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SAINT LOUIS, MO, United States

Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 120.59K | Year: 2009

DESCRIPTION (provided by applicant): Despite decades of research focused mainly on gene transfection, effective intracellular delivery of biologically relevant material remains a difficult task, inhibiting research in a variety of biological and biomedical fields. This proposed work describes a commercially viable intracellular nanomaterial delivery device, the Electrosonic Ejector Microarray (EEM), that is optimized for drug and / or gene / nucleic acid and / or imaging agent delivery into cells via precise control of biophysical action (i.e., concurrent application of sono / mechanoporation, electroporation and thermoporation). The EEM is a novel microelectromechanical systems (MEMS)-enabled device that ejects a sample containing biological cells through microscopic nozzles with incorporated electroporation electrodes, thereby opening pores in the cell membrane via combined mechano / electroporation for uptake of nanomaterials.1 The high ultrasonic frequency of operation and a parallel (array) format enable fast processing of large cell populations at rates between 1 and 100 million cells per second; however, the device can potentially accommodate a wide range of sample sizes, from ~100 nL to arbitrarily large volumes when operated in continuous-flow mode. In addition, the device can be made disposable to eliminate cross-contamination and provides uniform (i.e., identical across an entire cell population) treatment on a single-cell level, which are critical capabilities for sample preparation in clinical applications of cell biology and gene therapy. The EEM is well-suited to basic / applied research, as well as diagnostic and therapeutic uses. Initial investigations will focus on cancer therapies combining mature recombinant protein therapies with emerging RNA interference (RNAi) technologies. The improved understanding of the relationship between the EEM operating parameters and realized bioeffects that will be gained through this proposed work is directly transferable to other application spaces. The primary objective of the proposed work is to develop a commercially viable EEM that demonstrates quantitative performance improvement over currently available nanomaterial delivery technologies. To achieve this objective, (1) an EEM platform that is optimized for cell treatment will be developed, (2) safe treatment of a variety of cell types and characterization of nanomaterial localization will be demonstrated, and (3) the transfection capabilities of the EEM will be optimized and its advantages over traditional transfection technologies quantified. PUBLIC HEALTH RELEVANCE: Development of the Electrosonic Ejector Microarray (EEM) will address the deficiencies of current intracellular drug / gene delivery techniques, which are inhibiting research in a variety of biological and biomedical fields. In particular, successful use of the EEM in development of therapies to treat glioblastomas, which are the most common and lethal brain tumors, will prove its feasibility in a wide range of drug discovery and gene therapy applications.


Opencell Technologies, Inc. | Entity website

By unlocking a new dimension of biomechanical cell treatment, our approach enables researchers to overcome existing obstacles to development and discovery in the life sciences


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 1.01M | Year: 2011

DESCRIPTION (provided by applicant): The ability to introduce drugs, genes, nucleic acids, and/or imaging agents into living cells is critical to drug design and delivery, as well as many cell biology and genetic modification protocols; however, currentlyavailable physical and reagent-based techniques are inadequate for applications requiring transfection of difficult-to-transfect cells (e.g., primary and stem cells). For this reason, transfection of nucleic acids into cells has become a significant challenge in the development of RNAi therapies and stem cell clinical applications. The technology that is the subject of this project proposal has demonstrated the potential to significantly impact these areas by enabling investigations of difficult-to-transfect cells, which are not currently feasible. The proposed work addresses this challenge through development of a microfabricated technology that enables treatment of arbitrarily sized cell populations on a cell-by-cell basis. STEAM (Single-sample Treatment via Electrosonic Actuation Microarray) ejects biological cells through microscopic nozzles with incorporated electroporation electrodes, thereby opening pores by concurrent mechanical and electrical disruption of the cell membrane. The parallel microarray format is scalable to accommodate discrete sample volumes from ~100 nl to tens of ml; however, in continuous-flow mode, the same device can rapidly process cells at 1 to 100 million cells per second. The critical advantage of STEAM is the uniformity of treatment experienced by each cell in a population, which is the key to achieving high transfection efficiency. During the SBIR Phase I project a prototype STEAM device demonstrated successful treatment of laboratory established cell lines. Device operating parameters were optimized using a small fluorescent molecule to evaluate uptake and cell viability. In addition, STEAM achieved trasfection efficiencies of 80% (mechanical poration) and gt90% (mechanical + electroporation) for GFP-encoding plasmid into HEK293 cells with cell viability gt70%, which is on par with lipofection and the best commercially available electroporation systems. The primary objectives of this SBIR Phase II project are further device refinement and optimization towards development of a production prototype and direct comparison with available physical and reagent-based techniques for transfection of difficult cells. To achieve these objectives, (1) a stand-alone STEAM system with disposable cartridge-based sample handling and on-board electronic control of both mechanical and electroporation parameters will be developed, and (2) a direct comparison of STEAM, commercial electroporation systems, lipofectamine-mediated transfection, and lentiviral gene transfer in difficult cells (including primary cancer stem cells from glioblastoma multiforme) will be performed. PUBLIC HEALTH RELEVANCE: Development of the STEAM (Single-sample Treatment via Electrosonic Actuation Microarray) platform will address the current need for alternative gene transfer solutions for use with difficult-to-transfect cells (e.g., primary and stem cells). The lack of successful commercial gene transfer solutions limits research in the life sciences and biomedical fields. STEAM addresses the need for effective, high-throughput, and scalable techniques to achieve transfection of difficult cells.


Meacham J.M.,Opencell Technologies, Inc. | O'Rourke A.,Opencell Technologies, Inc. | Yang Y.,Opencell Technologies, Inc. | Fedorov A.G.,Opencell Technologies, Inc. | And 2 more authors.
Journal of Manufacturing Science and Engineering, Transactions of the ASME | Year: 2010

The recent application of inkjet printing to fabrication of three-dimensional, multilayer and multimaterial parts has tested the limits of conventional printing-based additive manufacturing techniques. The novel method presented here, termed as additive manufacturing via microarray deposition (AMMD), expands the allowable range of physical properties of printed fluids to include important, high-viscosity production materials (e.g., polyurethane resins). AMMD relies on a piezoelectrically driven ultrasonic printhead that generates continuous streams of droplets from 45 ̃m orifices while operating in the 0.5-3.0 MHz frequency range. The device is composed of a bulk ceramic piezoelectric transducer for ultrasound generation, a reservoir for the material to be printed, and a silicon micromachined array of liquid horn structures, which make up the ejection nozzles. Unique to this new printing technique are the high frequency of operation, use of fluid cavity resonances to assist ejection, and acoustic wave focusing to generate the pressure gradient required to form and eject droplets. We present the initial characterization of a micromachined print-head for deposition of fluids that cannot be used with conventional printing-based rapid prototyping techniques. Glycerol-water mixtures with a range of properties (surface tensions of ̃58-73 mN/m and viscosities of 0.7-380 mN s /m2) were used as representative printing fluids for most investigations. Sustained ejection was observed in all cases. In addition, successful ejection of a urethane-based photopolymer resin (surface tension of ̃25-30 mN/m and viscosity of 900-3000 mN s /m2) was achieved in short duration bursts. Peaks in the ejection quality were found to correspond to predicted device resonances. Based on these results, we have demonstrated the printing of fluids that fall well outside of the accepted range for the previously introduced printing indicator. The micromachined ultrasonic print-head achieves sustained printing of fluids up to 380 mN s /m2, far above the typical printable range. Copyright © 2010 by ASME. Source


Garimella S.,Georgia Institute of Technology | Determan M.D.,Georgia Institute of Technology | Meacham J.M.,Opencell Technologies, Inc. | Lee S.,University of Nevada, Reno | Ernst T.C.,Cummins Inc.
International Journal of Refrigeration | Year: 2011

A novel miniaturization technology for binary-fluid heat and mass exchange was developed and numerous components were fabricated for demonstration as different parts of an ammonia/water absorption heat pump. Short lengths of microchannel tubes are placed in an array, with several such arrays stacked vertically. The ammonia/water solution flows in falling film/droplet mode on the outside of the tubes while coupling fluid flows through the microchannels. Coupling fluid heat transfer coefficients are extremely high due to the use of microchannel tubes. Effective vapor-solution contact on the absorption side minimizes heat and mass transfer resistances. This concept addresses all the requirements for absorber design in an extremely compact geometry. The technology is suitable for almost all absorption heat pump components (absorbers, desorbers, condensers, rectifiers, and evaporators) and for a wide range of binary-fluid processes. The development of several components for absorption and desorption at different capacities using this technology is reported here. © 2011 Elsevier Ltd and IIR. All rights reserved. Source

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