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Applied Biotechnology, Bioengineering, Global Health, Stanford News, Videos

Stanford microscope inventor featured on TED Talk

Stanford microscope inventor featured on TED Talk

Earlier today I wrote about the 50-cent paper microscope developed by Stanford bioengineering professor Manu Prakash, PhD. You can now watch a video of him building and demonstrating the microscope on TED.com. This TED “Talk of Week” has already been viewed almost 300,000 times.

Prakash, who grew up in the mega-cities of India without a refrigerator, is a leader in the frugal design movement. His lab is currently developing a number of global health solutions, leveraging the cost savings of emerging manufacturing techniques such as 3D printers, laser cutters and conductive ink printing.

Previously: Stanford bioengineer develops a 50-cent paper microscope, Stanford bioengineer developing an “Electric Band-Aid Worm Test and Stanford bioengineers create an ultra-low-cost oral cancer screening tool

Applied Biotechnology, Bioengineering, Global Health, Stanford News, Videos

Stanford bioengineer develops a 50-cent paper microscope

Stanford bioengineer develops a 50-cent paper microscope

Updated 6.18.14:Prakash demonstrated his invention at the first-ever White House Maker Faire this week. A paper further describing Foldscope was also published online in PLOS One.

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Updated 3.14.14: A second blog entry, including a link to Prakash’s TED talk on this topic, can be found here. And this entry discusses Prakash’s plans to give away 10,000 build-your-own paper microscope kits to citizen scientists with the most inspiring ideas for things to do with this new invention.

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3.11.14: When Manu Prakash, PhD, wants to impress lab visitors with the durability of his Origami-based paper microscope, he throws it off a three-story balcony, stomps on it with his foot and dunks it into a water-filled beaker. Miraculously, it still works.

Even more amazing is that this microscope — a bookmark-sized piece of layered cardstock with a micro-lens — only costs about 50 cents in materials to make.

In the video posted above, you can see his “Foldscope” being built in just a few minutes, then used to project giant images of plant tissue on the wall of a dark room.

Prakash’s dream is that this ultra-low-cost microscope will someday be distributed widely to detect dangerous blood-borne diseases like malaria, African sleeping sickness, schistosomiasis and Chagas.

“I wanted to make the best possible disease-detection instrument that we could almost distribute for free,” said Prakash. “What came out of this project is what we call use-and-throw microscopy.”

The Foldscope can be assembled in minutes, includes no mechanical moving parts, packs in a flat configuration, is extremely rugged and can be incinerated after use to safely dispose of infectious biological samples. With minor design modifications, it can be used for bright-field, multi-fluorescence or projection microscopy.

One of the unique design features of the microscope is the use of inexpensive spherical lenses rather than the precision-ground curved glass lenses used in traditional microscopes. These poppy-seed-sized lenses were originally mass produced in various sizes as an abrasive grit that was thrown into industrial tumblers to knock the rough edges off metal parts. In the simplest configuration of the Foldscope, one 17-cent lens is press-fit into a small hole in the center of the slide-mounting platform. Some of his more sophisticated versions use multiple lenses and filters.

To use a Foldscope, a sample is mounted on a microscope slide and wedged between the paper layers of the microscope. With a thumb and forefinger grasping each end of the layered paper strip, a user holds the micro-lens close enough to one eye that eyebrows touch the paper. Focusing and locating a target object are achieved by flexing and sliding the paper platform with the thumb and fingers.

microbes

Because of the unique optical physics of a spherical lens held close to the eye, samples can be magnified up to 2,000 times. (To the right are two disease-causing microbes, Giardia lamblia and Leishmania donovani, photographed through a Foldscope.)

The Foldscope can be customized for the detection of specific organisms by adding various combinations of colored LED lights powered by a watch battery, sample stains and fluorescent filters. It can also be configured to project images on the wall of a dark room.

In addition, Prakash is passionate about mass-producing the Foldscope for educational purposes, to inspire children — our future scientists — to explore and learn from the microscopic world.

In a recent Stanford bioengineering course, Prakash used the Foldscope to teach students about the physics of microscopy. He had the entire class build their own Foldscope. Then teams wrote reports on microscopic observations or designed Foldscope accessories, such a smartphone camera attachment.

For more on Foldscope optics, a materials list and construction details, read Prakash’s technical paper.

Previously: Stanford bioengineer developing an “Electric Band-Aid Worm TestStanford bioengineers create an ultra-low-cost oral cancer screening tool,
Related: Prakash wins Gates grant for paper microscope development

Applied Biotechnology, Bioengineering, Cardiovascular Medicine, Stanford News, Technology

Heart devices get a mobile makeover

Heart devices get a mobile makeover

AUM-close-up-chest560

Emerging diagnostic heart devices are going mobile. And by leveraging advances in smartphones and sensors, they’re able to perform their functions better, faster and cheaper than traditional heart monitoring equipment.

For example, the CADence, shown above, detects blocked arteries from the surface of the chest by identifying the noisy signals of blood turbulence associated with blockages.

The Zio Patch, on the right, is a sensor that can be worn on the chest for up to 14 days to detect intermittent, irregular heartbeats, called arrhythmias. ZIO-150-90

Both of these amazing devices reveal the mysteries of the heart non invasively, and they provide more potentially life-saving heart data to physicians than conventional equipment.

Yet despite these advantages, adoption into the medical system has been slow.

In the new issue of Stanford Medicine magazine on cardiovascular health, I interview the entrepreneurs behind these inventions — the heart gadgeteers — and let them describe the hurdles that add years to the process of launching new medical devices into the marketplace.

Previously: Mysteries of the heart: Stanford Medicine magazine answers cardiovascular questions, New Johnson & Johnson CEO discusses medical device futures at Stanford eventStanford physician-entrepreneur discusses need to change FDA approval process and Is the United States losing ground as a leader of medical innovation?
Photos courtesy of AUM Cardiovascular, iRhythm Technologies

Applied Biotechnology, Ethics, Events, Genetics, Stanford News

Coming soon: A genome test that costs less than a new pair of shoes

Coming soon: A genome test that costs less than a new pair of shoes

Air JordansScarcely a week ago, a leading genomics company, Illumina, announced it could sequence a human genome for the new, low price of $1,000. This week attendees at a personalized medicine conference heard a Silicon Valley startup say it would get the price down to $100.

Either price is a steep drop from the $2 million it cost in 2007 to sequence the genome of DNA discoverer James Watson, PhD. Illumina, a San Diego-based company (and one of Stanford’s partner  in a just-funded stem cell genomics center), claimed the $1,000 price in a Jan. 14 announcement on its latest sequencer model. CEO Jay Flatley said the achievement shows that science has “broken the sound barrier” in the race to make genome sequencing affordable for medical care.

Speaking Monday at the sixth annual Personalized Medicine World Conference in Mountain View, Calif., Flatley predicted that genome sequencing would one day become so widely used in bedside medical care that it would be regarded as a “molecular stethoscope.”

Skeptics at the conference questioned whether a $1,000 genome test could include all the interpretation and analysis necessary to make the raw data useful for patients. But within minutes of the question, another company stepped up to say it was already working on a test that would lower the cost even more to $100.

“At $100, you get to be really competitive,” said Stefan Roever, CEO of Genia Technologies, a startup based in Mountain View, during a panel presentation at the conference. Genia is using a different method, called nanopore-based sequencing. The start-up was part of a consortium with Harvard Medical School and Columbia University that won a $5.25 million grant in September from the National Human Genome Research Institute to develop the technology.

The PMWC conference was a mix of academic researchers, companies commercializing the genomics, and venture capitalists checking out the new crop of start-ups. Stanford was represented by Stephen Quake, PhD, professor of bioengineering; George Sledge, MD, professor of medicine; and a multitude of others. Also making presentations were LeRoy Hood, MD, PhD, head of the Institute for Systems Biology in Seattle, and Eric Green, MD, PhD, director of the National Human Genome Research Institute.

Amir Dan Rubin, president and CEO of Stanford Hospital & Clinics, gave a keynote talk at the start of the conference. Stanford Hospital & Clinics was one of the cosponsors of the conference, held Jan. 27-28 at the Computer History Museum in Mountain View.

Donna Alvarado is a Bay Area-based writer and editor who volunteers at the Stanford Health Library and finds inspiration in medical and health topics.

Previously: Stanford researchers work to translate genetic discoveries into widespread personalized medicineWhole-genome fetal sequencing recognized as one of the year’s “10 Breakthrough Technologies”New recommendations for genetic disclosure released and Ask Stanford Med: Genetics chair answers your questions on genomics and personalized medicine
Photo by rondostar

Applied Biotechnology, Genetics, Research, Science, Stanford News

RNA Rosetta stone? Molecules’ second, structural language predicted from their first, linear one

RNA Rosetta stone? Molecules' second, structural language predicted from their first, linear one

Rosetta stoneThe RNA whisperer is at it again.

In a study just published in Nature, Stanford’s Howard Chang, MD, PhD – an expert in all things RNA – and his colleagues detail how they were able to translate from one language spoken by this versatile biomolecule to another, more obscure but important one.

RNA is best known as the intermediate material in classic protein production. A so-called “messenger RNA” molecule serves as a mobile, short-lived copy of its more durable lookalike, DNA, the stuff genes are made of. Gene-reading machines in a cell’s nucleus produce RNA copies of protein-coding genes. Unlike a gene, which is a sequence of chemical letters situated somewhere on a big, bulky chromosome, a messenger RNA molecule can float out of the nucleus to the cell’s watery cytoplasm where proteins get made, and transmit a gene’s instructions to the protein-making machinery.

But RNA does more than simply specify which proteins are going to get made. A messenger RNA molecule’s 3-dimensional shape, for example, conveys bountiful information telling the cell’s protein-producing proletariat where to bring it, what to do with it when it gets there, and when and and how much protein to make from it.

DNA is famously double-stranded. That’s because, of its four component chemical “letters,” two in particular share a strong mutual attraction, biophysically speaking. Happily, the other two letters have a chemical crush on one another as well. So, when the letters composing one DNA strand are complementary to those on a closely opposed strand (and they virtually always are), the two strands lock in a lasting embrace to form a stable double helix.

RNA molecules are strings of four different chemical letters almost identical to those constituting DNA. But unlike DNA, an RNA molecule typically travels solo, as a single-stranded chain of those four chemical letters. It is thus a rather playful, floppy molecule. Nonetheless, the same alphabetical affinities that produce DNA’s double helix are at work in an RNA molecule, albeit in a more fleeting form: Small sequences of chemical letters along an RNA molecule find themselves attracted to complementary sequences elsewhere on the same molecule, causing it to fold into so-called secondary structures featuring pinched double-stranded sections alternating with bulges and loops, hairpins and hinges.

Chang’s gang has figured out how to predict, based on an RNA molecule’s linear chemical sequence, the way it will fold up into its secondary structure. They were able to do this for  thousands of differently shaped RNA molecules found in one type of human cell – about a thousandfold increase over the number of such structures that had been laboriously determined to date, Chang told me. That has consequences for understanding disease mechanisms and, potentially, for drug discovery as well.

Looks like RNA research is shaping up.

Previously: Night of the living dead gene: Pseudogene wakes up, puts chill on inflammation, New job description for RNA, oldest professional biomolecule and iPhone app shows 2D structures of thousands of RNA molecules
Photo by OliBac

Aging, Applied Biotechnology, Technology

Treating common forms of blindness using tissue generated with ink-jet printing technology

Treating common forms of blindness using tissue generated with ink-jet printing technology

eyes_011414The possibility of printing organs or tissues to treat a range of medical conditions is one that continually fascinates me. So I was interested to read about a new approach using a standard ink-jet printer to build tissue for repairing retinal damage.

Technology Review reports on why printing eye cells could be more effective than the conventional method of generating cells:

Scientists can grow single layers of cells in cultures, but printing may be a more effective way to engineer new tissues and organs, which are made of multiple different cell types positioned in intricate three-dimensional orientations. The retina, for example, is a highly organized, multilayered structure composed of various types of neurons and non-neuronal cells. The new ink-jet technique makes it possible to place retinal cells in “very precise and special arrangements,” says [University of Cambridge professor Keith Martin, who led the research].

Rebuilding the retina is an extremely difficult challenge, because “you have to reconstruct what is basically a small computer” whose function arises from a very complicated architecture in which multiple cell layers are connected in a number of different ways, says Joel Schuman, chairman of the department of ophthalmology at the University of Pittsburgh. If this architecture could be re-created using a printer, “you would be so many steps ahead of trying to grow the layers individually and then put them together,” he says.

The piece goes on to explain how printed eye cells could be used in treating common forms of blindness including macular degeneration, which is the leading cause of blindness.

Previously: Stanford researchers develop solar-powered, wireless retinal implantAustralian scientists implant early prototype of a “bionic eye” into a patient, Stanford-developed retinal prosthesis uses near-infrared light to transmit images and Developing a prosthetic eye to treat blindness
Photo by Scinern

Applied Biotechnology, Microbiology, Patient Care, Research, Stanford News, Surgery

Staphylococcus aureus holes up in upper nasal cavity, study shows

Staphylococcus aureus holes up in upper nasal cavity, study shows

nostrilsA posse led by Stanford microbe sleuth and microbiologist David Relman, MD, has apprehended Staphylococcus aureus, one of the most notorious sources of serious infections, lurking in formerly unsuspected nasal hideaways. The discovery may explain why attempts to expunge S. aureus from the bodies of hospitalized patients being readied for surgery often meet with less than perfect results.

About one in three of us are persistent S. aureus carriers, and another third of us are occasional carriers. This bacterial shadow, which abounds on skin (especially the groin and armpits) and is quite at home in the nose, does us no harm most of the time. But if it gets into the bloodstream or internal organs, it can cause life-threatening problems such as sepsis, pneumonia and endocarditis (infection of heart valves). That makes S. aureus not such a good thing to be coated with if you’re about to have your skin punctured by a catheter or pierced by a scalpel.

This is exacerbated by the all-too-frequent presence, particularly in hospital settings, of S. aureus strains resistant to an entire family of antibiotics related to methicillin. In 2011, more than 80,000 severe methicillin-resistant S. aureus infections and more than 11,000 related deaths occurred in the U.S. alone, along with a much higher number of less-severe such infections.

In a study just published in Cell Host & Microbe, Relman – who pioneered the use of ultra-high-volume gene-sequencing techniques to sort out the thousands of species of microbes that communally inhabit our skin, orifices and innards – and his team used this method to show that mucosal sites way up high in our nose, where standard S. aureus-elimination techniques may not reach, can serve as reservoirs for S. aureus. That may, at least in part, explain why efforts to rid patients of this potentially nasty bug have so often fallen short of the mark, as I noted in my news release about the new findings:

Rigorous and somewhat tedious regimens for eliminating S. aureus residing on people’s skin or in their noses do exist, but it’s typically a matter of weeks or months before the bacteria repopulate those who are susceptible. The new study offers a possible reason why this is the case.

Previously: Cultivating the human microbiome, Anti-plaque bacteria: Coming soon to your toothpaste? and Eat a germ, fight an allergy
Photo by OakleyOriginals

Applied Biotechnology, Ethics, Fertility, Genetics, Medicine and Society, Parenting

Medical practice, patents, and “custom children”: A look at the future of reproductive medicine

Medical practice, patents, and "custom children": A look at the future of reproductive medicine

black and white baby

Recently, 23andMe, the direct-to-consumer genetic diagnostic company, announced it had been issued a patent for a system of applying genetic testing – and, consequently, genetic screening – to egg and sperm banks. (Full disclosure: I am a 23andMe consumer.) In brief, 23andMe’s system involves receiving information from would-be parents about which traits they’d like their children to possess, and then determining which egg or sperm donations would be the best genetic fit to create those children. While egg and sperm banks currently allow would-be parents to sort through the traits of egg and sperm donors – such as race, height, athleticism, and even SAT scores – 23andMe’s patent envisions applying statistics to the genetic profiles of both donors and recipients to create something of a “custom child.”

To be clear, 23andMe’s patent is just that: a patent. There’s no indication that 23andMe has put its system into implementation or even made a serious business attempt to do so. Nonetheless, others have discussed the ethics behind 23andMe’s system, the propriety of the patent, and 23andMe’s ultimate plans with its intellectual property. But one question I’m particularly intrigued by is: Assuming 23andMe’s vision comes to pass – one easily within our technological if not cultural grasp – what will the future of reproductive medicine look like?

First, it would be a tremendous boon to the medical care of those “custom children,” as it would likely eliminate many common gene variants responsible for disease. These range from simple, single-gene diseases, such as Marfan syndrome, spinal muscular atrophy, and Huntington’s disease, to complex multi-gene diseases, such as breast and ovarian cancer, for which certain gene variants play a significantly large etiological role. And, as is demonstrated by the list above, these diseases need not be limited to the traditional fatal-in-childhood diseases, such as Tay-Sachs or Niemann-Pick syndrome, that are currently screened for. Rather, as is the case with Huntington’s disease, which only afflicts its sufferers in mid-life, the method could quash those genetic variants that cause disease through all stages of life.

Second, the robustness of the technology behind the 23andMe patent may spur demand for  in vitro fertilization. Few couples capable of conceiving without technological intervention undergo IVF today. But some of that is ultimately a matter of choice: that there are few benefits to be had through IVF relative to natural conception. The possibilities for customization described in the 23andMe patent – choosing a child possessing hundreds of hand-picked traits, from curly hair down to caffeine metabolism – may, at least for some, change that calculus. The potential for customization drives demand in other enterprises – smartphones, cheeseburgers, insurance policies, even house paint. It’s culturally naïve to think it will have no effect on reproductive technology.

And lastly, I suppose it also means that reproductive medicine will increasingly come within the ambit of patent law. Since its inception in the 1970s, IVF has largely been free of the destructive and costly patent litigation seen in other industries, such as smartphones. If 23andMe’s patent is indicative of a future norm, reproductive medicine may very well operate in a world controlled by licensing agreements and cowered by threats of litigation. Whether one is entitled to a particular genetic screening method may have little to do with the quality of the institution – as it generally does now – but more with whether an institution has agreed to pay the appropriate royalties. At least this aspect of reproductive medicine is not so futuristic: The current set of patent infringement lawsuits among Verinata, Sequenom, Natera, and Ariosa has held up much non-invasive, prenatal screening for Down’s syndrome.

These issues are both fascinating and complex, and the larger concerns raised by the system described in the 23andMe patent only touch a small fraction of the ethical and practical quandaries involved. For a discussion of the remainder, Stanford’s own Hank Greely, JD, will attempt to address them in his upcoming book, “The End of Sex“. Let us at least hope that that institution’s end is not because of patents.

Jake Sherkow, JD, is a fellow at Stanford Law School’s Center for Law and the Biosciences. His current research focuses on the intersection of patent law, biotechnology, and agency regulation.

Previously: Whole-genome fetal sequencing recognized as one of the year’s “10 Breakthrough Technologies”Stanford bioethicists discuss pros, cons of biotech patents, The end of sex? Maybe not just yet, New techniques to diagnose disease in a fetus, and Sex without babies, and vice versa: Stanford panel explores issues surrounding reproductive technologies
Photo by Lisa Williams

Applied Biotechnology, In the News, Science

The history of biotech in seven bite-sized chunks

Yesterday, an absolute gem appeared on Smithsonian.com’s blog Around the Mall: an assemblage of objects that neatly summarizes the progression and history of biotechnology. Before you stifle a yawn, remember these are the same people who made a paper bag exciting.

Through these seven photos of seven objects the Smithsonian masterfully tells the story of how the first synthetic insulin, Humalin, came to be and how technology used for genetic research advanced in the process. These objects, acquired from the San Francisco company Genentech, can be viewed at the American History Museum in an exhibit called “The Birth of Biotech.”

From the blog:

Genentech’s work began with a discovery made in the 1970s by a pair of Bay Area scientists, Herbert Boyer [PhD] of UC San Francisco and Stanley Cohen, MD, of Stanford: Genes from multi-cellular organisms, including humans, could be implanted into bacteria and still function normally. Soon afterward, they teamed with venture capitalist Robert Swanson to form the company, with the hope of using genetic engineering to create a commercially viable product.

One of their first achievements was synthetically building the human insulin gene in the lab, a single genetic base pair at a time. In order to check the accuracy of their sequence, they used a technique called gel electrophoresis, in which electricity forces the DNA through a gel. Because larger pieces of DNA migrate more slowly than smaller pieces, the process effectively filters the genetic material by size, allowing researchers to pick out the pieces they want, one of the key steps in early genetic sequencing methods.

Holly MacCormick is a writing intern in the medical school’s Office of Communication & Public Affairs. She is a graduate student in ecology and evolutionary biology at University of California-Santa Cruz. 

Previously: The dawn of DNA cloning: Reflections on the 40th anniversaryGenetic basis for anthrax susceptibility in humans discovered by Stanford scientists and Potential therapeutic target for Huntington’s disease discovered by researchers in Taiwan, Stanford

Applied Biotechnology, Bioengineering, Immunology, Research, Stanford News, Stem Cells

Alchemy: From liposuction fluid to new liver cells

Alchemy: From liposuction fluid to new liver cells

alchemyHow’s this for modern-day medical alchemy: A team led by Stanford’s Gary Peltz, MD, PhD, has found a fast, cheap, efficient way for regenerating liver tissue from a patient’s own fat cells. Let it be immediately said that the “patients” in this endeavor (described in a just-published study in Cell Transplantation) were mice. But the fat cells that Peltz’s team used as starter materials and the liver tissue that grew inside the mice (replacing their own organs, which had experienced severe poisoning not unlike that caused by a Tylenol overdose) were completely human.

The liver – the body’s chemistry set – builds complex biomolecules we need and filters and breaks down waste products and toxic substances we need to get rid of. Unlike most organs, a healthy liver can regenerate itself to a significant extent. But this ability is no match for acute liver poisoning or damage from chronic alcoholism or viral hepatitis. Acute liver failure from acetaminophen (Tylenol) alone takes a toll of about 500 lives every year and accounts for upwards of 60,000 emergency-room visits annually.

That begets an ongoing, life-threatening liver shortage. From my release on the study:

Some 6,300 liver transplants are performed annually in the United States, with another 16,000 patients on the waiting list. Every year, more than 1,400 people die before a suitable liver can be found for them. While it can save lives, liver transplantation is complicated, risky and, even when successful, fraught with aftereffects. Typically, the recipient is consigned to a lifetime of taking immunosuppressant drugs to prevent organ rejection.

Making new livers out of a patient’s own readily retrieved fat tissue could help plug the gap between the number of available donor livers for transplantation and the number of people in dire need of that procedure. It might also go a long way to alleviating the requirement for lifelong immunosuppressant therapy afterward.

Peltz’s team obtained adipose stem cells, which ordinarily grow up to be fat cells, from fat-filled fluid removed during routine liposuction procedures. The team then put these cells through a series of biochemical hoops that caused them to change their minds and decide to be liver cells instead.

That’s not easy. (“We had to work hard to convert them to liver cells,” Peltz told me.) But it’s been done before. The problem was that previous fat-to-liver methods took longer than a patient with acute liver failure can survive, and were inefficient and expensive to boot. Using a new technique, Peltz’s group was able to get enough good liver cells for the next regenerative step – injecting the cells into mice’s liver cavities – within seven or eight days. A month later the mice exhibited healthy human liver formation and activity. Importantly, inspection at two months out showed no signs of tumor formation, which is a big obstacle to the alternative use of human embryonic stem cells or induced pluripotent stem cells for this purpose.

Peltz hopes to see the new technology enter clinical trials within a couple of years.

Previously: Fortune teller: Mice with ‘humanized’ livers predict HCV drug candidate’s behavior in humans, Free database of drugs associated with liver injury available from NIH and Hepatitis C virus’s Achilles heel
Photo by Abode of Chaos

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