The third round of BMEidea competition winners featured technologies with the potential to revolutionize how we deliver vaccines, how we treat Parkinson's disease and how we repair peripheral nerve injuries. We caught up with the teams a year and a half after the competition to see what they were up to, how their projects were going, and how participating in the BMEidea competition influenced their careers.
First prize: Rotavirus Vaccination via Oral Thin Film Delivery, Johns Hopkins University
A big part of innovation is thinking about problems in a different way. Changing your point of reference can lead to creativity, and creativity can lead to originality.
An example is the Rotavirus Vaccination team from Johns Hopkins University, winner of the 2007 BMEidea competition. Rotavirus, a disease that causes severe diarrhea and vomiting in children, kills 600,000 people in the developing world each year. While there is a vaccine for the disease, few children in the developing world end up getting it due to problems with cold chain storage: the vaccine has to be kept refrigerated, often an impossibility in rural areas where refrigeration is scarce.
The innovative solution? Change the vaccine itself. While the liquid form of rotavirus vaccine requires refrigeration, the Johns Hopkins team is developing a dry form derived from thin film technology, similar to Listerine's quick-dissolving breath strips. The team's dissolvable strip is seeded with the vaccine, then coated with a special material to protect it in the child's stomach. That same coating disintegrates in the small intestine, releasing the vaccine, triggering an immune response and preventing future infection. All on a little strip that requires no refrigeration and is light and easy to ship.
The Rotavirus project began at Aridis Pharmaceuticals, a San Jose firm that invented a rotavirus vaccine stable at room temperatures. Aridis approached Johns Hopkins professor Hai-Quan Mao about coming up with a drug delivery vehicle for its novel vaccine. Mao brought the challenge to one of his undergraduate lab assistants, Chris Yu, who became co-leader of the team that tackled the project.
They faced several obstacles right out of the chute. For one, they couldn't copy the manufacturing process that Listerine uses to make breath strips, since the harsh solvents and high temperatures it requires ended up destroying the live vaccine. They also had to devise a protective coating that would remain intact when exposed to stomach acid but dissolve in the small intestine. Said Yu, "Our technology is geared toward delivering a live attenuated virus for a vaccine, not just freshening breath. We quickly found out that in order to get it to work, we'd need to take a different approach--use more advanced technology.
They got through the challenges with hard work and research. They developed a room-temperature production and drying process to fabricate the strips and identified an FDA-approved biocompatible polymer coating that would protect the vaccine in the stomach and release it in the small intestine.
Much more work remains before the vaccine is a finished product, however. Since winning BMEidea funding the team has continued research. And while most of the team has graduated and moved on, Yu is remaining on the project while pursuing his masters at Johns Hopkins. "Aridis is still very interested in the product, of course," said Yu. "They're very happy with our progress, and have hired a post-doc to work with me in the lab."
"The foundation of the system has already been laid: how we're going to deliver the vaccine to the small intestine, what kind of release profile it will have. Now we need to optimize the system. We need to optimize the film formulation, and ultimately add as many components as possible to make it easy to ship and make sure it's easy to use for inexperienced healthcare providers."
Yu is honest about the biggest benefit of winning the BMEidea competition: the money helps. "NCIIA has given us a lot of the financial backing for what we're doing. A lot of the components that are needed to formulate and test our design are actually quite expensive. We wouldn't be as far along as we are without the funding."
Beyond that, Yu says that participating in BMEidea gave him a better grasp of the business issues surrounding rotavirus. "Even though the rotavirus vaccine is abundant in the US, virtually none of it is making it to developing countries that need it," he said. "Science aside, the business end of this project--getting the vaccine into the hands of people who need it--is extremely important and will need to be addressed as soon as our prototype is ready to go."
Second prize: enLight: Enabling Life with Light, Stanford University
Parkinson's disease is a degenerative central nervous system disorder that causes a breakdown in muscle function and speech. The disease affects 1.5 million patients in the US alone--a number that will likely rise as the population ages--yet there remains no definitive treatment for PD. Current therapies run the gamut from drugs to surgery all the way to qigong, a traditional Chinese breathing exercise.
One of the most promising new approaches to treating PD is deep brain stimulation (DBS). Since a main factor involved in causing Parkinson's is the insufficient formation and action of dopamine, DBS involves placing an electrode deep within the brain to stimulate the parts of the brain responsible for dopamine production. DBS has been shown to alleviate some of the motor tremors in Parkinson's patients and can lead to an improvement in quality of life.
The drawback? DBS is only effective in a very small percentage of PD patients (~5%) because electrode-based stimulation is highly nonspecific. During DBS, many more brain cells other than those responsible for PD pathology are stimulated, which can lead to a number of severe side effects including apathy, hallucinations, compulsive gambling, hypersexuality, cognitive dysfunction and depression. Clearly there is a need for a better device--one that can specifically target only the neurons involved in PD, lessening the side effects.
This Stanford University team, winner of second place in the 2007 BMEidea competition, believes it's found the solution. The team is developing enLight, a remarkably forward-thinking, novel treatment for PD that enables the effective and reliable control of neural activity using light.
Here's how it works: instead of implanting an electrode, the team implants a thin optic fiber in the brain. Then, using gene therapy techniques, they introduce a genetically coded protein that makes the neurons specifically involved in Parkinson's sensitive to light. The optic fiber shines light into the right region of the brain, and voila, only the neurons associated with Parkinson's are activated. The ability to directly and specifically control neurons represents a major step forward and has the potential to revolutionize the field.
It all started with algae--or, more specifically, the algae-related lab work of Feng Zhang, a graduate student at Stanford. "When I first joined the lab in January 2005," says Zhang, "I started working on technology that would allow you to take protein from green algae and transfer it to neurons to make them light sensitive. Algae have light-sensitive neurons that they use to find sunlight for photosynthesis; by transferring this algal protein into animal neurons we figured we would be able to very precisely control neural firing."
Zhang was right. After establishing the validity of the technology, his team started developing genetic techniques that would allow them introduce the protein into specific neurons. They do this through lentiviruses, a genus of viruses that can deliver a significant amount of genetic information into the DNA of a host cell. Thus the biological basis of the technology was formed.
Soon enough they began to think about ways to use the technology for therapeutic purposes, and hit upon Parkinson's as the most likely first target. "We looked into diseases that could be treated using our approach, and, largely because of the body of research that has already been formed on Parkinson's and deep brain stimulation, we chose Parkinson's."
The team has made solid progress since winning BMEidea funding, filing several patents and moving toward pre-clinical animal testing. According to Zhang, the next steps are getting the biological reagent produced and ramping up to clinical trials. On the device side, refinements need to be made to the optical fiber "to make sure we're bringing in enough light, but not too much light. It's a tough technical challenge."
Other challenges involve finding the right animal model to use for testing, and making sure their virus doesn't cause damage to the brain--that it infects the right neurons. But despite all the obstacles to overcome, Zhang sees this product hitting the market in five to eight years, and making a big impact.
As far as the impact of winning BMEidea is concerned, Zhang strikes a familiar chord: winning gave his project credibility. "First of all it gave us validation--maybe our idea isn't so crazy after all!" he said. "Plus the events that we've attended as a result of winning BMEidea have been very helpful. I've been able to network with people who work in the medical device industry and gotten insight on basic things, like how to think about medical devices, how to manufacture a device, etc. They were very helpful."
Third prize: Bioactive Nanopatterned Grafts for Nerve Regeneration, University of California, Berkeley
Peripheral nerves are the extensive network of nerves outside the brain and spinal cord. Like static on a telephone line, peripheral nerve injuries distort or interrupt the messages between the brain and the rest of the body, affecting a person's ability to move or feel normal sensations. This is a common problem affecting about 800,000 Americans each year.
The gold standard approach to fixing it is the nerve autograft--removing a segment of nerve from one part of the body and suturing it in place at the site of injury. While this is effective in some cases, the approach comes with a number of risks and drawbacks: the donor nerves tend to be small, usually requiring the doctor to stack a bunch of them together to make an implantable graft; two invasive surgeries are required, one for harvesting the donor nerves and one for implanting them; sometimes the graft simply doesn't work; some patients don't have any nerves suitable for donation; and the donor site can react badly, causing more pain than the nerve injury itself.
A different approach to the problem gaining in popularity is the world of synthetic grafts. Made of various polymers wrapped into a sturdy tube shape, a handful of grafts are currently on the market. But the current designs come with limitations as well: none can outperform the nerve autograft in clinical trials, they don't provide cues for regeneration the way a normal nerve would, and they can't bridge gaps longer than four centimeters. There is a clinical need for a synthetic graft that better mimics the nerve autograft and has the ability to regenerate damaged nerves of all sizes, and this UC Berkeley team is looking to provide it.
The team, winner of third place in the 2007 BMEidea competition and now incorporated as NanoNerve, is developing a novel synthetic graft that enhances and guides nerve regeneration across a range of peripheral nerve injuries. The tubular graft is composed entirely of nanoscale polymer fibers loaded with bioactive molecules that provide growth cues for regenerating. The technology is also capable of spanning large gaps.
Altogether, this makes a product that is "simply better than what's out there," according to team leader Shyam Patel. "We can heal longer nerve injuries, we can provide growth cues, and we'll be proving that through human trials taking place next year."
The key to the technology has to do with how the grafts are fabricated. The most common method of fabricating polymer nanofibers is to use an electrical field to "spin" very thin fibers. This technique, called electrospinning, can be used to make nanofiber scaffolds in various shapes. The key innovation allows the team to fabricate grafts composed entirely of nanofibers aligned along the length of the tubes, allowing for customization of the length, diameter and thickness of the grafts. Combine that innovation with a way to make the nanofibers bioactive by attaching chemicals directly to the surface, and you've got a technology that mimics the nerve autograft by providing both physical and biochemical cues to direct nerve growth.
Armed with a potential breakthrough technology, things are moving quickly for NanoNerve. After graduating from Berkeley, Patel and a handful of others licensed the technology from the university and formed the company around it. They're currently in the development phase of the product, but according to Patel they're "actually very far along in the process. We hope to file for FDA 510k clearance by the end of the year, which will allow us to start marketing the product in 2009."
Assuming all goes well in human clinical trials, Patel sees NanoNerve taking off. "We'll be able to sell the product as something that is functionally better than what's currently available, something that will serve as an effective alternative to the autograft. Our technology takes full advantage of the fact that the shortest distance between damaged nerve endings is a straight line. It directs straightforward nerve growth and never lets them stray from the fast lane."
NanoNerve may very well be in the fast lane itself. And according to Patel, participating in the BMEidea competition has helped put it there. "The press and publicity as a result of winning third in BMEidea was very helpful in terms of getting the word out about what we're doing," he said. "It's helped the company since it shows that the project has scientific merit, shows that is has value to the medical community. It's helped us impress the people we've been talking to about it and has definitely validated what we're trying to do."
Massachusetts Institute of Technology, 2007 - $20,000
This E-Team is developing an inexpensive solar generator for powering off-grid communities in the developing world. Unlike standard photovoltaic panels, which only produce electricity, the team's device meets the entire range of commercial and residential energy needs: heating, cooling, and electricity. Using common, inexpensive auto parts and plumbing supplies, the generator works by using sun-tracking parabolic mirrors to focus the sun's rays on a pipe containing liquid anti-freeze. The refrigerant is heated and vaporized through a heat exchanger, driving a turbine-alternator assembly to generate electricity. Wasted heat is captured by a condenser and used to heat water. Altogether, the system costs about $3,000 and produces enough energy to power an off-grid school, health clinic or community center in the developing world.
The team is continuing to pursue the scaling and commercialization of this technology. There are two seprate ongoing efforts: a for-profit venture named Promethean Power (focus in India), and a non-profit named STG International (focus in Southern Africa).
Almost one billion people worldwide do not have access to safe drinking water, most of them in the developing world. To combat the problem, this E-Team is developing a water purification process in which contaminated water is put into a recycled plastic bottle coated with titanium dioxide and placed in the sun for several hours. This kills not only bacteria but other harmful substances such as arsenic and herbicides.
The team received a 2006 NCIIA grant to test this method and to develop a dye that turns clear when the water is fully disinfected and ready to use. They are now looking to bring the product to market by setting up microenterprises in villages in the Peruvian Andes and by partnering with a large bottled water company for manufacturing the bottles for sale.
Laparoscopic surgery, also called minimally invasive surgery, is a surgical technique in which operations in the abdomen are performed through small incisions (usually 0.5-1.5 cm), as compared to the larger incisions common in traditional surgical procedures. The key element in laparoscopic surgery is the use of a telescopic rod/lens system, usually connected to a video camera, called a laparoscope. Using carbon dioxide, the abdomen is blown up like a balloon, elevating the abdominal wall above the internal organs and giving the surgeon room to operate. This approach has a number of advantages, including reduced blood loss, which means less likelihood of needing a blood transfusion; a smaller incision, which means shorter recovery time; and less pain, which equals less pain medication needed.
The approach isn't without drawbacks, however, as one of the most frustrating and time-consuming parts of the surgery is closing the small port sites in the abdominal wall that are made when accessing the operative site. If the port sites are closed improperly, the patient is at increased risk of hernia or bowel problems, requiring further treatment. This E-Team has developed a solution to automatically, safely and reliably close the port sites. The 10mm device has two opposing wings that open when placed into a port. An indicator on the device alerts the surgeon when the wings are in their final position, and the surgeon locks the device into position by pushing a plunger that drives two flexible needles from the shaft into the wings. The surgeon then releases the wings and pulls out the device, leaving a looped suture around the port site opening.
Massachusetts Institute of Technology, 2007 - $19,930
Though many of the world's worst diseases can be treated with drugs, the problem of adherence--patients correctly following the timing and dosage of long, complex prescriptions--remains a major challenge in public health, especially in the developing world. To combat the problem, this E-Team has created uBox, a cheap, rugged, "smart" pillbox designed for rural communities in the developing world.
UBox is a palm-sized plastic container with sixteen compartments. The user rotates the top handle clockwise to expose a new compartment, and pulls down a small lid at the base of the device to retrieve medication. A simple electronic timer records each time the lid is lowered to remove pills, creating a log of when the patient takes the medication. Further, healthcare workers who are assigned to ensure patients take their pills are given a USB-like modified audio plug and insert it into a port on top of the uBox when visiting a patient. The uBox records the time and date of this action, allowing for healthcare worker tracking as well.
The team has formed Innovators In Health, Inc., a 501c3 working actively in eradicating TB. IIH runs two successful programs in India. In Delhi its biometric technology developed with Microsoft Research and Operation ASHA is now in a 600-700 patient trial. In Bihar, it works with India's national TB program and the Government of Bihar to improve access to TB for 50,000 rural residents in 19 villages.
Second product: Innovators In Health has started development of a biometrics platform called uPrint, which is now in a 700 patient trial in Delhi. The business model is that government agencies pay IIH for use of IIH technology.
Over seven million Americans suffer from Chronic Venous Insufficiency (CVI), a painful and debilitating disease that affects veins in the lower extremities. Veins in the legs have one-way valves that usually function to prevent blood from pooling at the feet, but malfunctioning valves can cause leg swelling, ulcerations, varicose veins, deep vein thrombosis, and pulmonary embolism, which can be fatal. Current treatments for CVI include anti-coagulant drugs, bed-rest and compressive legwear, but these target the symptoms of the disease rather than the cause. The standard surgical treatment is valve transplantation, but it's difficult to find suitable donor valves, and the surgery is highly invasive.
This E-Team has fabricated a prosthetic vein valve that can be implanted in a lower-risk, minimally invasive procedure. The valve is flexible, biocompatible, does not form blood clots, and can be manufactured cheaply. The team has shown that the valve is operationally functional; they are now performing pre-clinical tests in preparation for FDA approval.
According to the World Health Organization, 25% of the medicines sold in the developing world are inauthentic copies containing little or no active ingredients. When fake drugs are laced with lethal ingredients they can lead to mass fatalities, as was the case in a 1995 outbreak of false meningitis vaccine in Niger that killed 195,00 people. To fight the problem, this E-Team is developing an SMS protocol called UPAP. UPAP is a labeling system for drug manufacturers that allows customers to use their cell phones to text message covert, one-time alphanumeric codes to the drug company's back-end database for verification. The system verifies whether or not the drug is genuine, allowing the customer to get information on what they're buying right at the pharmacy.
A number of competing drug-verification technologies exist, such as RFID and colorimetric/holographic signatures, but none combine UPAP's low cost and high effectiveness. The team plans to focus initially on Ghana, where 40% of the drugs are counterfeit.
Update: a member of the original team has incorporated the venture as Sproxil, which has several partners, including the World Economic Forum Technology Pioneers Program, Ashoka, Nokia, and a number of telecoms carriers and pharmaceutical regulators in Ghana, Nigeria, and India.
This E-Team is developing the Extremely Low Frequency Seismic Detector (ELF-SD), a device designed to allow miners to communicate with rescuers on the surface in the event of a mine collapse. The device consists of an underground, battery-powered transmitter, a portable receiver, and custom software installed on a laptop. When a disaster occurs, ELF-SD transmitters located in predetermined safe rooms within the mines will send low frequency signals through the earth. By correlating the signals from these transmitters with specific safe rooms, rescue officials will get precise data on the location and condition of the workers, making rescue easier and possibly saving lives.
A number of miner tracking and mine communication products are on the market, but all depend in some way on an electronic network, which a mine collapse would obstruct and disable. The team believes their competitive advantage lies in the fact that their system would continue to function in the event of a collapse.
Update:Technology is licensed (July, 2011). The ELF team successfully negotiated a license with Strata Products Worldwide, LLC, to commercialize a low-frequency seismic detector that will enable miners trapped up to 2,000 feet underground to be located in a matter of hours. U.S. Mining companies have a legal mandate to retrofit all of their life refuge chambers starting in 2013, and as a result, the VMI device will soon make its way into almost every mine in the U.S.
Spinal fusion is a surgical procedure in which two or more vertebrae are fused together to relieve pain stemming from degenerative disc disease, spinal fractures, and other sources of back pain. The preferred surgical method is Transforaminal Lumbar Interbody Fusion (TLIF), where the disc is removed through an incision over the lumbar spine and a structural titanium cage and bone graft are inserted in its place. While this approach is less invasive than others and leads to lower trauma and complication rates, the small space in which to work and the vulnerability of local nerves make the surgery time-consuming and difficult to perform. Further, traditional cages have fixed dimensions and must be coaxed into the spine, possibly causing nerve damage.
This E-Team is developing a new approach to the procedure with an expandable fusion cage. The flexible titanium cage will be compressed during insertion and expanded during the positioning phase of the procedure. When the device is fit into the spine, a balloon will be inflated, expanding the cage to the exact size necessary and filling in all available space.
Urinary incontinence is a common, often embarrassing condition affecting millions of Americans. The most common form of the condition is Stress Urinary Incontinence (SUI), the involuntary leakage of urine when sneezing, coughing, or otherwise exerting yourself. While current surgical treatments are effective for most women with SUI, this E-Team believes there is a need for a reliable, minimally invasive treatment for patients with Intrinsic Sphinteric Deficiency (ISD), in which the urethra functions poorly despite normal anatomical support. Given the fact that all male cases of SUI are caused by ISD, the greatest unmet need lies in the male market.
The team has filed a provisional patent and developed an alpha prototype. With NCIIA funding the team will design and refine more prototypes, file for a full patent, and develop a business plan and marketing strategy.