Leaf-inspired microcontact printing vascular patterns.

The vascularization of tissue grafts is critical for maintaining viability of the cells within a transplanted graft. A number of strategies are currently being investigated including very promising microfluidics systems. Here, we explored the potential for generating a vasculature-patterned endothelial cells that could be integrated into distinct layers between sheets of primary cells. Bioinspired from the leaf veins, we generated a reverse mold with a fractal vascular-branching pattern that models the unique spatial arrangement over multiple length scales that precisely mimic branching vasculature. By coating the reverse mold with 50 μg ml-1 of fibronectin and stamping enabled selective adhesion of the human umbilical vein endothelial cells (HUVECs) to the patterned adhesive matrix, we show that a vascular-branching pattern can be transferred by microcontact printing. Moreover, this pattern can be maintained and transferred to a 3D hydrogel matrix and remains stable for up to 4 d. After 4 d, HUVECs can be observed migrating and sprouting into Matrigel. These printed vascular branching patterns, especially after transfer to 3D hydrogels, provide a viable alternative strategy to the prevascularization of complex tissues

Shape Memory Polymer Micromachining for Wearable Sensors and Health Monitoring

Despite many advances in mobile communications and data science remote, continuous health monitoring remains a challenge due to a dearth of appropriate wearable sensors. These sensors must bend and stretch along with the human body while maintaining consistent performance. As most standard electronics component are made of rigid, brittle materials, there is an inherent mechanical mismatch that limits the usefulness of current sensor technology for wearable health monitoring. This work introduces pre-stressed thermoplastic shape memory polymers as a fabrication tool to produce complex, hierarchically wrinkled thin films for use as wearable sensing electrodes and wearable strain sensors. Additionally, a series of scalable, polymer compatible micromachining techniques are discussed for fabricating these sensors.Hierarchical wrinkled structures significantly enhance the surface area (>600%) as compared to planar thin films. Integrated with a flexible polymer carrier, wrinkled electrodes can provide increased efficiency with low sample volumes for electrochemical sensing on human skin. This enables potential application of bioanalyte detection in human sweat.Out of plane wrinkling in thin films can also serve as a strain relief. By transferring wrinkled metal thin films into an elastic carrier, highly elastic strain sensors can be fabricated and used to detect and monitor human motion. These sensors show very high gauge factors (as high as 42) over a wide dynamic range (>150%). Worn on the chest, these sensors can monitor breath rate and approximate lung volume based on chest wall displacement as is demonstrated in this work.Finally, future work with possibility of incorporating a water soluble sacrificial layer are discussed. The addition of hydrophilic polymers as a lift off layer increases flexibility and ease of transferring wrinkled thin films. Importantly water-based processing would convert the current solvent-base lift off process to a more green manufacturing process

Flexible shrink-induced high surface area electrodes for electrochemiluminescent sensing

Photolithographically defined metallic thin film on commodity shrink-wrap is leveraged to create robust electrodes. By thermally shrinking the film, electrodes are reduced by 20x in footprint for improved resolution and conductivity with >600% enhancements in electrochemically active surface area; as electrochemiluminescent sensors, they demonstrate improved limits of detection

Highly stretchable wrinkled gold thin film wires.

With the growing prominence of wearable electronic technology, there is a need to improve the mechanical reliability of electronics for more demanding applications. Conductive wires represent a vital component present in all electronics. Unlike traditional planar and rigid electronics, these new wearable electrical components must conform to curvilinear surfaces, stretch with the body, and remain unobtrusive and low profile. In this paper, the piezoresistive response of shrink induced wrinkled gold thin films under strain demonstrates robust conductive performance in excess of 200% strain. Importantly, the wrinkled metallic thin films displayed negligible change in resistance of up to 100% strain. The wrinkled metallic wires exhibited consistent performance after repetitive strain. Importantly, these wrinkled thin films are inexpensive to fabricate and are compatible with roll to roll manufacturing processes. We propose that these wrinkled metal thin film wires are an attractive alternative to conventional wires for wearable applications

Leaf-inspired microcontact printing vascular patterns.

The vascularization of tissue grafts is critical for maintaining viability of the cells within a transplanted graft. A number of strategies are currently being investigated including very promising microfluidics systems. Here, we explored the potential for generating a vasculature-patterned endothelial cells that could be integrated into distinct layers between sheets of primary cells. Bioinspired from the leaf veins, we generated a reverse mold with a fractal vascular-branching pattern that models the unique spatial arrangement over multiple length scales that precisely mimic branching vasculature. By coating the reverse mold with 50 μg ml-1 of fibronectin and stamping enabled selective adhesion of the human umbilical vein endothelial cells (HUVECs) to the patterned adhesive matrix, we show that a vascular-branching pattern can be transferred by microcontact printing. Moreover, this pattern can be maintained and transferred to a 3D hydrogel matrix and remains stable for up to 4 d. After 4 d, HUVECs can be observed migrating and sprouting into Matrigel. These printed vascular branching patterns, especially after transfer to 3D hydrogels, provide a viable alternative strategy to the prevascularization of complex tissues

Protein footprinting by pyrite shrink-wrap laminate

The structure of macromolecules and their complexes dictate their biological function. In "footprinting", the solvent accessibility of the residues that constitute proteins, DNA and RNA can be determined from their reactivity to an exogenous reagent such as the hydroxyl radical (·OH). While ·OH generation for protein footprinting is achieved by radiolysis, photolysis and electrochemistry, we present a simpler solution. A thin film of pyrite (cubic FeS2) nanocrystals deposited onto a shape memory polymer (commodity shrink-wrap film) generates sufficient ·OH via Fenton chemistry for oxidative footprinting analysis of proteins. We demonstrate that varying either time or H2O2 concentration yields the required ·OH dose-oxidation response relationship. A simple and scalable sample handling protocol is enabled by thermoforming the "pyrite shrink-wrap laminate" into a standard microtiter plate format. The low cost and malleability of the laminate facilitates its integration into high throughput screening and microfluidic devices

Shrinky-Dink Hanging Drops: A Simple Way to Form and Culture Embryoid Bodies

Embryoid bodies (EB) are aggregates of embryonic stem cells. The most common way of creating these aggregates is the hanging drop method, a laborious approach of pipetting an arbitrary number of cells into well plates. The interactions between the stem cells forced into close proximity of one another promotes the generation of the EBs. Because the media in each of the wells has to be manually exchanged every day, this approach is manually intensive

Tunable shrink-induced honeycomb microwell arrays for uniform embryoid bodies.

Embryoid body (EB) formation closely recapitulates early embryonic development with respect to lineage commitment. Because it is greatly affected by cell-cell and cell-substrate interactions, the ability to control the initial number of cells in the aggregates and to provide an appropriate substrate are crucial parameters for uniform EB formation. Here we report of an ultra-rapid fabrication and culture method utilizing a laser-jet printer to generate closely arrayed honeycomb microwells of tunable sizes for the induction of uniform EBs from single cell suspension. By printing various microwell patterns onto pre-stressed polystyrene sheets, and through heat induced shrinking, high aspect micromolds are generated. Notably, we achieve rounded bottom polydimethylsiloxane (PDMS) wells not easily achievable with standard microfabrication methods, but critical to achieve spherical EBs. Furthermore, by simply controlling the size of the microwells and the concentration of the cell suspension we can control the initial size of the cell aggregate, thus influencing lineage commitment. In addition, these microwells are easily adaptable and scalable to most standard well plates and easily integrated into commercial liquid handling systems to provide an inexpensive and easy high throughput compound screening platform

Shrink-film microfluidic education modules: Complete devices within minutes

As advances in microfluidics continue to make contributions to diagnostics and life sciences, broader awareness of this expanding field becomes necessary. By leveraging low-cost microfabrication techniques that require no capital equipment or infrastructure, simple, accessible, and effective educational modules can be made available for a broad range of educational needs from middle school demonstrations to college laboratory classes. These modules demonstrate key microfluidic concepts such as diffusion and separation as well as “laboratory on-chip” applications including chemical reactions and biological assays. These modules are intended to provide an interdisciplinary hands-on experience, including chip design, fabrication of functional devices, and experiments at the microscale. Consequently, students will be able to conceptualize physics at small scales, gain experience in computer-aided design and microfabrication, and perform experiments—all in the context of addressing real-world challenges by making their own lab-on-chip devices