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University of Rochester and Simpore, Inc. | Date: 2014-10-27

Thin pnc-Si membranes operate as high-flow-rate EOPs at low applied voltages. In at least some instances, this may be due to the small electrical resistance presented by the membrane and high electric fields across the molecularly thin membrane. The normalized flow rates of some pnc-Si EOPs may be 20 times to several orders of magnitude higher than other low-voltage EOPs.

Agrawal A.A.,University of Rochester | Nehilla B.J.,University of Rochester | Reisig K.V.,Simpore, Inc. | Gaborski T.R.,University of Rochester | And 4 more authors.
Biomaterials | Year: 2010

Porous nanocrystalline silicon (pnc-Si) is new type of silicon nanomaterial with potential uses in lab-on-a-chip devices, cell culture, and tissue engineering. The pnc-Si material is a 15. nm thick, freestanding, nanoporous membrane made with scalable silicon manufacturing. Because pnc-Si membranes are approximately 1000 times thinner than any polymeric membrane, their permeability to small solutes is orders-of-magnitude greater than conventional membranes. As cell culture substrates, pnc-Si membranes can overcome the shortcomings of membranes used in commercial transwell devices and enable new devices for the control of cellular microenvironments. The current study investigates the feasibility of pnc-Si as a cell culture substrate by measuring cell adhesion, morphology, growth and viability on pnc-Si compared to conventional culture substrates. Results for immortalized fibroblasts and primary vascular endothelial cells are highly similar on pnc-Si, polystyrene and glass. Significantly, pnc-Si dissolves in cell culture media over several days without cytotoxic effects and stability is tunable by modifying the density of a superficial oxide. The results establish pnc-Si as a viable substrate for cell culture and a degradable biomaterial. Pnc-Si membranes should find use in the study of molecular transport through cell monolayers, in studies of cell-cell communication, and as biodegradable scaffolds for three-dimensional tissue constructs. © 2010 Elsevier Ltd. Source

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 184.66K | Year: 2011

DESCRIPTION (provided by applicant): Advances in protein and DNA microarrays have enabled dramatic increases in throughput and equipment standardization has made these techniques more commonplace. High density, high throughput microarrays reduce the cost of research and development in drug discovery and basic science by decreasing reagent volumes and increasing the number of experiments per plate. Missing from this miniaturization, however, are cell culture microarrays. Existing low well count cell cultureplates require greater volumes of precious drug formulations for permeability assays and more plates are required to complete a series of experiments. These same factors increase the cost of parallelized cellular experimentation in basic science such as screening stem cell culture differentiation conditions. In this proposal we will test the feasibility of using a new class of ultrathin nanoporous membrane to enable miniaturization of cell culture screening for high throughout drug permeability and co-culture studies. At the limit we will enable single cell screening to study phenotypic and behavioral variations in cell populations in response to stimuli, drug treatments or co-culture environments. In the first Aim of this work, we will fabricate microarray-scale cell culture arrays using porous nanocrystalline silicon (pnc-Si). We will confirm these devices and size format promote healthy growth of primary human umbilical vein endothelial cells by comparing cytotoxicity and growth curve measurements againstlarger conventional cell inserts. To test feasibility as a high throughout platform for single cell and co-culture screening, we will develop a microarray of wells on pnc-Si. Our approach is novel because we will be the first to offer a membranesupported microarray that enables study variations in populations of cancer cells, stem cells as well as primary cell response to drug treatment in a co-culture environment. In Phase II we will focus on drug screening and stem cell differentiation with the goal of developing an automated cell dispensing and fluorescent image analysis system. In both cases we will also pursue enlarged microarrays (gt100 microns) with degradable membrane supports, which will permit the growth a small islands of stratified tissue. Successful completion of Phase I will enable the launch of a live imaging research tool for small-scale cell co-culture. Within 6 months of completing Phase II, we will introduce a 384-window microarray system with gt105 wells. HEALTH RELEVANCE: SiMPore'spnc-Si membranes are a breakthrough technology 1,000x thinner than conventional and other nanoporous membranes, with permeability more than 100 times greater. These characteristics enable miniaturization of conventional cell culture and the development ofhigh---throughput screens for single cell co-culture research including stem cell differentiation, cancer cell response to drugs and tissue engineering.

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 155.82K | Year: 2011

DESCRIPTION (provided by applicant): Cryo electron microscopy is a powerful technique for generating 3-D images of macromolecules and their interactions with fine structure within cells. These materials are imbedded in their native state within a thin layer of amorphous ice for imaging in a transmission electron microscope. By taking a series of images at various angles, 3-D reconstructions can be made. However, these low-density materials produce little contrast in TEM images, and this effect is compoundedby the limited electron current that can be applied to these fragile samples before damage is likely to occur. One of the most promising methods to increase image clarity is through the use of phase contrast imaging where specially designed phase plates (Zernike phase plates in this work) are used to develop contrast between electrons that are scattered by the sample and those that pass directly through. Unfortunately, despite the availability of sophisticated microscopes that are designed to accept phaseplates, researchers are frustrated by the lack of consistently manufactured, high-quality phase plates. In this proposed project, extensive microfabrication expertise in the manufacture of ultrathin materials for EM grid applications is being applied to the problem of phase plate production. Through a collaboration between TEMWindows.com, a respected ultrathin membrane fabricator, and the Wadsworth Center, a pioneer in the development of cryo and phase contrast electron imaging, a series of phase platedesigns will be produced using well-controlled and manufacturable methods, and these devices will be directly compared to current carbon-based phase plates. The goal is to produce stable, consistent, and low cost phase plates that show little backgroundcharging over long duration in a TEM. PUBLIC HEALTH RELEVANCE: The project described in this proposal will provide a commercial source of contrast enhancing phase plates to remove a bottleneck and advance the development of cryo electron microscopy.This technique is used to study the 3-D structure of large molecules and how they interact with the complex structures within cells. This structural information is critical to understanding fundamental processes involved in various disease states that impact public health.

Agency: National Science Foundation | Branch: | Program: STTR | Phase: Phase I | Award Amount: 225.00K | Year: 2015

The broader impact/commercial potential of this Small Business Technology Transfer (STTR) Phase I project relates to the treatment of end-stage renal disease, a significant health burden in the US. Trends are moving toward patient-managed, in-home treatments. The goal of this proposal is to accelerate adoption of safer home hemodialysis therapy through development of prototype dialysis systems. Despite the recognized economic, health and quality-of-life benefits of more frequent hemodialysis treatments, adoption of home hemodialysis using present systems is being limited by doctors? and patients? safety concerns. Simpler and safer hemodialysis therapies will require breakthroughs in both device components and form-factors. The development of a small-scale, highly efficient dialysis system enabled by silicon nanomembranes holds potential for increasing adoption of home dialysis and its related benefits for the 430,000 individuals affected by end-stage renal disease in the US. The proposed project concerns the scale up of silicon nanomembranes, which offer extraordinary and unparalleled permeability, enabling small-scale hemodialysis. This project focuses on the optimization of membrane ?liftoff?methods which enable the release of large areas of silicon nanomembranes from silicon wafer supports on which they are produced, thereby simultaneously increasing active membrane area and reducing production cost. Fluidic housings will be developed for these membranes appropriate for blood volumes for large animal (Pig/sheep) and human scales. Bench-top validation will be conducted to measure toxin clearance and ultrafiltration in the prototype system.

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