Harvard-MIT Division of Health Sciences and Technology

hst.mit.edu
Cambridge, MA, United States

Founded in 1970, the Harvard–MIT Division of Health science and Technology, or HST, is one of the oldest and largest biomedical engineering and physician-scientist training programs in the United States and the longest-standing functional collaboration between Harvard University and the Massachusetts Institute of Technology .HST's unique interdisciplinary educational program brings engineering as well as the physical and biological science from the scientist's bench to the patient's bedside. Conversely, it brings clinical insight from the patient's bedside to the laboratory bench. In this way, HST students are trained to have deep understanding of engineering, physical science, and the biological science, complemented with hands-on experience in the clinic or in industry; and they become conversant with the underlying quantitative and molecular aspects of medicine and biomedical science. Within the division, more than 400 graduate students work with eminent faculty and affiliated faculty members from throughout the MIT and Harvard communities. HST is also the home of the Laboratory of Computational Physiology which hosts the MIMIC II database and PhysioNet.In addition to its outstanding record of accomplishment for research in human health care, HST educational programs are distinguished by three key elements: A strong quantitative orientation Required hands-on experience in a clinical or industry setting A focused interdisciplinary research project↑ Wikipedia.

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News Article | April 27, 2017
Site: www.eurekalert.org

Imagers, gastric pacemakers and other diagnostic and therapeutic tools could someday transform the way diseases of the gastrointestinal tract are measured and treated. But in order for these electronic devices to work, they need a power source. Traditional power sources, such as batteries, can be incompatible with the mucosal lining of the gastrointestinal tract and have a limited lifespan within the body. A more promising possibility is to power electronic devices from outside the body. In a new study published in Scientific Reports, investigators from Brigham and Women's Hospital, Massachusetts Institute of Technology and The Charles Stark Draper Laboratory report that an ingestible electronic capsule, complete with a capsule-sized antenna capable of receiving a radio signal wirelessly, can safely power a device in the gastrointestinal tract in preclinical models. The new work makes wireless medical electronics for treating the gastrointestinal tract one step closer to reality. "Electronic devices that can be placed in the gastrointestinal tract for prolonged periods of time have the potential to transform how we evaluate and treat patients. This work describes the first example of remote, wireless transfer of power to a system in the stomach in a large preclinical animal model -- a critical step toward bringing these devices into the clinic," said co-corresponding author Carlo "Gio" Traverso, MD, PhD, a gastroenterologist and biomedical engineer at BWH. Other medical devices -- such as cochlear implants or neural probes - use a well-established technique known as near-field coupling to deliver power wirelessly. But ingestible devices must be small enough to be swallowed and, moreover, lie a significant distance from the surface of the body, making this technique unattainable for most gastrointestinal electronics. A new technique known as mid-field coupling provides an alternative way to deliver power to deeply implanted devices. Mid-field coupling operates at higher frequencies to deliver power two to three times more efficiently. To test whether mid-field coupling could help deliver power from outside the body into the gastrointestinal tract, the research team designed antennas capable of operating efficiently in tissue. They then placed one antenna outside of the body and the other in the esophagus, stomach and colon of a swine model. They were able to transmit power levels of 37.5 uW, 123 uW and 173 uW, respectively, all of which are sufficient to wirelessly power a range of medical devices from outside of the body. "We are very excited about this work which we feel can someday offer many new opportunities for oral drug delivery of different molecules," said co-corresponding author Robert Langer, Institute Professor from the Harvard-MIT Division of Health Sciences and Technology. "In further work, we would like to expand on these measurements by characterizing the effects of animal size, antenna depth, orientation and more on transmission efficiency, and focus on propagating fields - or the way power travels - to make transmission even more efficient," said Traverso. This work was made possible in part through funding from the National Institutes of Health and a Draper Fellowship. The authors declare no competing financial interests or other interests that might be perceived to influence the results and/or discussion reported in this article.


WALTHAM, Mass.--(BUSINESS WIRE)--NeuroMetrix, Inc. (Nasdaq: NURO) reported today that Notices of Allowance has been issued for patents covering key technological features of the Company’s Quell® Wearable Pain Relief Technology™ by the European Patent Office, the Japan Patent Office, and the State Intellectual Property Office of the People's Republic of China. The allowed patent claims address an essential element in the Company’s proprietary technology that automatically controls nerve stimulation to optimize pain relief. In particular, the patent covers a novel calibration procedure that customizes nerve stimulation for each Quell user. In addition, the allowed patent claims protect the unique integrated Quell design that combines a neurostimulator, an electrode array, and an accelerometer. This technology enables automatic adjustment of nerve stimulation based on the user’s position and movement, with applications such as optimizing therapy during sleep. The Company expects the three patents to formally issue by the third quarter of 2017. “We are pleased to have received these important Notice of Allowances for the Quell technology in the European Union, Japan and China. These are the three key expansion markets for the Quell business,” said Shai N. Gozani, M.D., Ph.D., President and CEO of NeuroMetrix. "We are currently in discussions with strategic partners about licensing or distributing Quell outside our core North American market. These patent claim allowances may help advance these discussions towards formal agreements.” About Quell Quell is designed for millions of people suffering from chronic pain. The advanced wearable device is lightweight and can be worn during the day while active, and at night while sleeping. It has been cleared by the FDA for treatment of chronic pain without a prescription. In a recent study, 81% of Quell users reported an improvement in their chronic pain. Quell users can personalize and manage therapy discreetly via the Quell Relief app. Quell also offers advanced health tracking relevant to chronic pain sufferers including pain, sleep, activity, and gait. Quell was the winner of the 2016 SXSW (South by Southwest) Innovation Award for Best Wearable Technology. Quell is available at select healthcare professionals and retailers. Visit QuellRelief.com for more information. About NeuroMetrix NeuroMetrix is a commercial stage, innovation driven healthcare company combining bioelectrical and digital medicine to address chronic health conditions including chronic pain, sleep disorders, and diabetes. The company's lead product is Quell, an over-the-counter wearable therapeutic device for chronic pain. Quell is integrated into a digital health platform that helps patients optimize their therapy and decrease the impact of chronic pain on their quality of life. The company also markets DPNCheck®, a rapid point-of-care test for diabetic neuropathy, which is the most common long-term complication of Type 2 diabetes. The company maintains an active research effort and has several pipeline programs. The company is located in Waltham, Massachusetts and was founded as a spinoff from the Harvard-MIT Division of Health Sciences and Technology in 1996. For more information, please visit NeuroMetrix.com.


News Article | May 5, 2017
Site: www.businesswire.com

WALTHAM, Mass.--(BUSINESS WIRE)--NeuroMetrix, Inc. (Nasdaq: NURO) held its first Quell® Wearable Pain Relief Technology™ user event last Thursday, April 27. As a customer-focused company, NeuroMetrix frequently looks to its users to inform product updates and innovation. NeuroMetrix welcomed a group of 30 Quell users to its Waltham headquarters to “meet the makers,” learn about upcoming Quell product features, share their stories, and give feedback on the product. Quell users learned about product development directly from Shai N. Gozani, M.D., Ph.D., President and CEO at NeuroMetrix, and connected with peers and NeuroMetrix’s customer care, engineering, and marketing teams. “We know that Governor Baker’s goal is to establish Massachusetts as a digital health hub and we are proud to contribute to that mission as a Massachusetts-based digital health company,” said Frank McGillin, Senior Vice President and Chief Commercial Officer at NeuroMetrix. “Many of those living with chronic pain in the Commonwealth have been reliant on medication to manage their day-to-day pain. Hearing that Quell has enabled many of the event’s attendees to reduce or eliminate their use of opioids was a rewarding experience. We look forward to hosting more of these events in the future.” Attendees had the opportunity to share their experiences and discuss how Quell has changed their approach to pain management. "I did not know what it was like to live life without pain, until I got my Quell,” said one attendee. Another Quell user stated, “Quell has returned my freedom to choose what I want to do daily, not what my pain will let me do today. I have my life back again!" While Quell provides an opportunity to reduce drug reliance, the reality is that many chronic pain sufferers will require some degree of continued usage of medications to deal with their pain. NeuroMetrix believes a “treatment toolbox” approach that looks to supplement pain medications with technology and other alternatives may be effective in many cases. “There is no one-size-fits-all approach to treating chronic pain. Our goal is to provide a drug free treatment option to enhance the quality of life for those living with chronic pain,” said Dr. Gozani. “As a consumer health company, engaging our users is critical to achieving this goal. We were impressed by the response we received and will be applying this feedback to continue improving our product.” About Quell Quell is designed for millions of people suffering from chronic pain. The advanced wearable device is lightweight and can be worn during the day while active, and at night while sleeping. It has been cleared by the FDA for treatment of chronic pain without a prescription. In a recent study, 81% of Quell users reported an improvement in their chronic pain. Quell users can personalize and manage therapy discreetly via the Quell Relief app. Quell also offers advanced health tracking relevant to chronic pain sufferers including pain, sleep, activity, and gait. Quell was the winner of the 2016 SXSW (South by Southwest) Innovation Award for Best Wearable Technology. Quell is available at select healthcare professionals and retailers. Visit QuellRelief.com for more information. About NeuroMetrix NeuroMetrix is a commercial stage, innovation driven healthcare company combining bioelectrical and digital medicine to address chronic health conditions including chronic pain, sleep disorders, and diabetes. The company's lead product is Quell, an over-the-counter wearable therapeutic device for chronic pain. Quell is integrated into a digital health platform that helps patients optimize their therapy and decrease the impact of chronic pain on their quality of life. The company also markets DPNCheck®, a rapid point-of-care test for diabetic neuropathy, which is the most common long-term complication of Type 2 diabetes. The company maintains an active research effort and has several pipeline programs. The company is located in Waltham, Massachusetts and was founded as a spinoff from the Harvard-MIT Division of Health Sciences and Technology in 1996. For more information, please visit NeuroMetrix.com.


News Article | April 17, 2017
Site: www.eurekalert.org

Multiple myeloma is a cancer of the plasma cells, which are white blood cells produced in bone marrow that churn out antibodies to help fight infection. When plasma cells become cancerous, they produce abnormal proteins, and the cells can build up in bone marrow, ultimately seeping into the bloodstream. The disease is typically diagnosed through a bone marrow biopsy, in which a needle is inserted near a patient's hip bone to suck out a sample of bone marrow -- a painful process for many patients. Clinicians can then isolate and analyze the plasma cells in the bone marrow sample to determine if they are cancerous. There is currently no way to easily detect plasma cells that have escaped into the bloodstream. Circulating plasma cells are not normally found in healthy people, and the ability to detect these cells in blood could enable doctors to diagnose and track the progression of multiple myeloma. Now engineers at MIT have devised a microfluidic technique to capture and count circulating plasma cells from small samples of blood. The technique, which relies on conventional blood draws, may provide patients with a less painful test for multiple myeloma. "Procedures of the traditional tissue biopsy are painful, associated with complications such as potential infections, and often available only in central hospitals which require patients to travel long distances," says former MIT postdoc Mohammad Qasaimeh. "Capturing plasma cells from blood samples can serve as a liquid biopsy, which can be performed in clinics as often as required, and serve as a diagnostic and prognostic test during and after chemotherapy treatment. Moreover, captured cells can be used for drug testing and thus serve as a tool for personalized medicine." Qasaimeh and his colleagues have published their results today in the journal Scientific Reports. His co-authors include Rohit Karnik, an associate professor in MIT's Department of Mechanical Engineering; Yichao Wu and Suman Bose, both former students; Jeffrey Karp, an associate professor in the Harvard-MIT Division of Health Sciences and Technology; and Rao Prabhala, an instructor in medicine at Dana-Farber Cancer Institute and Harvard Medical School. The group's technique builds on a microfluidic design that was previously developed by George Whitesides, a professor of chemistry at Harvard University. Whitesides and his colleagues fabricated a small microchip, the channel of which they etched with repeating, V-shaped grooves, similar to a herringbone pattern. The grooves cause any fluid flowing through the microchip to swirl about in eddies, rather passing straight through. The cells within the fluid therefore have a higher chance of making contact with the floor of the device, as first shown by Memhmet Toner at Massachusetts General Hospital. Researchers including Karnik have since reproduced this microfluidic design, coating the microchip's floor with certain molecules to attract cells of interest. In its latest work, Karnik's team used the microfluidic herringbone design to capture circulating plasma cells. They coated the channels of a microchip, about the size of a glass slide, with CD138, an antibody that is also expressed on the membranes of plasma cells. The team then flowed small, 1-milliliter samples of blood through the device. The herringbone grooves circulated the blood in the microfluidic channels, where the antibodies, acting as tiny Velcro pads, grabbed onto any passing plasma cells while letting the rest of the blood flow out of the device. Once the cells were isolated in the microchip, the researchers could count the cells, as well determine the kinds of antibodies that each cell secretes. "With the ease of a blood draw" The researchers tested the device using blood samples from healthy donors as well as patients with the disease. After counting the number of cells captured in each sample, they observed very low numbers of circulating plasma cells in healthy samples -- about two to five cells per milliliter of blood -- versus substantially higher counts in patients diagnosed with multiple myeloma, of about 45 to 184 cells per milliliter. The team also analyzed the captured plasma cells to determine the type of antibodies they produced. Plasma cells can generate one of two kinds of antibodies, known as kappa- and lambda-type. In addition to conducting bone marrow biopsies, clinicians can analyze blood samples for the ratio of these two antibodies, which can be an indicator of how the disease is progressing. Karnik and his colleagues determined the ratio of plasma cells producing kappa- and lambda-type antibodies, and compared them to conventional blood tests for the same antibodies, for both healthy subjects and patients with multiple myeloma. Encouragingly, they found both sets of results matched, validating the microfluidic device's accuracy. Surprisingly, the team noted that patients who were in remission exhibited higher counts of circulating plasma cells than healthy donors. These same patients had shown normal ratios of antibodies in conventional blood tests. Karnik says that the group's new device may reveal more subtle information about a patient's state, even in remission. "When patients go into remission, their antibody levels can look normal," Karnik says. "But we detect a level of circulating plasma cells that is above the baseline. It's hard to tell whether these cells are cancerous, but at least this technique is giving us more information. With the ease of a blood draw, this may enable us to track cancer in a much better way." Karnik adds that in the future, researchers may use the group's design to perform genetic tests on the captured cells, or to look for mutations in the cells that may further characterize the disease. "We can capture and stain these cells in the device, which opens the possibility of studying whether there are new mutations in the cells," Karnik says. "With cancers like multiple myeloma, even for patients in remission, cancer can recur. Detecting the level or mutation of plasma cells in blood might provide an early detection method for these patients." This research was supported, in part, by the National Institutes of Health and the Al Jalila Foundation.


Greenberg S.A.,Harvard-MIT Division of Health Sciences and Technology
Muscle and Nerve | Year: 2014

Introduction: Recent studies have identified circulating immunoglobulin (Ig) G autoantibodies against cytoplasmic 5′-nucleotidase 1A (cN1A; NT5C1A) in patients with inclusion body myositis (IBM), whose detection provides for an IBM blood diagnostic test. Whether or not anti-cN1A autoantibody isotypes other than IgG are present in IBM has not previously been reported. Methods: Plasma and serum samples from 205 patients (50 with and155 without IBM) were studied for the presence of IgM and IgA, in addition to IgG, anti-cN1A autoantibodies using immunoblots and enzyme-linked immunoassays (ELISAs). Results: IgM, IgA, and IgG anti-cN1A autoantibodies were detected by ELISA with similar sensitivities (49-53%) and specificities (94-96%), but with differing patterns of autoantibody isotype presence. Combination assays of all 3 autoantibody levels improved diagnostic sensitivity to 76%. Conclusions: In addition to previously recognized IgG anti-cN1A autoantibodies, IBM patients have circulating IgM and IgA anti-cN1A autoantibodies. Differing patterns of these isotypes may be present and useful for diagnosis. © 2014 Wiley Periodicals, Inc.


Mirny L.A.,Harvard-MIT Division of Health Sciences and Technology
Proceedings of the National Academy of Sciences of the United States of America | Year: 2010

Cooperative binding of transcription factors (TFs) to promoters and other regulatory regions is essential for precise gene expression. The classical model of cooperativity requires direct interactions between TFs, thus constraining the arrangement of TF sites in regulatory regions. Recent genomic and functional studies, however, demonstrate a great deal of flexibility in such arrangements with variable distances, numbers of sites, and identities of TF sites located in cis-regulatory regions. Such flexibility is inconsistent with cooperativity by direct interactions between TFs. Here, we demonstrate that strong cooperativity among noninteracting TFs can be achieved by their competition with nucleosomes. We find that the mechanism of nucleosome-mediated cooperativity is analogous to cooperativity in another multimolecular complex: hemoglobin. This surprising analogy provides deep insights, with parallels between the heterotropic regulation of hemoglobin (e.g., the Bohr effect) and the roles of nucleosome-positioning sequences and chromatin modifications in gene expression. Nucleosome-mediated cooperativity is consistent with several experimental studies, is equally applicable to repressors and activators, allows substantial flexibility in and modularity of regulatory regions, and provides a rationale for a broad range of genomic and evolutionary observations. Striking parallels between cooperativity in hemoglobin and in transcriptional regulation point to a general mechanism that can be used in various biological systems.


Qi H.,Harvard-MIT Division of Health Sciences and Technology
Nature communications | Year: 2013

Using DNA as programmable, sequence-specific 'glues', shape-controlled hydrogel units are self-assembled into prescribed structures. Here we report that aggregates are produced using hydrogel cubes with edge lengths ranging from 30 μm to 1 mm, demonstrating assembly across scales. In a simple one-pot agitation reaction, 25 dimers are constructed in parallel from 50 distinct hydrogel cube species, demonstrating highly multiplexed assembly. Using hydrogel cuboids displaying face-specific DNA glues, diverse structures are achieved in aqueous and in interfacial agitation systems. These include dimers, extended chains and open network structures in an aqueous system, and dimers, chains of fixed length, T-junctions and square shapes in the interfacial system, demonstrating the versatility of the assembly system.


Mirny L.A.,Harvard-MIT Division of Health Sciences and Technology
Chromosome Research | Year: 2011

The fractal globule is a compact polymer state that emerges during polymer condensation as a result of topological constraints which prevent one region of the chain from passing across another one. This long-lived intermediate state was introduced in 1988 (Grosberg et al. 1988) and has not been observed in experiments or simulations until recently (Lieberman-Aiden et al. 2009). Recent characterization of human chromatin using a novel chromosome conformational capture technique brought the fractal globule into the spotlight as a structural model of human chromosome on the scale of up to 10 Mb (Lieberman-Aiden et al. 2009). Here, we present the concept of the fractal globule, comparing it to other states of a polymer and focusing on its properties relevant for the biophysics of chromatin. We then discuss properties of the fractal globule that make it an attractive model for chromatin organization inside a cell. Next, we connect the fractal globule to recent studies that emphasize topological constraints as a primary factor driving formation of chromosomal territories. We discuss how theoretical predictions, made on the basis of the fractal globule model, can be tested experimentally. Finally, we discuss whether fractal globule architecture can be relevant for chromatin packing in other organisms such as yeast and bacteria. © 2011 The Author(s).


Li L.,Harvard-MIT Division of Health Sciences and Technology
Lab on a chip | Year: 2012

In the stomach, a layer of gastric mucus protects the epithelial cells of the stomach wall against damage by the acidic digestive juices in the gastric lumen. Despite considerable research, the biophysical mechanisms for this acid barrier are not understood. We present an in vitro microfluidic tool to characterize the stomach acid barrier, in which purified mucin polymers are "secreted" against an acidic zone on chip, mimicking the in vivo secretion of gastric mucus into an acidic stomach lumen. This device reconstitutes both the H(+) concentration gradient and outward flow environment of the mucus layer in vivo. Our experiments demonstrate that a continuously secreted mucin layer hinders acid diffusion, suggesting novel insights into the barrier role of mucins. More broadly, our system may serve as a platform tool for studying the barrier functions provided by mucus layers in the body and for studying mucus drug interactions.


Ghaffari R.,Harvard-MIT Division of Health Sciences and Technology
Nature communications | Year: 2010

Remarkable sensitivity and exquisite frequency selectivity are hallmarks of mammalian hearing, but their underlying mechanisms remain unclear. Cochlear insults and hearing disorders that decrease sensitivity also tend to broaden tuning, suggesting that these properties are linked. However, a recently developed mouse model of genetically altered hearing (Tectb(-/-)) shows decreased sensitivity and sharper frequency selectivity. In this paper, we show that the Tectb mutation reduces the spatial extent and propagation velocity of tectorial membrane (TM) travelling waves and that these changes in wave propagation are likely to account for all of the hearing abnormalities associated with the mutation. By reducing the spatial extent of TM waves, the Tectb mutation decreases the spread of excitation and thereby increases frequency selectivity. Furthermore, the change in TM wave velocity reduces the number of hair cells that effectively couple energy to the basilar membrane, which reduces sensitivity. These results highlight the importance of TM waves in hearing.

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