Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 228.59K | Year: 2013
DESCRIPTION (provided by applicant): For twenty years prolonged extracorporeal life support (ECLS ECMO) has been standard treatment for infants with severe heart or lung failure unresponsive to other treatment. The healthy survival rate in over 30,000 cases ranges from 40% in cardiac arrest to 95% in meconium aspiration. Improved treatment has resulted in decreased need for ECMO in full term neonatal respiratory failure, but the application to respiratory failure in older infants, cardiac failure, and sepsis is increasing. The devices used fr ECMO are individual components from several manufacturers, assembled on site, and used off label. Recently three companies have combined the devices into an integrated ECMO system. These are designed for older children and adults but require substantial modification for infants. The goal of this project is to design, test, and produce a life support system specifically for infants (1 through 10 kg, 1 day to 2 years age); we call this MiniECMO. Phase l aims include integration of the MC3 BioLung and MPump devices with cartridge heat modules and an automated sweep gas controller. The system will be coated with our unique nonthrombogenic NO secreting polymer to decrease or eliminate the need for systemic anticoagulation.The prototype system will be fabricated and tested in vitro to demonstrate safety, efficacy and durability. A pilot in vivo study will be conducted to measure durability of gs exchange, properties of the MiniLung, and to evaluate thrombogenicity. Phase llwill include extended testing of MiniECMO for safety and efficacy, development of a clinical ready device, and a clinical trial for ten patients conducted under an investigational device exemption (IDE). The University of Michigan Extracorporeal Life Support Lab and Michigan Critical Care Consultants are the leaders in this field and can bring this technology to reality in four years. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: The value of prolonged extracorporeal life support for infantsis well established. The success of this technology has been accomplished using a variety of devices that are designed for older children and adults, but are not well suited for infants. The goal of this research project is to design and produce a life support system specifically for infants, called MiniECMO, which will make the entire technology safer, simpler, and less expensive for current and future applications.
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 1.26M | Year: 2015
DESCRIPTION provided by applicant There are million births in the United States each year of which are premature Prematurity is associated with substantial mortality morbidity and escalating cost The complications of premature birth include respiratory gastrointestinal and central nervous system morbidity and significant mortality Many of these complications are caused directly or indirectly by our attempts to ventilate the immature lungs and reverse fetal circulation Although many of these babies recover with conventional management the mortality and morbidity of extremely low gestational age newborns ELGANs defined as born more than months before the expected date of birth is very high The current approach of positive pressure gas ventilation carries high risks of mechanical trauma and oxygen toxicity to the lungs A major paradigm shift in the post natal treatment of prematurity would be to avoid the complications of positive pressure ventilation and recreate the fetal environment with an Artificial Placenta AP which consists of four unique features maintaining fetal circulation and environment no mechanical ventilation simulated fetal breathing with fluid filled lungs and a novel form of a pump driven veno venous extracorporeal life support VV ECLS circuit with inflow via the umbilical vein and outflow via the right internal jugular vein Our collaborators at the University of Michigan Extracorporeal Life Support Lab ECLS Lab have demonstrated feasibility and reproducibility of complete extracorporeal support with medical components to simulate an artificial placenta for up to days with hemodynamic stability excellent gas exchange stable cerebral perfusion and maintenance of fetal circulation without mechanical ventilation The goal of this research project is to design and produce an integrated system that will function as an Artificial Placenta for the post natal treatment of very premature infants andlt weeks gestational age Our system will support ELGANs in the most natural state i e fetal circulation and is truly innovative and offers many therapeutic opportunities when compared to current clinical practice with mechanical ventilation Phase l aims include integration of the MC BioLung and MPump devices with cartridge heat modules and an automated sweep gas controller The system will be coated with our unique nonthrombogenic NO secreting polymer to decrease or eliminate the need for systemic anticoagulation The prototype system will be fabricated and tested in vitro to demonstrate safety efficacy and durability A pilot in vivo study will be conducted to demonstrate effective fetal circulation Phase ll will include extended in vivo testing of AP for safety and efficacy and the development of a clinical ready device The University of Michigan Extracorporeal Life Support Lab and MC are the leaders in this field and can bring this technology to reality in four years This project has high translational potential and would impact substantially upon the care of high risk premature newborns Successful completion of this research will lead to a clinical trial in moribund premature infants PUBLIC HEALTH RELEVANCE The goal of this research project is to design produce and test an integrated system that will comprise an Artificial Placenta AP for the post natal treatment of very premature infants andlt weeks gestational age This proposal has high translational potential and would impact substantially upon the care of high risk premature newborns
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 813.57K | Year: 2015
DESCRIPTION provided by applicant The use of ECMO in conjunction with CPR a technique known as andquot ECPRandquot has been shown to reduce central nervous system CNS damage improve brain function after recovery and result in survival to hospital discharge rates up to A limiting factor for widespread adoption of ECPR is the need for a simple automatic perfusion system that is inherently safe and provides full support with minimal operator intervention Developed under SBIR funding HL MC andapos s patented technologies have been combined to form a compact highly portable safe and simple to use automatic perfusion system APS This device will lower the barriers for implementation of emergent ECPR and facilitate expanded use of these procedures resulting in improved outcomes for refractory cardiac arrest The APS system is also envisioned as a tool for salvaging donor organs after cardiac death DCD The user requirements for DCD support and ECPR are equivalent allowing broader application of the APS in the expanding field of extracorporeal support In Phase I and II a prototype was developed for use in bench and animal testing and customer evaluations In vivo studies demonstrated restoration of cardiac function with ECPR after minutes of untreated ventricular fibrillation Additional studies with controlled and uncontrolled DCD animal models confirmed device functionality and demonstrated conditioning of organs to transplant status following extended periods of warm ischemia up to minutes Paramedical personnel were trained on the use of MC system and assisted in animal studies to evaluate the usability of the system The goal of this Phase IIb NHLBI Bridge application is to advance the simple automatic perfusion system developed in Phase I II to a commercial product for ECPR We will capture critical feedback from users and consolidate electronics to improve safety and usability The system will undergo complete verification and validation testing to prepare for regulatory submission In vivo studies will be performed to assess device functionality and durability At the end of Phase IIb we will have a highly integrated cardio pulmonary support system for use in ECPR with fully automated regulation of flow oxygen CO and temperature to support andquot controlled reperfusionandquot strategies while providing stable auto regulated perfusion We anticipate this APS device will lower the barriers for implementation of emergent ECPR and will result in expanded acceptance of these procedures resulting in greatly improved ECPR outcomes and greater availability of donor organs if resuscitation is not possible PUBLIC HEALTH RELEVANCE The goal of this Phase IIb NHLBI Bridge application is to advance the simple automatic perfusion system to a commercial product for ECPR and for in situ organ salvage after failed resuscitation The APS will make ECPR therapy safer simpler and less expensive and provide new capabilities to deliver controlled reperfusion that will minimize brain injury after prolonged cardiac arrest
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 195.58K | Year: 2012
DESCRIPTION (provided by applicant): This project will focus on the preparation and evaluation of nonthrombogenic, antibacterial nitric oxide (NO) releasing catheters. Phase 1 of this SBIR will: 1) develop unique NO secreting catheters (14-20 gauge); 2) test them in rabbit and sheep models to evaluate thrombogenicity and bacterial adherence; Phase 2 will scale up manufacturing and evaluate toxicity in preparation for human trials. The rationale for this research is to mimic the function of the endothelium.Low levels of NO released by the normal endothelium inhibit platelet adhesion and activation, thus preventing thrombus formation. Further, it has been shown that NO at low doses exhibits significant bactericidal activity. Hence, the preparation of catheters that secrete NO will solve two longstanding problems in the care of critically ill patients. The basic NO release polymer technology that employs novel diazeniumdiolate type NO donors has been developed in laboratories at the University of Michigan (U ofM) over the past 10 years. Successful applications of this technology have already included the development of anti-platelet coatings for extracorporeal circulation devices and the preparation more biocompatible implantable chemical sensors with improvedanalytical performance. Via collaboration with the research team at the U of M that has been working on this technology, MC3 now intends to develop and test catheters that release NO at controlled rates in order to prevent thrombosis and infection, two major problems associated with the use of catheters. PUBLIC HEALTH RELEVANCE: Clotting and infection is a major problem in intravascular (IV) catheters. Normal blood vessels secrete a chemical called nitric oxide which prevents these problems. This research will develop 14-20 gauge catheters which secrete nitric oxide, decreasing the risk of clotting and infection.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 220.03K | Year: 2012
DESCRIPTION (provided by applicant): Diabetic Retinopathy (DR), a vision threatening complication of diabetes, can be managed more effectively if detected early. We propose to enable such early diagnosis by developing a portable retinal imaging instrument- LSC EYE - that will, for the first time, extract both the anatomy and physiology of retinal microvasculature t high resolution without the need for dye administration. The LSC EYE is expected to cost less than 2000 and will enable primary care physicians to administer simple, quick and inexpensive retinal exams leading to timely diagnosis of DR. We have developed intellectual property central to the realization of such a device through two innovations: firstly, the extraction of retinal microvessel physiology using laser speckle contract imaging (LSCI) and secondly, the portable implementation of LSCI using a novel imaging sensor in conjunction with a miniaturized optical system. The imaging sensor has been custom designed and fabricated using complementary metal oxide semiconductor (CMOS) technology and performs on par with conventionally used imaging charge coupled device (CCD)cameras with respect to both sensitivity and noise. During Phase I, we will demonstrate the feasibility of achieving a portable retinal imager by incorporating a suite of novel image-enhancing algorithms into the LSCI technique and subsequently validate the safety and efficacy of the LSC EYE in a preclinical rabbit eye model. We will generate the first high resolution LSCI images ofthe retina capable of resolving blood vessels with diameters less than 60 m. Upon successful completion of Phase I milestones, we will embark on our Phase II efort during which we wil develop a clinical grade portable LSC EYE prototype, apply for investigational device exemption (IDE) and continue to undertake preliminary clinical investigation of the LSC EYE in small number of healthy volunteers and patients with advanced diabetes. ABSTRACT PUBLIC HEALTH RELEVANCE: There is a potential for earlydiagnosis of diabetic retinopathy through routine enhanced imaging of the retina. The goal of our project is to investigate the feasibility and develop laser contrast speckle imaging for high resolution imaging of retinal anatomy and physiology. We will develop a hand held prototype of a retinal imaging instrument with specifications, as might diagnose diabetic retinopathy early.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 971.23K | Year: 2011
DESCRIPTION (provided by applicant): Short bowel syndrome (SBS) represents a large loss of intestinal length, compromising the absorption of nutrients and fluids to sustain life. Although patients may be maintained on parenteral (intravenous) nutrition, the morbidity can be devastating and associated mortality rates exceed 30%. Care for each SBS patient is in excess of 250,000 per year and estimated costs for just the first five years of the care of a child with SBS exceed 1.5 million. Although a number ofstrategies have been used to treat SBS, the results have been disappointing with high complication rates and death. Application of longitudinal distractive forces, as directed with an intraluminally placed device, induces intestinal growth in pig small intestine (1.7-fold) over a 7-day period. The lengthening (enterogenesis) is not merely a stretching of the intestine, but true growth with preservation of intestinal function. The goal of this proposal is to develop a catheter-based device which could be placed intralumenally for days to weeks in a clinical setting to deliver longitudinal forces to the intestine, allowing for an elongation of the bowel while keeping the continuity of the gastrointestinal tract intact. The catheter enterogenesis device (CED)is envisioned as a simple, effective means of improving survival for SBS sufferers. Phase 1 resulted in the successful development of a working prototype. Two inflated balloons effectively anchored to the intestinal wall and delivered the forces previously determined to be effective for enterogenesis. The aims of this proposal is to develop the insertion and removal technique for the device with a preference for endoscopic placement, to assess the safety of the device through blood flow measurements, gross tissue examination and histological assessment and finally to demonstrate the efficacy of the device to lengthen the bowel in a chronic study. Device development will accompany each stage. The overall impact of this device will provide a low cost, safeand effective device to treat patients with short bowel syndrome in response to a tremendous unmet need for patients and their families. Variations of the CED may treat disease processes in other hollow visceral organs such as esophageal and intestinal atresia, ischemic and infection processes resulting in massive colon resection and congenital exstrophy. PUBLIC HEALTH RELEVANCE: The overall goal of this research proposal is to develop a catheter based device which will deliver linear forces resulting in the growth of the intestine. The catheter enterogenesis device (CED) is envisioned as a simple, minimally invasive and effective means of improving survival for short bowel syndrome sufferers.
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 1.26M | Year: 2014
DESCRIPTION provided by applicant This proposal involves the incorporation of a proprietary nitric oxide NO releasing polymer material NORL into a venous catheter to reduce infection and clotting Low levels of NO released by the normal endothelium inhibit platelet adhesion and activation thus preventing thrombus formation Further it has been shown that NO at low doses exhibits significant bactericidal activity Hence the preparation of catheters that secrete NO will solve two longstanding problems in the care of critically ill patients In Phase of this SBIR we developed a unique NO secreting polymer material that can release NO above physiological levels for up to days with minimal leaching of byproducts tested the materials for cytotoxicity and hemolysis and conducted testing in a sheep model to evaluate thrombogenicity and bacterial adherence We addressed handling and packaging requirements to maintain efficacy of the materials Based on the cost of materials and the specialized handling requirements we identified a product that would benefit from the prolonged protection offered by the material and that has a high enough sale price to tolerate the increased handling expenses This Phase II application is targeted at building out the manufacturing process found to be most effective for incorporating NORL in the catheter performing extensive preclinical assessments and evaluating the coating in vivo for anti microbial and anti platelet properties The initial target product for NORL will be a dual lumen catheter DLC suitable for adult extracorporeal membrane oxygenation ECMO Specifically we will construct a device for automated and controlled fabrication of the NORL catheter and conduct design verification of the NORL loaded catheter We will also work with our collaborators at the University of Michigan to perform extensive in vivo evaluations of the new NO release catheter At the conclusion of Phase II we will be prepared to transfer the developed process and equipment to a contract manufacturer This approach is a significant advance in improving the biocompatibility and anti microbial features of intravascular catheters since it utilizes chemistry that exactly mimics endogenous NO release function in our bodies including from endothelial cells to inhibit platelet adhesion activation and by various immune cells e g macrophages neutrophils etc to kill bacteria By decreasing both clotting and infection this technology will simultaneously increase catheter longevity and decrease patient morbidity and costs PUBLIC HEALTH RELEVANCE Clotting and infection is a major problem in intravascular IV catheters Normal blood vessels secrete a chemical called nitric oxide which prevents these problems This research will develop an ECMO Dual Lumen Catheter that secretes nitric oxide decreasing the risk of clotting and infection
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 1.19M | Year: 2011
DESCRIPTION (provided by applicant): Heart valve regurgitation is a serious condition related to heart disease. The most common and effective surgical method for treating this disease is with the use of an annuloplasty ring, which reduces the size of a dilated valve annulus to restore normal function. Many patients do not receive this procedure, however, either because they are too sick to undergo open heart surgery, or their condition has not yet progressed to the point at which surgery is justified. To address this large untreated patient population, many efforts have been undertaken to develop technology to repair leaky valves via catheter. Of these, the Millipede concept is the only device which can perform a true ring annuloplasty. This concept uses a ring that can both expand and contract under a radial force and has many small barbed anchors around its perimeter. After implant, a novel locking mechanism holds the ring at the desired diameter. The implantation process is performed by first inserting thedelivery tool, an oversized wire basket , into the annulus. This wire basket is larger than the annulus in diameter, but flexible enough to conform to the annular dimensions, which allows the user to find the annular tissue regardless of the size or shape of the annulus. Once placed in the annulus, the wires provide a series of rails, or delivery paths, over which the ring is delivered. The result is an automatic alignment of the ring and the annulus. Once aligned, a simple forward push of the ring drives the barbed anchors into the tissue and secures the ring in place. The basket is then contracted down and removed. In Phase II of this project we will surgically implant the prototypes developed in Phase I in animals. After developing a fully functionaldelivery system and conducting in vitro durability testing on the ring, we will perform percutaneous implants in animals. PUBLIC HEALTH RELEVANCE: The goal of this project is to develop a sutureless annuloplasty ring for the treatment of dilated, leaking heart valves. This will lead to an annuloplasty ring that can be implanted without surgery, which will benefit a significant number of patients who have valve disease but are not candidates for surgery.
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 209.54K | Year: 2016
ABSTRACT Extracorporeal membrane oxygenation ECMO use continues to increase as a supportive measure for cardio respiratory failure Pediatric patients with severe acute left ventricular LV systolic dysfunction are often supported with venoarterial VA ECMO as a short term bridge to recovery transplant or a ventricular assist device VAD Although this often provides the much needed temporary gas exchange and increase in cardiac output to all important end organs lack of egress of blood from the LV can lead to over distension and elevated LV end diastolic pressure LVEDP which reduces myocardial oxygen delivery and recovery The risk of progressive increase in left sided filling pressures needs to be monitored closely to avoid the deleterious effects of left heart distention Left ventricular distention in patients with profoundly reduced left ventricular contractility is a major risk factor for poor myocardial recovery and failure to wean from ECMO Mechanical decompression of the left heart during ECMO is sometimes required to address ventricular distention and is often a life saving intervention For patients who do not have open access to the heart for surgical decompression i e post operative cardiac patients left ventricular decompression is most commonly accomplished by percutaneous transseptal puncture followed by either septostomy or placement of a drain or device to keep the atrial communication patent Due to the lack of a FDA approved devices for this indication all options of decompression represent off label use of devices not specifically designed for this intervention The goal of this project is to design test and produce a line of pediatric and adult ventricular assist catheters VAC that can be used for short term left heart decompression in patients on VA ECMO for acute severe LV systolic dysfunction The MC VAC line will include lengths and diameters to cover the entire spectrum of sizes required for the pediatric population for both low flow left heart decompression and high flow total ventricular assist The largest size catheters will also support the adult patient so the line will be designed to truly match the entire patient spectrum Phase I of the study will include capturing detailed design inputs for the population by analyzing pediatric patient data from clinical cases at The University of Michigan User requirements will be translated into design inputs outputs by MC andapos s team of experienced cannula design engineers who have designed several commercially successful cannula and introducer systems Feasibility will be established by evaluating performance of the VAC against specific criteria unique to usage in the pediatric application Phase II funding if granted will be sufficient to complete verification validation testing transfer to manufacture and FDA and CE mark submissions We have assembled a synergistic team of experts clinicians marketers manufacturers and engineers who are uniquely qualified to carry out the proposed work NARRATIVE Extracorporeal Membrane Oxygenation ECMO has become a widely accepted means to provide short term circulatory support for pediatric and adult patients suffering from acute cardiac failure The biggest problem for cardiac ECMO is that complications can arise when pressure builds in the heart and unloading or decompression of the left side is frequently required The goal of this project is to develop a pediatric and adult line of cardiac catheters that can be used to decompress the left heart in patients on ECMO as well as a full circulatory assist catheter device if indicated Currently there is no such catheter solely approved for this use in pediatrics and options are limited for adults
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 149.69K | Year: 2012
DESCRIPTION (provided by applicant): Dentin hypersensitivity (DH) is a common problem and the treatment modalities are, if they work at all, short lived. The object of this project is t produce a product that can occlude patent dentinal tubules (the causeof DH) and adhere to the wet interior surface of the dentinal tubules. The research goal of this study is to optimize the fluorapatite (FA) crystal/polymer of adhesive polymer, poly(DMA-MEA) ratio for immediate and long term occlusion of the patent dentinal tubules. The FA crystals are the same as those found in dental enamel and synthetic polymer which mimics the naked amino acid 3,4 dihydroxyphenylalanine (DOPA) found in the mussel adhesive mucus. The synthesized FA crystals will be mixed with the polymer at certain ratios, applied to dentin sections and the dentinal conductivity (the gold standard used for testing dentin desensitizing agents) measured. . Once the optimized ratio for occlusion has been established its effect on dentinal tubule occlusion will be observed in the SEM . The release of F, Ca and PO4 from the FA/polymer paste will also be measured at neutral and acidic pH. This ion release, along with saliva, will help in the formation of a mineralized layer on the dentin which will help in thelong term relief f DH. This product for treating DH will be: biocompatible, non-toxic, allow for diffusion of ions; easily applied; adherent to tooth structure in the wet environment of the oral cavity; and aesthetic - a natural product. PUBLIC HEALTH RELEVANCE: This grant proposes a novel way of treating sensitive teeth; a problem that affects about 50% of the population at sometime. A desensitizing paste will be produced which contains mineral crystals which are similar to the natural crystals in teeth, mixed with a gel that will stick to wet tooth surfaces. It is anticipated that the paste will give immedite relief by blocking open tubules running from the surface of the dentin to the live part of the toot; and long term relief by causing amineralized barrier to form, overtime, on the sensitive tooth surface.