CHAPEL HILL, NC, United States
CHAPEL HILL, NC, United States

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Cribb J.,University of North Carolina at Chapel Hill | Osborne L.D.,University of North Carolina at Chapel Hill | Hsiao J.P.-L.,University of North Carolina at Chapel Hill | Vicci L.,University of North Carolina at Chapel Hill | And 7 more authors.
Review of Scientific Instruments | Year: 2015

In the last decade, the emergence of high throughput screening has enabled the development of novel drug therapies and elucidated many complex cellular processes. Concurrently, the mechanobiology community has developed tools and methods to show that the dysregulation of biophysical properties and the biochemical mechanisms controlling those properties contribute significantly to many human diseases. Despite these advances, a complete understanding of the connection between biomechanics and disease will require advances in instrumentation that enable parallelized, high throughput assays capable of probing complex signaling pathways, studying biology in physiologically relevant conditions, and capturing specimen and mechanical heterogeneity. Traditional biophysical instruments are unable to meet this need. To address the challenge of large-scale, parallelized biophysical measurements, we have developed an automated array high-throughput microscope system that utilizes passive microbead diffusion to characterize mechanical properties of biomaterials. The instrument is capable of acquiring data on twelve-channels simultaneously, where each channel in the system can independently drive two-channel fluorescence imaging at up to 50 frames per second. We employ this system to measure the concentration-dependent apparent viscosity of hyaluronan, an essential polymer found in connective tissue and whose expression has been implicated in cancer progression. © 2015 AIP Publishing LLC.


Judith R.M.,University of North Carolina at Chapel Hill | Fisher J.K.,Rheomics, Inc. | Spero R.C.,Rheomics, Inc. | Fiser B.L.,High Point University | And 8 more authors.
Lab on a Chip - Miniaturisation for Chemistry and Biology | Year: 2015

We present a novel technology for microfluidic elastometry and demonstrate its ability to measure stiffness of blood clots as they form. A disposable micro-capillary strip draws small volumes (20 μL) of whole blood into a chamber containing a surface-mounted micropost array. The posts are magnetically actuated, thereby applying a shear stress to the blood clot. The posts' response to magnetic field changes as the blood clot forms; this response is measured by optical transmission. We show that a quasi-static model correctly predicts the torque applied to the microposts. We experimentally validate the ability of the system to measure clot stiffness by correlating our system with a commercial thromboelastograph. We conclude that actuated surface-attached post (ASAP) technology addresses a clinical need for point-of-care and small-volume elastic haemostatic assays. © The Royal Society of Chemistry 2015.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 481.08K | Year: 2012

DESCRIPTION (provided by applicant): Population studies and drug research require a high-throughput measurement of clot stiffness, permeability. The single largest cause of death in the US over the latter half of the 20 century was and still is a thrombotic event: a clot in the heart, brain, or lungs. Assessing clot quality is essential for studying, diagnosing, and treating disease Conventional blood coagulation tests can be grouped into three areas: clotting time, mechanical stability, and permeability.Clot stiffness and permeability are correlated with a broad range of diseases, but because they are not available in high throughput screening (HTS) format, the tests are under-applied. An HTS system for these tests would illuminate the relationship of disease etiology and abnormalities of blood clots, enable large- population screens, and speed development of new pharmaceuticals. We anticipate that these measurements will one day provide superior clinical monitoring for patients receiving treatment thatmodifies thrombotic activity. With this Phase 1 SHIFT SBIR Rheomics will develop a triple-analysis of clotting that uses small beads. Clotting time is measured by seeing microbeads (1-5 5m) become trapped in a forming clot. Mechanical Stability is measured by tugging on microbeads using our patented magnetic force technology. Permeability is measured using a novel technique invented by the PI/PD, in which hindered diffusion of nanoparticles is used to derive the clot's permeability by applying the effective medium theory. This Phase 1 SBIR will test the feasibility of an HTS triple-analysis that will simultaneously and automatically measure clot kinetics, strength, and permeability. This Phase 1 SBIR comprises two specific aims: assembling an imaging/magnetics platform to perform the tests, and validating the tests against standard coagulometers. We are aware of no existing system (commercial or otherwise) that can perform all three measurements, let alone perform them simultaneously, automatically, orin high throughput. In success, the Rheomics triple-analysis will deliver a stiffness assay that, unlike existing techniques, can be scaled to high throughput (eg, 96-well tray) format, and a permeability assay that is up to 60x faster, fully automated, and uses small sample volumes. Rheomics is uniquely positioned to deliver on these aims. Our team features an intersection of expertise in optical and magnetic systems development, soft-matter physics, and technology commercialization, including key personnel who patented, developed, and transferred for commercialization the technology behind the widely adopted CoaguChek(R) System, and who founded Cardiovascular Diagnostics, a successful IPO. PUBLIC HEALTH RELEVANCE: Rheomics is developing a coagulometer that will simultaneously measure clotting time, clot stiffness, and clot permeability in a high throughput, small volume format that is up to 60x faster than existing techniques. This system will advance scientific research into blood clot structureand function, enable large-population clinical research studies, and speed development of new pharmaceuticals.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 297.09K | Year: 2016

of Hospital acquired infection that leads to sepsis is deadly expensive and increasingly common Rapid diagnosis anti microbial treatment and identification of the pathogen strain is key to improving outcomes and reducing costs Diagnosis and strain identification must improve Novel techniques for blood culture BC and molecular diagnostics MDx are promising but better technology for pathogen purification and concentration from blood will be essential for the next generation of diagnostics We will develop a device to purify and concentrate pathogens directly from a large volume mL of whole blood Unlike existing techniques our technology will achieve the high binding efficiency of a filter with the non clogging properties of an empty flow cell of A device to purify and concentrate pathogens directly from a large volume of whole blood will be developed with the goal of improving improve blood culture and molecular diagnostics


Grant
Agency: National Science Foundation | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 146.03K | Year: 2016

The broader impact/commercial potential of this project is to enable smaller diagnostic systems and smaller blood draws without compromising on sample quality and time-to-result. Currently, clinicians who want to ensure that blood samples are well stabilized must use test tubes 1 mL or larger. Meanwhile, point-of-care tests that use smaller volumes are challenged to disperse analytic reagents rapidly and evenly throughout the volume. This project will develop a microfluidic platform for rapid dispersal of dried reagents in whole blood. This Small Business Innovation Research (SBIR) Phase I project tackles a vexing technical challenge. Mixing is hard to achieve in microfluidic systems due to the lack of turbulence. In these so-called low Reynolds number environments, a solute will only move relative to its solvent by diffusion. Depending on the temperature, the size of the solute, and the viscosity of the solvent, mixing across a millimeter-scale chamber can take minutes or even hours. This project will demonstrate a low-power, non-destructive microfluidic mixing technology to rapidly disperse dried reagents into blood. The goal is to accelerate time-to-completion by as much as 10x.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 197.46K | Year: 2015

DESCRIPTION provided by applicant Rheomics is developing a global hemostasis test that uses whole blood It will enable faster diagnosis and goal directed therapy of coagulopathies associated with trauma It will reduce morbidity mortality and costs associated with blood product therapy Our device measures clotting time kinetics stiffness and lysis Unlike existing devices ours will use an inexpensive disposable microfluidic test strip and a robust easy to use analyzer Our goal is to improve care for the many patients as many as million just in the US who develop a coagulation dysfunction that triples their chance of dying At the same time we can save hundreds of dollars per patient and hundreds of thousands of dollars for hospital systems PUBLIC HEALTH RELEVANCE Rheomics is developing a global hemostasis test that uses whole blood It will improve care for more than million patients who develop trauma induced coagulopathy and reduce spending on blood product saving hundreds of dollars per patient and hundreds of thousands of dollars for hospital systems


Grant
Agency: NSF | Branch: Standard Grant | Program: | Phase: | Award Amount: 146.03K | Year: 2016

The broader impact/commercial potential of this project is to enable smaller diagnostic systems and smaller blood draws without compromising on sample quality and time-to-result. Currently, clinicians who want to ensure that blood samples are well stabilized must use test tubes 1 mL or larger. Meanwhile, point-of-care tests that use smaller volumes are challenged to disperse analytic reagents rapidly and evenly throughout the volume. This project will develop a microfluidic platform for rapid dispersal of dried reagents in whole blood.


This Small Business Innovation Research (SBIR) Phase I project tackles a vexing technical challenge. Mixing is hard to achieve in microfluidic systems due to the lack of turbulence. In these so-called low Reynolds number environments, a solute will only move relative to its solvent by diffusion. Depending on the temperature, the size of the solute, and the viscosity of the solvent, mixing across a millimeter-scale chamber can take minutes or even hours. This project will demonstrate a low-power, non-destructive microfluidic mixing technology to rapidly disperse dried reagents into blood. The goal is to accelerate time-to-completion by as much as 10x.


Trademark
Rheomics, Inc. | Date: 2016-06-07

Film components for microfluidic instruments and devices.


Trademark
Rheomics, Inc. | Date: 2016-06-07

Film components for microfluidic instruments and devices.


PubMed | Rheomics, Inc. and University of North Carolina at Chapel Hill
Type: Journal Article | Journal: The Review of scientific instruments | Year: 2015

In the last decade, the emergence of high throughput screening has enabled the development of novel drug therapies and elucidated many complex cellular processes. Concurrently, the mechanobiology community has developed tools and methods to show that the dysregulation of biophysical properties and the biochemical mechanisms controlling those properties contribute significantly to many human diseases. Despite these advances, a complete understanding of the connection between biomechanics and disease will require advances in instrumentation that enable parallelized, high throughput assays capable of probing complex signaling pathways, studying biology in physiologically relevant conditions, and capturing specimen and mechanical heterogeneity. Traditional biophysical instruments are unable to meet this need. To address the challenge of large-scale, parallelized biophysical measurements, we have developed an automated array high-throughput microscope system that utilizes passive microbead diffusion to characterize mechanical properties of biomaterials. The instrument is capable of acquiring data on twelve-channels simultaneously, where each channel in the system can independently drive two-channel fluorescence imaging at up to 50 frames per second. We employ this system to measure the concentration-dependent apparent viscosity of hyaluronan, an essential polymer found in connective tissue and whose expression has been implicated in cancer progression.

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