Metallization and Biopatterning on Ultra-Flexible Substrates via Dextran Sacrificial Layers

Citation: Tseng P, Pushkarsky I, Di Carlo D ( Metallization and Biopatterning on Ultra-Flexible Substrates via Dextran Sacrificial Layers Peter Tseng 0 Ivan Pushkarsky 0 Dino Di Carlo 0 Arum Han, Texas A&M University, United States of America 0 Department of Bioengineering, University of California Los Angeles , Los Angeles, California , United States of America Micro-patterning tools adopted from the semiconductor industry have mostly been optimized to pattern features onto rigid silicon and glass substrates, however, recently the need to pattern on soft substrates has been identified in simulating cellular environments or developing flexible biosensors. We present a simple method of introducing a variety of patterned materials and structures into ultra-flexible polydimethylsiloxane (PDMS) layers (elastic moduli down to 3 kPa) utilizing water-soluble dextran sacrificial thin films. Dextran films provided a stable template for photolithography, metal deposition, particle adsorption, and protein stamping. These materials and structures (including dextran itself) were then readily transferrable to an elastomer surface following PDMS (10 to 70:1 base to crosslinker ratios) curing over the patterned dextran layer and after sacrificial etch of the dextran in water. We demonstrate that this simple and straightforward approach can controllably manipulate surface wetting and protein adsorption characteristics of PDMS, covalently link protein patterns for stable cell patterning, generate composite structures of epoxy or particles for study of cell mechanical response, and stably integrate certain metals with use of vinyl molecular adhesives. This method is compatible over the complete moduli range of PDMS, and potentially generalizable over a host of additional micro- and nano-structures and materials. - Data Availability: The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper and its Supporting Information files. Funding: This work received support from a NIH New Innovator Award (#1DP2OD007113). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. Polydimethylsiloxane (PDMS) forms the base of a large proportion of microdevices, and has seen extensive use in microfluidics [1,2], flexible electronics [38], and in developing cell-material interfaces [915]. A large proportion of traditional devices are fabricated using the standard formulation, a 10:1 ratio of polymer base to crosslinker that possesses an elastic modulus of approximately 2 MPa. Ultra-flexible formulations of PDMS, which can be straightforwardly generated through increasing the base to cross-linker ratio up to 70:1, can typically achieve elastic moduli down below 3 kPa [14] which could have unique advantages for flexible electronics and as cell biology substrates. These flexible substrates, however, are relatively underutilized, particularly in terms of surface micromachining and in integration of these surfaces with complex microstructure. PDMS at this flexibility is unique to stiffer formulations in that they deflect under significantly lower stresses than standard PDMS, and their viscoelasticity lends a minor selfhealing quality to the layers. This could potentially yield a new avenue for flexible electronics, which often utilize composite structures of plastics and membranes of 10:1 PDMS. These ultraflexible substrates have found the most use in cell biology, as PDMS moduli can approximate the moduli of tissues at ratios of 70 to 50:1 base to crosslinker ratios. At the elastic moduli created with these formulations, cells can significantly deflect the substrate on their own, without macroscopic stimuli. These substrates are diversely utilized for traction force microscopy [12,13,16] (measuring deflections generated by cells), stem cell differentiation [17], studying cell polarization [9], in which the goal is often to assay how stiffness of the substrata can affect cellular behavior [18]. In general, however, surface micromachining or patterning of PDMS at these extremely soft formulations is not straightforward due to complications in manipulating this layer. The main issue stems from the fact that PDMS at these formulations is typically tacky, non-specifically adheres over a wide variety of surfaces, and is generally difficult to pattern [19]. For example, siloxanes designed for this elastic modulus (such as Sylgard 527) are commonly used as adhesives. Standard methods of lithographically patterning standard PDMS [20] (such as with SU-8) are incompatible with soft formulations of PDMS due to layer incompatibilities with solvents, and large stresses that form during processing. Oxygen plasma exposure, often used to improve adhesion to stiffer formulations of PDMS, is similarly not directly amenable to patterning on ultra soft layers due to the formation of brittle, easily cracked oxide monolayers [21,22]. Direct contact printing approaches similarly lead to poor pattern transfer due to deformation of the underlying PDMS substrate, and nonspecific interactions between stamps and the substrate [19]. Microstructure is commonly embedded in PDMS through physical demolding of PDMS from silicon substrates [2325]. The same issues with stamping are encountered in demolding, as nonspecific interactions and the weak physical nature of soft PDMS often leads to significant deformation or destruction of the elastomer layer. Water-soluble sacrificial layers have previously been studied as a method of releasing microstructure in surface micromachining [26]. These possess a number of advantages over traditional sacrificial layers, such as solvent or gas (ie. XeF2) based methods, namely their convenience in deposition and preparation (spincoating, and low temperature baking), and the broad compatibility of the aqueous release step. This release step also potentially makes this compatible with a number of ultra soft (elastic modulus , 30 kPa) hydrogels and polymers. Polyvinyl alcohol has seen initial work as either an intermediate, transfer carrier [27] for delicate structure fabricated on one substrate to another, or in transferring protein patterns onto PDMS and acrylamide hydrogels [19]. Despite its durability (it is stable as a free membrane), we found direct printing on these materials to be difficult due to poor adhesion of microstructure to native layers. In this work, we utilize water-soluble dextran thin films coated on rigid silicon wafers as a direct template for the stable lithographical patterning and deposition/adsorption of microand nano-scale features (Fig. 1). We found dextran, with proper surface treatment, to be a stable and durable host for these complex microstructures. Features patterned by this method are treated (if required), and directly crosslinked and/or (...truncated)