Synthetic biomarkers, bioengineered sensors that generate molecular reporters in diseased microenvironments, represent an emerging paradigm in precision diagnostics. Despite the utility of DNA barcodes as a multiplexing tool, their susceptibility to nucleases in vivo has limited their utility. Here we exploit chemically stabilized nucleic acids to multiplex synthetic biomarkers and produce diagnostic signals in biofluids that can be ‘read out’ via CRISPR nucleases. The strategy relies on microenvironmental endopeptidase to trigger the release of nucleic acid barcodes and polymerase-amplification-free, CRISPR-Cas-mediated barcode detection in unprocessed urine. Our data suggest that DNA-encoded nanosensors can non-invasively detect and differentiate disease states in transplanted and autochthonous murine cancer models. We also demonstrate that CRISPR-Cas amplification can be harnessed to convert the readout to a point-of-care paper diagnostic tool. Finally, we employ a microfluidic platform for densely multiplexed, CRISPR-mediated DNA barcode readout that can potentially evaluate complex human diseases rapidly and guide therapeutic decisions… Continue reading.
By tracing the steps of liver regrowth, MIT engineers hope to harness the liver’s regenerative abilities to help treat chronic disease.
The human liver has amazing regeneration capabilities: Even if up to 70 percent of it is removed, the remaining tissue can regrow a full-sized liver within months.
Taking advantage of this regenerative capability could give doctors many more options for treating chronic liver disease. MIT engineers have now taken a step toward that goal, by creating a new liver tissue model that allows them to trace the steps involved in liver regeneration more precisely than has been possible before.
The new model can yield information that couldn’t be gleaned from studies of mice or other animals, whose biology is not identical to that of humans, says Sangeeta Bhatia, the leader of the research team… Continue reading.
Using this diagnostic, doctors could avoid prescribing antibiotics in cases where they won’t be effective.
Many different types of bacteria and viruses can cause pneumonia, but there is no easy way to determine which microbe is causing a particular patient’s illness. This uncertainty makes it harder for doctors to choose effective treatments because the antibiotics commonly used to treat bacterial pneumonia won’t help patients with viral pneumonia. In addition, limiting the use of antibiotics is an important step toward curbing antibiotic resistance.
MIT researchers have now designed a sensor that can distinguish between viral and bacterial pneumonia infections, which they hope will help doctors to choose the appropriate treatment… Continue reading.
Most of the tests that doctors use to diagnose cancer — such as mammography, colonoscopy, and CT scans — are based on imaging. More recently, researchers have also developed molecular diagnostics that can detect specific cancer-associated molecules that circulate in bodily fluids like blood or urine.
MIT engineers have now created a new diagnostic nanoparticle that combines both of these features: It can reveal the presence of cancerous proteins through a urine test, and it functions as an imaging agent, pinpointing the tumor location. In principle, this diagnostic could be used to detect cancer anywhere in the body, including tumors that have metastasized from their original locations… Continue reading.
Harvard and MIT researchers teamed up to develop a novel screening test that could identify lung cancer a lot earlier and easier than current methods. The test detects lung cancer using nanoprobes, which send out reporter molecules that are picked up on urine analysis. This breakthrough, which is more sensitive than CT and delivers on a proof-of-concept experiment originally proposed in 2017, was recently detailed in a study published in Science Translational Medicine.
“What if you had a detector that was so small that it could circulate in your body, find the tumor all by itself, and send a signal to the outside world?” asked lead author Sangeeta Bhatia, MD, PhD, at a 2016 TED Talk. “It sounds a little like science fiction. But actually, nanotechnology allows us to do just that… Continue reading.
Study shows that a simple urine test can reveal the presence of lung cancer in mice.
People who are at high risk of developing lung cancer, such as heavy smokers, are routinely screened with computed tomography (CT), which can detect tumors in the lungs. However, this test has an extremely high rate of false positives, as it also picks up benign nodules in the lungs.
Researchers at MIT have now developed a new approach to early diagnosis of lung cancer: a urine test that can detect the presence of proteins linked to the disease. This kind of noninvasive test could reduce the number of false positives and help detect more tumors in the early stages of the disease.
Early detection is very important for lung cancer, as the five-year survival rates are at least six times higher in patients whose tumors are detected before they spread to distant locations in the body… Continue reading.
Sangeeta Bhatia, an MIT professor of electrical engineering and computer science and of health sciences and technology, and Richard Young, an MIT professor of biology, are among the 100 new members elected to the National Academy of Medicine today.
Bhatia is already a member of the National Academies of Science and of Engineering, making her just the 25th person to be elected to all three national academies. Earlier this year, Paula Hammond, head of MIT’s Department of Chemical Engineering, also joined that exclusive group; MIT faculty members Emery Brown, Arup Chakraborty, James Collins, and Robert Langer have also achieved that distinction… Continue reading.
Novel therapies based on a process known as RNA interference (RNAi) hold great promise for treating a variety of diseases by blocking specific genes in a patient’s cells. Many of the earliest RNAi treatments have focused on diseases of the liver, because RNA-carrying particles tend to accumulate in that organ.
MIT researchers have now shown that an engineered model of human liver tissue can be used to investigate the effects of RNAi, helping to speed up the development of such treatments. In a paper appearing in the journal Cell Metabolism on March 5, the researchers showed with the model that they could use RNAi to turn off a gene that causes a rare hereditary disorder. And using RNA molecules that target a different gene expressed by human liver cells, they were able to reduce malaria infections in the model’s cells.
“We showed that you could look at how this new class of nucleic acid therapies, especially RNAi, could affect rare genetic diseases and infectious diseases,” says Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science, a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science, and the senior author of the study… Continue reading.
Pneumonia, a respiratory disease that kills about 50,000 people in the United States every year, can be caused by many different microbes, including bacteria and viruses. Rapid detection of pneumonia is critical for effective treatment, especially in hospital-acquired cases which are often more severe. However, current diagnostic approaches often take several days to return definitive results, making it harder for doctors to prescribe the right treatment.
MIT researchers have now developed a nanoparticle-based technology that could be used to improve the speed of diagnosis. This type of sensor could also be used to monitor whether antibiotic therapy has successfully treated the infection, says Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science and the senior author of the study.
“If the patient’s symptoms go away, then you assume the drug is working. But if the patient’s symptoms don’t go away, then you would want to see if the bacteria is still growing. We were trying to address that issue,” says Bhatia, who is also a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science… Continue reading.
Glympse Bio has developed sensor technology that it says can give clinicians an early look at a developing disease. As Glympse prepares to test its disease detection approach in a serious liver disorder, the startup has raised $22 million in Series A financing.
LS Polaris Innovation Fund and Arch Venture Partners co-led the investment in Cambridge, MA-based Glympse.
The startup has developed bioengineered nanoparticles that circulate through the body, detect disease, and report their findings through a signal read by testing the patient’s urine. The company, which spun out from the laboratory of MIT professor Sangeeta Bhatia, says its “activity sensors” can test for multiple indicators of disease, such as cancer, fibrosis, immune disorders, and infectious disease. Glympse also says its technology can monitor how a patient’s disease is responding to a drug… Continue reading.
In her TEDMED talk, Harvard-MIT physician, bioengineer and entrepreneur Sangeeta Bhatia showed how miniaturization, through the convergence of engineering and medicine, is transforming health– specifically, through the promise of nanotechnology for early detection of cancer. She’s also been a huge advocate for the participation of women and girls in the Science, Technology, Engineering and Mathematics (STEM) fields. We asked her to share more about her dedication to empowering girls to develop their skills in the STEM fields.
What we desperately need: the best minds, and their talent.
In addition to your work in bioengineering, medical research and being a professor, you’ve been a huge advocate for the participation of women and girls in STEM-related fields. How are these two strands of your work related?
They are absolutely related! We need the best and brightest minds to realize these kinds of technological visions. The engineering pipeline is only 20-25% female; only 3% of tech startups are led by women. If I look around at the workforce in engineering at the moment in our country, it’s only 11 to 12 percent women. And the data shows that we lose women from this discipline all the way along what we call the ‘leaky pipeline’ that starts at age 11 and progresses all the way through to the workforce and to the board room– presently 40 percent of women who earn engineering degrees quit the profession or never enter the field at all.
Increasingly, innovation sparks from creative connections across disciplines. Drawing from deep expertise in several branches of science, some of our TEDMED speakers employ their own interdisciplinary knowledge to create breakthrough technology that is advancing healthcare and our understanding of human potential.
Also innovating at the nexus of technology and medicine is Sangeeta Bhatia, cancer researcher, MIT professor and biotech entrepreneur, who tells us, “I am #BreakingThrough academic silos to converge engineering and biology on medical innovations.”
Trained as both a physician and engineer, Sangeeta directs a laboratory that leverages “tiny technologies” of miniaturization to yield inventions with new applications in tissue regeneration, stem cell differentiation, medical diagnostics, predictive toxicology and drug delivery. She and her trainees have launched more than ten biotechnology companies to improve human health.
“As a young woman, the daughter of Indian immigrants, I didn’t have many role models for the path on which I found myself,” Sangeeta recalls. “Nonetheless, I had three mentors (all men) who saw more for me than I saw for myself in high school, college, and then graduate school. They believed in what I had to offer and invested time and energy in pushing me beyond my comfort zone. As a mentor now, I realize how important this is—to recognize talent, in all its forms, and to energetically support it.”
Sangeeta Bhatia MD, PhD, associate bioengineer at BWH, is one of six recipients of the 20th Heinz Award for Technology, Economy + Employment. The Heinz Award in this category honors individuals who have created and implemented innovative programs to advance regional or national economic growth through job creation, technology advancement, competitiveness and fair trade — all in a sustainable and environmentally safe manner. Recipients are selected by the Heinz Family Foundation for the $250,000 award.
Bhatia received the award for her success in growing artificial human microlivers, which has revolutionized screening for drug toxicity, and for her advocacy for the advancement of women in engineering.
Bhatia is the director of the Laboratory for Multiscale Regenerative Technologies at MIT. Her laboratory is dedicated to leveraging miniaturization tools from the world of semiconductor manufacturing to impact human health. Bhatia is also the founder of two companies that have put her discoveries, such as microlivers, into production. She is also a member of the Koch Institute for Integrative Cancer Research, the Ludwig Center for Molecular Oncology, the Harvard Stem Cell Institute and a senior member of the Broad Institute. Her work has been profiled in Scientific American, The Boston Globe, Popular Science, Forbes, PBS’s NOVA scienceNOW, The Economist and MSNBC.
A spoonful of yogurt could soon offer a cheap and simple way to screen for colorectal cancer.
Sangeeta Bhatia, a professor at MIT, is working to replace costly and uncomfortable colonoscopies and MRIs with a helping of yogurt followed by a urine test—a cheap method that could improve the early diagnosis of colorectal cancer.
Bhatia is developing synthetic molecules that can be introduced into the body via yogurt, and will interact with cancer in a way that produces telltale biomarkers. These molecules can then be detected easily when passed in urine.
Bhatia previously developed nanoparticles that find their way to tumors, and are then broken into smaller pieces by enzymes produced by the cancer. The broken up particles are small enough to be collected and concentrated by the kidneys, after which they are excreted.
The first iteration of the technique involved the use of lab instruments to analyze urine and find the telltale markers. Now Bhatia has developed a paper-based urine test—like the one you’d use for pregnancy. So far this test has been demonstrated in mice for colorectal cancer and liver fibrosis.
The nanoparticle work, described in a paper earlier this year, requires an injection (see “A Paper Diagnostic for Cancer”). In new, as-yet-unpublished work, Bhatia is developing a way to deliver the nanoparticles by modifying a type of bacteria found in yogurt. The bacteria produces the nanoparticle biomarkers by interacting with a tumor.
Bhatia hopes the approach will “transform diagnostics,” and says she’s in the process of forming a company to commercialize the approach. Because the test requires no specialized equipment, it will be particularly helpful in poor countries, she says, where few people are currently screened for common cancers. But it might also replace or augment colonoscopies.
Broad senior associate member Sangeeta Bhatia has been named the 2014 recipient of the $500,000 Lemelson-MIT Prize. The honor, which is celebrating its 20th year, recognizes outstanding, mid-career inventors who are improving the world through technological invention, and demonstrating a commitment to mentorship in science, technology, engineering, and mathematics.
Bhatia, a biomedical engineer and MIT professor, is being honored for her pioneering work in the design and commercialization of miniaturized technologies that aim to improve human health. That work includes the development of model human microlivers that can be used for studying human drug metabolism, drug-induced liver disease, and interactions with human pathogens. These microlivers have been used to study the liver stages of malaria, making it possible to screen drugs without testing them on patients. They may also be a basis for an engineered liver that could one day replace the need for human liver transplants.
Bhatia has also designed “synthetic biomarkers” for use in low-cost urine tests for cancer. This technology could eventually make it possible for physicians to detect cancer in places around the globe where they do not have access to more costly cancer screening tools. It’s also being leveraged for use in the detection of other diseases.