News Article | November 4, 2014
Imagine a smartphone-sized device that creates a real-time 3D virtual window into your internal organs when you hold it up to your body — at a much higher resolution than conventional ultrasonography (which you see in the image above). This new tech would, I’m sure, make for quite a selfie. Armed with $100 million in seed money, and several patents for new ways to etch miniaturized ultrasonic devices directly into semiconductor wafers, tech entrepreneur Jonathan Rothberg is ready to do just that. But that’s not where it all ends. The same technology will enable precise delivery of ultrasonic power to destroy cancer cells, or communicate with devices inside the brain. Part of the funding for Rothberg’s startup company, called Butterfly Network, is being provided by Stanford University. Researchers there have recently taken the first experimental steps toward building practical ultrasound powered brain implants. The current state of the art uses a tiny piezo receiver to intercept ultrasonic energy. The total package of the Stanford device is pretty small, about the size of the tip of a ballpoint pen. What Rothberg is now proposing to build will blow these behemoths out of the water. The field of ultrasonics is currently undergoing a radical technological update. The writing on the wall is that the days of crude piezo devices are numbered. The details of Rothberg’s imaging device are probably not going to be released until the product is ready some 18 months from now, but a cursory look at the patents suggests they may be using something they call CMOS Ultrasonic Transducers or CUTs. CUTs appear to be similar to a related new technology which is taking the field by storm — namely the capacitive micromachined ultrasonic transducer or CMUT. Compared to stiff ceramic piezos, CMUTs can be made smaller and more sensitive. They also have better electromechanical coupling, can be batch produced to greater uniformity, and are better integrated with on-chip electronics into 2D or 3D arrays. As its name implies, a CMUT is basically an electrostatically-operated capacitor that has been micromachined into a silicon substrate. If an AC signal is applied to it, the vibrating membrane that sits over a vacuum will produce and transmit ultrasonic waves. Alternatively, if ultrasonic waves are applied to this membrane it will act as an ultrasonic receiver which generates an alternating signal as the capacitance of the CMUT is varied. The key advantage of this kind of design, aside from the features mentioned above, is that CMUTs have a greater frequency bandwidth. This directly translates into higher spatial and temporal resolution. While there are some challenges in this new technology, few would be better poised than Rothberg to use the power of semiconductor fabrication to attack biological problems. He recently sold Ion Torrent and 454 Life Sciences, his two DNA sequencing outfits, for over $500 million. The direct motivation for Rothberg’s founding of Butterfly Network is to help his daughter who now suffers from a disease called tuberous sclerosis. As we have recently seen for paralysis, there is no faster route to results than a high-tech billionaire personally incentivized to cure a disease. To image the damaging kidney cysts that form in tuberous sclerosis, or for that matter address the seizures which are a major complication, this technology is perhaps the best promise. For those that just have to know, the name name Butterfly Network comes from the field of linear network coding. It is basically a method of encoding signals in a network that can sometimes be more efficient than standard routing. Generally speaking, it involves combining two signals and sending the sum to an endpoint where they are then decoded. The company’s co-founder, Nevada Sanchez, previously used this particular technique to great effect in processing signals from radio telescopes. The technique may be handy in ultrasonics as well, but that is speculation. Given the power of this new ultrasonic technology, Butterfly Network may not be the only game in town. Handhelds from other places, like GE Healthcare’s Vscan Pocket Ultrasound, are already beginning to trickle out. But given the goals of making their device as affordable as a stethoscope, it hard to see that they will fail to capture the market.
News Article | November 2, 2014
Butterfly Network launches today with $100 million in funding to make a small handheld medical-imaging device that aims to make ultrasounds and MRIs faster, cheaper and smarter. Investors include Aeris Capital and Jonathan Rothberg, who previously sold his gene-sequencing startup Ion Torrent for more than $375 million. Butterfly is the first company to debut from Rothberg’s 4Combinator startup medical technology incubator. Butterfly’s device aims to “replace a room of imaging equipment that costs $2 million to $6 million dollars, and takes eight seconds to acquire an image,” Rothberg said. “We can do 30 to 60 times more per second, and be 10 times more precise in how we direct the energy.” It may sound a bit pie-in-the-sky for now, but this concept is parallel to what Rothberg has already done to make DNA sequencing cheap and accessible. Butterfly’s goal is to launch the device in as soon as 18 months — pending development and regulatory approval — with a price tag of hundreds of dollars, Rothberg said. How? By moving these machines onto a dedicated integrated circuit, and by hiring minds from different fields (for instance, an astronomer working on creating high-resolution images of the universe) to look at the problems with new eyes and lots of resources. Then there’s the next step: Analyzing lots and lots of images. Rothberg’s hope is that Butterfly can apply deep learning — the artificial intelligence technique used by companies like Google to hone features like speech recognition by modeling neural networks to handle massive amounts of data — to medicine. If all that goes well, it could mean smarter research and diagnoses without ever having to put a knife to a patient. And that is why Rothberg is approaching the broader tech community with his plans, he told Re/code. “Goldman Sachs and Google get all the resumes,” he said. “I want people to know they can come and build devices that could affect the life of someone you love.”
News Article | June 4, 2015
BOULDER, Colo.--(BUSINESS WIRE)--Today ArcherDX expanded its Archer™ FusionPlex™ assay menu to include the FusionPlex Lung Thyroid Panel and FusionPlex Solid Tumor Panel. The two panels are targeted next generation sequencing (NGS)-based assays that can be used to detect gene translocations in clinical samples types. The Lung Thyroid Panel simultaneously detects and characterizes fusions of 8 genes associated with NSCLC and thyroid cancer. The Solid Tumor Panel is the company’s largest catalog gene panel to date, detecting and identifying fusions and other mutations associated with over 50 different genes linked to carcinomas and solid tumors. The FusionPlex Solid Tumor Panel rounds out the company’s tumor fusion offering, complementing existing Heme and Sarcoma fusion panels to provide pan-cancer coverage of gene translocations. Both panels enable detection of fusions associated with the genes in the panel in a single sequencing assay, even without prior knowledge of fusion partners or breakpoints. “With the launch of these two assays, Archer has established itself as the clear leader in NGS-based fusion detection. With the FusionPlex Lung Thyroid Panel, we now offer robust fusion detection for the cancer with the highest mortality rate as well as the one with the highest growing incidence rate. And with the FusionPlex Solid Tumor Panel coupled with our complimentary Archer Analysis bioinformatics software, we now offer the most comprehensive fusion detection system,” says Jeff Mitchell, Product Manager at ArcherDX. The Archer FusionPlex Assays generate target-enriched cDNA libraries for NGS-based gene fusion detection. The system leverages Anchored Multiplex PCR (AMP™) to selectively amplify cDNAs of specific genes of interest in a sample along with any fusion partners, known or unknown. The FusionPlex system uses random start sites to improve sequence data quality and novel enrichment chemistry to yield a high on-target percentage FusionPlex assays are part of Archer’s targeted NGS mutation detection workflow that includes library preparation, analysis and reporting. Archer assays use a simple lyophilized workflow optimized to minimize hands-on time and risk of contamination in library preparation, making them ideal for high-volume laboratories. The AMP-enabled FusionPlex panels are target enrichment assays used to create libraries for Illumina® or Ion Torrent™ sequencing from small amounts (5-200 ng) of nucleic acid extracted from formalin-fixed, paraffin-embedded (FFPE) clinical samples. Once sequenced, the Archer Analysis software provides comprehensive analysis with embedded QC metrics and read visualization to accurately detect and identify known and novel fusions, SNPs, indels and CNVs. ArcherDX addresses the bottlenecks associated with using next-generation sequencing in translational research by offering a robust platform for targeted sequencing applications. Combining Anchored Multiplexed PCR (AMP) and easy-to-use, lyophilized reagents, our technology generates a highly enriched library of gene targets of interest for downstream genomic sequencing. Complemented by the Archer™ suite of bioinformatics software and readily accessible reports, AMP technology enables dramatic enhancement in mutation detection speed as well as complex mutation identification and discovery. ArcherDX offers FusionPlex panels to detect ALK, RET, ROS1, FGFR and NTRK fusions and those associated with sarcomas and hematological malignancies. ArcherDX is headquartered in Boulder, Colo., and maintains manufacturing operations in Beverly, Mass. Note: Archer kits and analysis software are for research use only and not for use in diagnostic procedures.
News Article | November 4, 2014
That massive MRI machine at the hospital that can look for damage inside your knee? It’s not just enormous. It’s enormously complex and expensive. And operating the thing takes not only time but expertise. The same goes for the ultrasound machine that a provides a look at your unborn baby. But entrepreneur Jonathan Rothberg says it doesn’t have to be this way. Rothberg just announced $100 million in funding for his three-year-old startup, Butterfly Network, that hopes to create a new handheld medical-imaging device that can make both MRI and ultrasounds significantly cheaper and more efficient. The aim is even to automate much of the medical imaging process, and in a little over a year, if all goes according to plan, the device could be ready for deployment in clinics, retail pharmacies, and in poorer regions of the world. It’s not an altogether unexpected endeavor from Rothberg, who has a wealth of experience in the biotech and semiconductor industry. He’s already launched five health startups, two of which—454 and Ion Torrent Systems—turned out to be successful DNA-sequencing companies that he sold for more than $500 million. The latter, Ion Torrent, crammed an entire expensive DNA sequencing machine into a single, cheap semiconductor chip. Similarly, with Butterfly, Rothberg says, he “took a step back and looked at bottlenecks in the healthcare system more broadly.” Butterfly’s handheld tool, Rothberg says, will walk users through the medical imaging process using on-screen instructions akin to Apple’s Panorama snapshot tool, and it will use ultrasound scanners to create 3D images in real-time. It will then send these to a cloud service, which will work to zoom in on certain identifying characteristics in the images and help automate diagnoses. As Rothberg explains it, the service could look at an ultrasound and notify doctors that a baby has Down syndrome or a cleft lip. This service will make use of “deep learning,” the same kind of artificial intelligence that’s starting to remake image and voice recognition inside web giants like Google, Facebook, and Microsoft. The more the imaging tool is used, according to Rothberg, the smarter it gets. The idea is to make using the device so easy that any technician or nurse practitioner can take advantage of it—without specific training in the device. Rothberg also aims to integrate telemedicine into the service, so that a specialist in a remote location can weigh in on the images that the instrument records. That way, he says, there’s potential to use the device in places in the world where there are fewer resources and a lack of people with technical knowledge, like radiologists. So far, Butterfly Networks has provided proof-of-concept that the ultrasound scanner can work, but the timeline to get an actual prototype built is 18 months. And the device represents only the beginning of Rothberg’s aspirations to disrupt healthcare. Butterfly Network is the first of the ventures to emerge from 4Combinator, a startup incubator launched by Rothberg with the goal to create and nurture companies that look for weak areas in the healthcare system and provide cheap and accessible solutions. Three other companies under 4Combinator have received between $5 million to $20 million in seed funding, and they’re exploring projects related to new treatments in tubular sclerosis and coming up with innovative ways to manufacture drugs. “This may be an inflection point with our understanding of human biology,” says Rothberg. “In the next ten years, we’ll see diagnostics as well as medicine change. And that will come from both medicine and devices, and the information systems that support them.”
News Article | June 3, 2011
Europe is currently suffering through what has now become the most deadly outbreak of E. coli bacteria on record. Although strains of this bacteria reside harmlessly in our guts (and in molecular biology labs around the world), others have picked up genes that enable them to resist antibiotics and cause hemorrhaging. That seems to be the case with the strain that's causing problems in Europe, as the first characterizations of the bacteria suggests they belong to a strain that was previously not on epidemiologists' radar screens. The spread of the infection, which is centered in Germany, is being tracked by the World Health Organization's European branch and Eurosurveillance . As of today, health authorities have identified 1,733 cases in Germany, 17 of which have been fatal. About 90 additional cases have been reported in 11 other countries, and one of those was fatal; that's enough to make this the most lethal E. coli outbreak yet. In part, this strain is killing via a route that's typical for E. coli, by causing hemorrhaging of the gut (enterohaemorrhagic E. coli). But it has also been triggering hemolytic-uremic syndrome, in which toxins from the bacteria in the gut escape into the blood stream and eliminate red blood cells, causing kidney damage in the process. The rates of kidney failure are apparently distinct to this strain. Right now, the source of the bacteria remains unknown; initial reports of "killer cucumbers" have turned out to be premature, as the strain found on those vegetables doesn't appear to be the same as the one causing severe problems. The strain itself has turned out to be a major surprise. Over the last several years, most outbreaks have involved the strain O157:H7 (the CDC is currently tracking a small outbreak of that strain in the US Midwest). In Germany, however, the cases are being caused by a strain called O104:H4, which has only been spotted rarely in humans—and not typically associated with any disease. What turned it into a killer? The general outlines are clear, but details are still very sketchy. It's clear that E. coli O104:H4 has picked up some new genes, almost certainly through horizontal gene transfer, in which stretches of DNA are picked up from other E. coli strains, or possibly different species entirely. Once incorporated into the genome, the new genes can provide the bacteria with entirely novel properties. In the case of E. coli O104:H4, tests have shown that it now carries a gene for shigatoxin, which is commonly found in other disease-causing strains of this species. German health officials have been cooperating with genomics centers to provide a clearer picture of what other genes might be causing its lethal effects, and a complete genome sequence has already been produced by BGI (the Beijing Genomics Institute). That sequence shows that the strain is most closely related to one seen previously in Africa, but that it has picked up several genes that cause intestinal hemorrhaging along with a number of antibiotic resistance genes. These results would suggest that only a limited amount of horizontal gene transfer was needed to make this strain deadly. Confusing matters, however, is Life Technologies, which is using the strain as an opportunity to show off its Ion Torrent DNA sequencing technology (which we've described previously). Life Tech is describing the new strain as a "hybrid," which implies more extensive exchange of DNA. Whether this is just a difference in terminology or represents a true difference between the results isn't clear. Since Life Technologies hasn't indicated that its data is public, the partial sequence it has can't be compared with the one from BGI to identify any differences. Currently, authorities are focused on limiting the further spread of this specific strain. The sudden transformation of E. coli O104:H4 into a deadly problem, however, points out how challenging it will be to prevent future outbreaks. The globalization of travel and overuse of antibiotics has ensured that bacteria will always have a rich source of new DNA to incorporate, which raises the risk of outbreaks popping up in unexpected places; the international agricultural trade also ensures that the actual disease outbreaks may occur in a different country entirely from the source. So it's essentially impossible to prevent future outbreaks, and even identifying the source will be extremely challenging. The O104:H4 experience also shows how challenging it will be to simply monitor the food supply for problems. Searching for the presence of something like shigatoxin might have identified the new bacteria as a risk, but wouldn't have identified the antibiotic resistance genes and additional toxins that have helped make it lethal. In a similar vein, researchers have recently identified a new strain of methicillin-resistant Staphylococcus aureus (MRSA). It has the gene used in the diagnostic test for MRSA, but the gene is so evolutionarily distant that the bacteria would not be identified using standard screening tests. Ironically, if we successfully combat MRSA using the standard test, we'll simply create a selective pressure that favors this atypical strain, which is already present in humans and the food supply. Evolution is a harsh mistress that way.