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Phoenix, AZ, United States

Tenstad E.,Buskerud and Vestfold University College | Tourovskaia A.,VisionGate | Folch A.,University of Washington | Myklebost O.,University of Oslo | Rian E.,DiaGenic ASA
Lab on a Chip - Miniaturisation for Chemistry and Biology | Year: 2010

Microtechnology offers great prospects for cellular research by enabling controlled experimental conditions that cannot be achieved by traditional methods. This study demonstrates the use of a microfluidic platform for long-term cultivation (3 weeks) of human mesenchymal stem-like cells (MSCs), a cell population of high interest for tissue engineering. The typical high motility of the MSCs required a strategy for preventing cells from inhabiting the feeding channels and thus interfere with a steady perfusion of medium to the cell cultivation chamber. Hence, a straightforward and long-term patterning method was developed and implemented for reliable cell positioning within the device. This method was based on the modification of a polystyrene substrate into cell supportive and non-supportive regions by the use of selective oxygen plasma treatment and the triblock copolymer Pluronic. Also, a novel and size-effective "flip-chip" set-up for operating the devices was invented. Successful and reproducible adipogenic and osteogenic differentiation of MSCs in the device was demonstrated, verifying that an adequate long-term microfluidic cultivation environment was obtained. Strengths of the experimental protocol include ease of fabrication and maintenance (gravity driven), good cell performance (viability/differentiation), as well as the possibility of exposing the culture to heterogeneous laminar flow for experimental purposes. © The Royal Society of Chemistry 2010. Source


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 202.36K | Year: 2011

DESCRIPTION (provided by applicant): Disregulated angiogenesis-the growth of new blood-vessels from existing vasculature-plays a central role in more than 70 major health conditions including cancer, cardiovascular disease, and macular degeneration. More than one billion people worldwide are afflicted by angiogenesis-dependent diseases. Therapeutics that target blood-vessel growth promise new possibilities in the treatment of devastating diseases and have vast economic potential. However, progress in translation from basic research into the clinic is slowed by the lack of dependable models for angiogenesis research and drug testing. Presently, none of the existing in-vitro models for the study of angiogenesis integrates most of the critical elements that typify vascular growth in vivo, and none of the existing models includes the growth of capillary sprouts from existing blood vessels under flow- which is by definition the hallmark of angiogenesis. Previously, we have developed tissue-engineering techniques for the creation of microvessels within small fluidic devices. Within these devices, we generate luminally-perfused parent vessels from endothelial cells that subsequently sprout and form anatomizing capillary-like networks in collagen. We now propose to develop this method into an advanced in-vitro angiogenesis model with the following attributes: (1) tissue-engineered parent vessels mimicking architecture and cell composition in vivo, capable of angiogenic sprouting into a surrounding three-dimensional matrix; (2) human-derived cells; (3) direct luminal perfusion of parent vessels and sprouts; (4) tightly-controlled physical and chemical conditions; and (5) a mass produced, disposable fluidic device that can be adapted for the use in existing high-throughput analysis platforms. Aim 1 of the proposed project will be the completion of an optimized design of the fluidic device and the establishment of a system that allows for the tight control of perfusion, temperature, gas concentration and pH within the device. Aim 2 will be to achieve established techniques for the generation of microvasculature with the three structural key components of angiogenesis: endothelial cells, pericytes, and basement membrane. Once feasibility is established, we plan to advance ourmodel into a standardized, easy to use product that can be of significant value in the development of therapies for a range of devastating diseases. PUBLIC HEALTH RELEVANCE: Disregulated growth of blood vessels is a central element in cancer andother important diseases. More reliable assays and models for the study of vascular growth and the evaluation of therapeutic drugs are necessary to improve clinical results. We propose a new model for the study of vascular functions that closer mimics natural vessels.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 188.23K | Year: 2010

DESCRIPTION (provided by applicant): The study of the tumor microenvironment promises to lead to groundbreaking strategies for the therapy of cancer. Unfortunately, progress of this research is impaired by the lack of available models that recapitulate key features of the interaction between tumor cells, stroma, and vasculature in a 3D in-vitro environment. The National Cancer Institute has identified the development of such models as a high priority. The long-term objective of this project is the development of a vascularized in-vitro model of the tumor microenvironment. The basic components of this model are a disposable, perfused microfluidic device with a viewing chamber filled with an extracellular-matrix gel. Tubular channels are created within the gel into which endothelial cells are introduced to form parent vessels. The parent vessels are capable of angiogenic sprouting and the formation of capillary-like networks. The design of the fluidic device allows for direct luminal perfusion of the engineered vessels and sprouts. Cancer cells can be integrated into this model in various ways for studies including metastasis, tumor-angiogenesis, and the screening of cancer therapeutics. In its commercial version, the system will be self-contained, comprising fluidic pumps, reservoirs for growth medium, sensors, and an array of microfluidic devices. Aim 1 will focus on the microfabrication and quality-control testing of a commercially-viable device for an in-vitro tumor microenvironment model. All devices will be characterized for their ability to create perfusable parent vessels and the associated angiogenic sprouts. Aim 2 will establish the utility of the device for the study of extravasation, which is the process of cancer cells breaking through the endothelial lining of the vasculature to form metastases. Extravasation will be measured as the number of cancer cells which break through the vascular sprouts into the extracellular matrix. Two prostate-cancer cell lines of different metastatic potential will be compared to a normal prostate cell line. The successful completion of these studies presents an important step toward the development of a new generation of tumor- microenvironment models that can be standardized and made commercially available to a broad community of researcher in academia and industry. PUBLIC HEALTH RELEVANCE: The study of the organ-specific environment in which tumors grow and spread is crucial for developing new cancer therapeutics. Unfortunately, progress is impaired by the lack of available research tools. We propose the development of a model that mimics the natural tumor environment, including perfused blood vessels and capillaries. We expect our model to become a valuable system in cancer research, commercially available to scientists in academia and industry.


Trademark
VisionGate | Date: 2014-10-30

Medical software platform for evaluating and annotating 2D and 3D cell sputum specimen image data identified as suspicious for dysplasia or cancer; medical software platform for evaluating and annotating 2D and 3D cell image data in the fields of cancer, tissue-based diagnostic testing, cytology and cell-based testing. Instrument and apparatus systems for medical diagnostic uses consisting of a cytology review workstation for evaluating and annotating 2D and 3D cell sputum specimen image data identified as suspicious for dysplasia or cancer, and software sold therewith as a unit; instrument and apparatus systems for medical diagnostic uses consisting of a cytology review workstation for evaluating and annotating 2D and 3D cell image data in the fields of cancer, tissue-based diagnostic testing, cytology and cell-based testing, and software sold therewith as a unit. Providing on-line, non-downloadable, Internet-based medical software platform for evaluating and annotating 2D and 3D cell sputum specimen image data identified as suspicious for dysplasia or cancer; providing on-line, non-downloadable, Internet-based software platform for medical software platform for evaluating and annotating 2D and 3D cell image data in the fields of cancer, tissue-based diagnostic testing, cytology and cell-based testing.


Patent
VisionGate | Date: 2010-08-24

An optical tomography system for viewing an object of interest includes a microcapillary tube viewing area for positioning the object of interest in an optical path including a detector. A motor is located to attach to and rotate a microcapillary tube. A device is arranged for transmitting broadband light having wavelengths between 550 nm and 620 nm into the microcapillary tube viewing area. A hyperchromatic lens is located to receive light transmitted through the microcapillary tube viewing area. A tube lens is located to focus light rays transmitted through the hyperchromatic lens, such that light rays from multiple object planes in the microcapillary tube viewing area simultaneously focus on the at least one detector.

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