Prints for Engineered Tissue Design

Simmons

Schuftan

Ramahdita

et al. 2023

ACS Appl. Mater. Interfaces

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Tissue-engineered in vitro models are an essential tool in biomedical research. Tissue geometry is a key determinant of function, but controlling the geometry of microscale tissues remains challenging. Additive manufacturing approaches have emerged as a promising means for rapid and iterative changes in the geometry of microdevices. However, it has been shown that poly(dimethylsiloxane) (PDMS) cross-linking is often inhibited at the interface of materials printed with stereolithography. While approaches to replica mold stereolithographic three-dimensional (3D) prints have been described, these methods are inconsistent and often lead to print destruction when unsuccessful. Additionally, 3D-printed materials often leach toxic chemicals into directly molded PDMS. Here, we developed a double molding approach that allows precise replication of high-resolution stereolithographic prints into poly(dimethylsiloxane) (PDMS) elastomer, facilitating rapid design iterations and highly parallelized sample production. Inspired by lost wax casting, we used hydrogels as intermediary molds to transfer high-resolution features from high-resolution 3D prints into PDMS, while previously published work focused on enabling direct molding of PDMS onto 3D prints through the use of coatings and post-crosslinking treatments of the 3D print itself. Hydrogel mechanical properties, including cross-link density, predict replication fidelity. We demonstrate the ability of this approach to replicate a variety of shapes that would be impossible to create using photolithography techniques traditionally used to create engineered tissue designs. This method also enabled the replication of 3D-printed features into PDMS that would not be possible with direct molding as the stiffness of these materials leads to material fracture when unmolding, while the increased toughness in the hydrogels can elastically deform around complex features and maintain replication fidelity. Finally, we highlight the ability of this method to minimize the potential for toxic materials to transfer from the original 3D print into the PDMS replica, enhancing its use for biological applications. This minimization of the transfer of toxic materials has not been reported in other previously reported methods describing replication of 3D prints into PDMS, and we demonstrate its use through the creation of stem cell-derived microheart muscles. This method can also be used in future studies to understand the effects of geometry on engineered tissues and their constitutive cells.

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Design, simulation, and fabrication of three-dimensional microsystem components using grayscale photolithography

Cited by 30 publications

References 32 publications

Conventional and emerging strategies for the fabrication and functionalization of PDMS-based microfluidic devices

Conventional and emerging strategies for the fabrication and functionalization of PDMS-based microfluidic devices

Chronic Prestress Regulation of Micro-Heart Muscle Physiology

Hydrogel-Assisted Double Molding Enables Rapid Replication of Stereolithographic 3D Prints for Engineered Tissue Design

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