WEST HENRIETTA, NY, United States
WEST HENRIETTA, NY, United States

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Patent
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.


Grant
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.


The present invention is drawn to methods for facilitating fluid flow through the nanopores of membranes, i.e., through sub-micron pores. The present invention is also directed to one or more apparatus for such fluid flow, and for nanoporous membranes modified to facilitate such fluid flow.


Provided are nanoporous silicon nitride membranes and methods of making such membranes. The membranes can be part of a monolithic structure or free-standing. The membranes can be made by transfer of the nanoporous structure of a nanoporous silicon or silicon oxide film by, for example, reactive ion etching. The membranes can be used in, for example, filtration applications, hemodialysis applications, hemodialysis devices, laboratory separation devices, multi-well cell culture devices, electronic biosensors, optical biosensors, active pre-concentration filters for microfluidic devices.


Provided is a free-standing silicon oxide film that is under tensile stress. Also, provided are methods of making a free-standing silicon oxide film that is under tensile stress. The methods use low-power PECVD deposition of silicon oxide. Methods of imaging one or more objects (e.g., cells) using a free-standing silicon oxide film that is under tensile stress is also provided.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 153.25K | Year: 2010

DESCRIPTION (provided by applicant): In this Phase I application we will examine the feasibility of producing high yield porous nanocrystalline silicon (pnc-Si) membranes for protein purification products. Membranes made of this material are a breakthrough technology, 1000x thinner than conventional and other nanoporous membranes, with tunable pore sizes (5-100 nm) and precise distributions. At just tens of nanometers thick, pnc-Si membranes have no internal void spaces, resulting in minimal loss of filtrate and high permeability, making them ideally suited for rapid and precise biomolecule separations. Research of cellular components and proteins has risen to new levels with advances in separation tools such as two-dimensional liquid chromatography and capillary electrophoresis systems. These tools, however, are typically limited to core facilities at major research centers away from the bench top or the daily workspace of the average biomedical scientist. Laboratory separation and sample- prep tools haven't kept pace with advances in major core facilities. This is in part due to the fact that basic membrane technology has not significantly advanced in decades, still suited best to concentration or micron-scale separations. Pnc-Si membranes will enable consumable separation products that bridge the gap between bench top tools and core facility equipment. In this project we will test the feasibility of scalable production of pnc-Si membranes at reproducible pore sizes with adequate burst pressures to be integrated into stackable membrane modules. We will perform protein concentration and purification experiment using pnc-Si membranes in series and benchmark against industry standard centrifugal spin-tubes. Phase II efforts will fabricate stackable modules with precise cut-offs that fractionate and concentration complex protein mixtures in one pass with the goal of offering chromatography features with the speed and simplicity of membrane filtration. PUBLIC HEALTH RELEVANCE: SiMPore's pnc-Si membranes are a breakthrough technology 1000x thinner than conventional and other nanoporous membranes, with permeability more than 100 times greater and controllable tight pore size distributions. These characteristics enable protein separation and purification with the precision of liquid chromatography, but the speed and simplicity of a membrane filter.


Grant
Agency: NSF | Branch: Standard Grant | Program: | Phase: STTR 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.


Grant
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.


Grant
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.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: STTR | Phase: Phase I | Award Amount: 198.94K | Year: 2016

DESCRIPTION provided by applicant The global market for nanoparticles NP in biotechnology drug development and drug delivery was estimated to be $ B for and is expected to reach more than $ B by The two most active areas of product development are NPs for drug delivery and for in vivo imaging In these applications it is often critical that he outer surfaces of NPs are functionalized with antibodies Ab that target them to speci c tissues After functionalizing NPs with Abs it is necessary to remove unbound Ab from the NP preparation because any free Ab will compete with the NPs for target tissues Given the similar sizes of Ab nm and NPs this ubiquitous clean up step is challenging and represents a current pain in the market place Both academic and industrial NP scientists report that existing polymer based membranes are not capable of performing this separation and that they must resort to more time consuming complex and lower yield techniques such as size exclusion chromatography or dialysis Membrane based methods are preferred because of their simplicity ef ciency and scalability In this proposal we will realize a near term straight forward produc development opportunity that will result in a solution to the NP Ab separation problem Using SiMPoreandapos s nanomembranes in a custom centrifuge con guration we have recently shown the ability to separate Ab from nm polystyrene particles Additional innovations in membrane fabrication and non fouling coatings will allow us to pursue the following goals to develop and evaluate a SiMPore product prototype based on our preliminary custom centrifuge concept to produce a suf cient number of prototypes to enable beta testing at two major life science tool suppliers and to introduce a validated product upon completion of this month Phase I project PUBLIC HEALTH RELEVANCE This proposal focuses on developing laboratory tools for removing antibodies from nano particle conjugations Antibody conjugated nano particles are useful for both research and diagnostic purposes Our tools will help increase the specificity of these preparations

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