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A microfluidic system for generating compartmentalized microenvironments of tissues and organs in vitro and for independently perfusing the compartments. A microfluidic device that includes at least a first perfusion path and a second separate perfusion path. The microfluidic device also has a chamber containing a matrix, where the matrix surrounds at least one void whose lumen is in fluidic connection exclusively with the first perfusion path, where the at least one void can be populated with at least one cell type in such way that the cells are in direct contact with the matrix and the matrix is in fluidic connection exclusively with the second separate perfusion path.


Patent
Nortis Inc. | Date: 2011-08-17

A method for the creation of endothelial parent vessels from human vascular endothelial cells in vitro in a culture perfusion device (CPD) including a collagen chamber, inlet ports, a capillary tube, and an outlet port. A collagen solution is injected into the collagen chamber through a syringe needle until the chamber is filled with collagen. The CPD is perfused by filling the inlet ports and sequentially priming the inlet ports, and the outlet ports. A perfusable channel is created in the collagen chamber and a concentrated suspension of endothelial cells is injected into the inlet ports. The endothelial cells are injected into the at least one perfusable channel and incubated to attach to the walls of the perfusable channel. The cells are distributed within the CPD; and perfused to form a parent vessel having homogeneous monolayers of cells.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 299.99K | Year: 2013

Not Available


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 1.99M | Year: 2015

Not Available


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 225.00K | Year: 2015

DESCRIPTION provided by applicant The blood brain barrier BBB is a tight barrier formed by microvessels and capillaries that control the passage of nutrients fluids metabolic products and drugs between the blood and the brain Impaired function of the BBB is involved in a number of major pathologies afflicting the brain such as Alzheimerandapos s disease multiple sclerosis Parkinsonandapos s disease brain manifestations of AIDS stroke and cancer Although the neurotherapeutics sector is among the largest and fastest growing markets in the pharmaceutical industry progress is currently impaired by the lack of in vitro assays that reliabl predict in vivo BBB permeability None of the existing models adequately replicates the organotypic microenvironment of the BBB in which brain endothelial cells ECs pericytes PCs and astrocytes ACs are arranged in a characteristic architecture The proposed work utilizes organ on chip technology recently developed by Nortis Inc for creating D tissue microenvironments in disposable microfluidic chips The chip design enables the integration of living lumenally perfused microvasculature making it suitable for studying barrier function Strikingly extensive preliminary data indicate that human brain ECs PCs and ACs have the capacity to self assemble into a BBB like architecture within the Nortis chip This data will be leveraged to further develop and eventually commercialize BBB models of mouse and human The objective of Phase I is to achieve a model that replicates critical BBB functions of the mouse brain The mouse model will be developed and optimized for viability structure and function Expression of tight junction TJ proteins and the transporter P glycoprotein an important functional characteristic of the BBB will be measured Microvessel permeability will be assessed by perfusion with fluorescently labelled molecules Aim The model will then be challenged with the barrier modulating compound lipopolysaccharide LPS and evaluated for associated changes in TJ protein expression molecule permeability and leukocyte transendothelial migration Aim During Phase II the mouse BBB chip will be used to develop and qualify specific BBB assays such as transferrin receptor transporter activity BBB permeability challenge with LPS and stimuli induced leukocyte transmigration Aim Success criteria is an assay robustness of Zandapos Aim of Phase II is to develop a human BBB model The human model will be optimized to recapitulate key structural and functional features of the BBB including TJ formation permeability and transporter activity To demonstrate utility the model will be treated with LPS mannitol and angiotensin II and evaluated for associated changes in BBB structure and function Each of these compounds has clinical relevance but acts by a different mechanism Aim is to qualify specific human BBB assays and establish relevance to clinical data The products developed with support from this grant will significantly enhance progress in basic translational and clinical neuroscience research and will significantly advance therapy for numerous devastating diseases PUBLIC HEALTH RELEVANCE Impaired function of the blood brain barrier contributes to a number of diseases including Alzheimerandapos s disease multiple sclerosis Parkinsonandapos s disease malignancies of the brain and stroke The high failure rate of drugs targeting these disorders highlights the critical need for blood brain barrier models that better predict clinical outcomes Here microfluidic technology is utilized to develop two new in vitro models that replicate a number of key in vivo barrier functions providing an important alternative to current in vitro models and animal testing


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: STTR | Phase: Phase I | Award Amount: 365.00K | Year: 2016

DESCRIPTION provided by applicant The emerging field of stem cell therapy has the potential to transform medicine forever However a major bottleneck for bringing stem cell therapies to the patient is the lack of adequate in vitro assays for the study of stem cell quality Critical test criteria are efficacy pluripotency prior to the differentiation process and safety lack of tumorigenicity after differentiation prior to implantation of stem cell derived tissues The simplest assay available to assess stem cell quality is the embryoid body EB assay However this assay is not able to support tissue growth long enough to achieve complete teratoma development Therefore the present gold standard for testing stem cell quality relies on in vivo testing by injecting stem cell preparations into immunodeficient mice This so called andquot teratoma assayandquot assesses the stem cellsandapos pluripotency the ability to develop into cell types derived from all three embryonic germ layers Unfortunately this in vivo assay has significant drawbacks it requires a large number of animals is prohibitively expensive time consuming labor intensive and results are dependent on surgical skills The proposed projectandapos s objective is to develop an in vitro assay based on a microfluidic chip containing a tissue engineered vascularized humanized microenvironment for testing stem cell pluripotency Preliminary data obtained with the Nortis technology suggest that the proposed in vitro model can perform the pluripotency test much more economically and in a much shorter time frame than the in vivo teratoma assay Additionally our data indicate that perfused microvasculature incorporated into stem cell environment is key to long term viability and differentiation of human teratoma tissue During Phase I we will develop the microfluidic hardware and tissue engineering protocols Specific Aim Additionally we plan to demonstrate feasibility that the assay can be performed with a quality and robustness that complies with the requirements for assessing stem cell pluripotency Specific Aim We will compare the performance of our teratoma chip directly with currently available methods the EB assay and in vivo teratoma assay Minimum feasibility requirements for Phase I are to meet the performance quality and run time of the in vivo assay at significantly reduced costs During Phase II we will dedicate major Randamp D to validate the assay and increase throughput capabilities Ultimately the proposed product will provide researchers in academia and industry with a powerful new in vitro tool that will fuel the development of groundbreaking stem cell therapies and their clinical translation PUBLIC HEALTH RELEVANCE The emerging field of stem cell therapy has an enormous potential to transform medicine forever but lacks predictive tests for evaluating the quality of stem cells to be used in clinic The proposed project aims to develop an in vitro assay for evaluating stem cell quality based on a microfluidic chip containing a tissue engineered microenvironment that supports stem cell growth and differentiation Successfully accomplished project will provide researchers in academia and industry with a new generation in vitro tool that facilitates the discovery and development of new stem cell therapies and their translation to clinic across a wide range of human diseases


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 700.89K | Year: 2016

DESCRIPTION provided by applicant The blood brain barrier BBB is a tight barrier formed by microvessels and capillaries that control the passage of nutrients fluids metabolic products and drugs between the blood and the brain Impaired function of the BBB is involved in a number of major pathologies afflicting the brain such as Alzheimerandapos s disease multiple sclerosis Parkinsonandapos s disease brain manifestations of AIDS stroke and cancer Although the neurotherapeutics sector is among the largest and fastest growing markets in the pharmaceutical industry progress is currently impaired by the lack of in vitro assays that reliabl predict in vivo BBB permeability None of the existing models adequately replicates the organotypic microenvironment of the BBB in which brain endothelial cells ECs pericytes PCs and astrocytes ACs are arranged in a characteristic architecture The proposed work utilizes organ on chip technology recently developed by Nortis Inc for creating D tissue microenvironments in disposable microfluidic chips The chip design enables the integration of living lumenally perfused microvasculature making it suitable for studying barrier function Strikingly extensive preliminary data indicate that human brain ECs PCs and ACs have the capacity to self assemble into a BBB like architecture within the Nortis chip This data will be leveraged to further develop and eventually commercialize BBB models of mouse and human The objective of Phase I is to achieve a model that replicates critical BBB functions of the mouse brain The mouse model will be developed and optimized for viability structure and function Expression of tight junction TJ proteins and the transporter P glycoprotein an important functional characteristic of the BBB will be measured Microvessel permeability will be assessed by perfusion with fluorescently labelled molecules Aim The model will then be challenged with the barrier modulating compound lipopolysaccharide LPS and evaluated for associated changes in TJ protein expression molecule permeability and leukocyte transendothelial migration Aim During Phase II the mouse BBB chip will be used to develop and qualify specific BBB assays such as transferrin receptor transporter activity BBB permeability challenge with LPS and stimuli induced leukocyte transmigration Aim Success criteria is an assay robustness of Zandapos Aim of Phase II is to develop a human BBB model The human model will be optimized to recapitulate key structural and functional features of the BBB including TJ formation permeability and transporter activity To demonstrate utility the model will be treated with LPS mannitol and angiotensin II and evaluated for associated changes in BBB structure and function Each of these compounds has clinical relevance but acts by a different mechanism Aim is to qualify specific human BBB assays and establish relevance to clinical data The products developed with support from this grant will significantly enhance progress in basic translational and clinical neuroscience research and will significantly advance therapy for numerous devastating diseases PUBLIC HEALTH RELEVANCE Impaired function of the blood brain barrier contributes to a number of diseases including Alzheimerandapos s disease multiple sclerosis Parkinsonandapos s disease malignancies of the brain and stroke The high failure rate of drugs targeting these disorders highlights the critical need for blood brain barrier models that better predict clinical outcomes Here microfluidic technology is utilized to develop two new in vitro models that replicate a number of key in vivo barrier functions providing an important alternative to current in vitro models and animal testing


Trademark
Nortis Inc. | Date: 2016-01-12

Scientific apparatus and instruments, namely, bio-chips for research or scientific purposes, microchips for scientific experiments in laboratories; molecular chemistry apparatus and instruments, namely, laboratory chemical reactors, and plates, glass slides or chips and microchips having microfluidic circuits that can be used in chemical analysis, biological analysis or patterning for scientific, laboratory or medical research use in molecular laboratory apparatus and instruments; apparatus and instruments for scientific research in molecular laboratories, namely, liquid handling device for laboratory use; apparatus and instruments for use in compound screening, namely, laboratory instrument for the detection of compounds in the nature of pharmaceuticals and small biological molecules in a biological sample for research and diagnostic use; apparatus and instruments for use in molecular screening, namely, laboratory instrument for the detection of specific biological markers in a biological sample for research and diagnostic use; apparatus and instruments for use in molecular biological testing, namely, plates, glass slides or chips having multi-well arrays that can be used in chemical analysis, biological analysis, or patterning for scientific, laboratory or medical diagnostic research use in molecular laboratory apparatus and instruments; apparatus and instruments for use in genetic testing, namely, apparatus and instruments for processing relative DNA, RNA and nucleic acids, in the context of genetic applications; apparatus and instruments for use in molecular biological processing, namely, microfluidic dispensing, plates, glass slides or chips having microfluidic circuits that can be used in chemical analysis, biological analysis or patterning for scientific, laboratory or medical research and diagnostic use on related instruments and apparatus.


News Article | June 18, 2015
Site: www.xconomy.com

With J&J Deal, Emulate Nabs First Partner For Organ on Chip Tech If microchip systems that act like organs are ever going to really change preclinical drug development, it’s going to happen one experiment—and Big Pharma adopter—at a time. Emulate is trying to take on that challenge, and today it’s gotten its first supporter, Johnson & Johnson. Cambridge, MA-based Emulate, the “organ-on-a-chip” startup spun out of Harvard University’s Wyss Institute last year, is applying its technology—thumbnail-sized microchips that mimic how organs behave—to three of J&J’s preclinical drug programs. J&J, through its Janssen Biotech unit, is using the chips try to get a better read on how these drug candidates would affect human beings: Will they cause blood clots, or liver problems—the type of safety problems that have doomed various drugs in the past? “It really will help us in the near term begin to make decisions about which things we should advance and spend more time on,” says Michelle Browner, J&J’s senior director of platform innovation and partnership management, and a Roche executive for nearly two decades before that. Financial terms of the deal aren’t being disclosed; Emulate president and chief scientific officer Geraldine Hamilton would only say it enables the company to start generating revenue now, and get a piece of potential product sales down the road. She added that Emulate will announce at least three more similar partnerships this year, with other pharma players and companies in other industries like cosmetics and chemical-safety testing. These deals are, of course, small steps in a long and difficult journey for Emulate. It’s trying to convince drugmakers to change their R&D practices, and add microchips to other methods they typically use to get early look at how safe their products are. The need is significant, however. While preclinical testing of experimental drugs in petri dishes, and later animals, is the industry standard, even the most convincing data from these tests aren’t guaranteed to work in humans. That unpredictability often leads to clinical failures, many of which happen after millions of dollars have already been spent on their development. Emulate is one of a fast-growing group of players trying to change the paradigm with a technology designed to make preclinical testing more predictive of how drugs will perform in humans, and ultimately improve odds of success in clinical trials. Initially, Emulate hopes to complement current preclinical research methods; perhaps, one day, it will gather enough evidence that regulators will take notice and accept data from chip studies as a replacement, reducing the need for animal studies. That is particularly tall order that’ll likely take years to become a reality. “It’s obviously a very long goal, especially given the rate [at] which regulatory agencies change their practice, and what their requirements are, and rightly so,” Browner says. There’s also competition. Aside from other companies in the organ-on-chip space (CN Bio Innovations, a spin-out of the University of Oxford; Nortis, of Seattle; Tara Biosystems, of New York; and Netherlands-based Mimetas, to name a few), innovators are using other methods. Organovo Holdings, for example, uses 3-D printing techiques. Charlottesville, VA-based HemoShear Therapeutics has a way to see how blood flow affects cells in culture. There are plenty of others, each vying for the best way to help drugmakers get more reliable preclinical results. (Check out these features from Nature and The Economist for more.) Emulate is one of the more high-profile efforts to join the fray. It was incubated within the Wyss Institute for around four years, based on the work of its founder and a pioneer of the organ-on-a-chip field, Donald Ingber. Emulate raised around $40 million in grant money from the Defense Advanced Research Projects Agency (DARPA), and then spun out of the Wyss last July with a $12 million Series A and a team of about 30. As I wrote last year, Emulate claims that its chips provide a more detailed and representative look at biological function than those of its rivals—they include cells, blood flow, and use mechanical forces to mimic the function of an organ. Its lung chip, for instance, is infused with human lung cells and capillaries, and contracts and expands, mimicking breathing. Emulate has also been using the DARPA money in an effort to link several of its chips together to create a system that mimics the whole human body. Emulate’s plan is to forge a string of partnerships with pharma companies and iterate its own technology based on their needs. Browner says, for instance, that the lung chip intrigued J&J, and that has led the two companies to collaborate on an effort to recreate the conditions of thrombosis—blood clots—in a new microchip with Emulate’s technology. The results of that work will be submitted to a peer-reviewed publication this year, Hamilton says. That’s important to J&J, because it’s trying to understand how and why, for instance, certain cancer drug candidates can cause blood clots, and perhaps figure out how to avoid clots with future drugs. Emulate, meanwhile, gains the intellectual property for any new products that emerge from the collaborative work, meaning it could then sell these “thrombosis chips”—or whatever the next product is that the two create—to other companies too. Hamilton knows that for Emulate to make the type of broad impact it’s envisioning—to have technology that becomes a standard of drug R&D and, as Browner says, “sits on our lab benches”—the J&J deal must be just one of many examples of industry players using its chips. “The FDA understands the need for improved regulatory sciences, but [it] needs to see widespread adoption, and the generation of data from many different groups,” she says. “Long-term relationships with the end user—pharma partners, partners in the cosmetics industry going forward—are going to be really important.”

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