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Fly-snatching robot speeds biomedical research

Fly-snatching robot speeds biomedical research

The drosophila hangs unharmed lifted by the robot’s suction tube.

It looks like nothing so much as a miniature UFO hovering over a plate of unsuspecting flies. When it’s ready to strike, it flashes a brief infrared blast of light that reflects off the animals’ backs, indicating the location of each insect. Then, a tiny, narrow suction tube strikes an illuminated thorax, painlessly sucking onto the fly and carrying it away.

It’s not the greatest new gadget to rid your kitchen of unwelcome pests, it’s the latest biomedical research tool from applied physicist Mark Schnitzer, PhD.

The flies in question are commonly studied in biology labs as a proxy for our own harder-to-access cells and organs. As I wrote in a press release:

Although flies and humans have obvious differences, in many cases our cells and organs behave in similar ways and it is easier to study those processes in flies than in humans. The earliest information about how radiation causes gene mutations came from fruit flies, as did an understanding of our daily sleep/waking rhythms. And many of the molecules that are now famous for their roles in regulating how cells communicate were originally discovered by scientists hunched over microscope staring at the unmoving bodies of anesthetized flies.

Until now, scientists have had to anesthetize the flies and painstakingly assess them by microscope. The robot and its machine vision can assess physical features more quickly and in finer detail than lab personnel and can carry out behavioral studies of awake flies.

I spoke with Joan Savall, PhD, a visiting scientist from the Howard Hughes Medical Foundation, who led the development of the robot. He says it will speed research because the robot is both faster and less sleepy that your average graduate student, but what’s really cool is that it opens up entirely new areas of research.

“In the end you can really push many fields at the same time,” he told me.

Previously: Thoughts light up with new Stanford-designed tool for studying the brain and New tool for reading brain activity of mice could advance study of neurodegenerative diseases
Image by Linda Cicero

Bioengineering, Cardiovascular Medicine, Stanford News

From popsicle sticks to improved medical care

This post is part of the Biodesign’s Jugaad series following a group of Stanford Biodesign fellows from India. (Jugaad is a Hindi word that means an inexpensive, innovative solution.) The fellows will spend months immersed in the interdisciplinary environment of Stanford Bio-X, learning the Biodesign process of researching clinical needs and prototyping a medical device. The Biodesign program is now in its 14th year, and past fellows have successfully launched 36 companies focused on developing devices for unmet medical needs

IMG_6141 300Shashi Ranjan, PhD, and Harsh Sheth, MD, fiddled with popsicle sticks and tiny wires in the final throes of prototyping possible biodesign solutions for two medical needs: fixing pacemaker leads or improving catheter urine drainage.

The popsicle stick device hardly looked like something that would inspire confidence in a person undergoing surgery, but if it worked and could be miniaturized and made out of more durable materials it could provide a solution for the pacemaker leads that are prone to coming unfixed after they are inserted.

The team had narrowed their search down from the 315 medical needs they had originally identified using a weighted matrix of requirements. Sheth told me that what stood out about addressing the final two needs was the large number of people who could benefit, lack of other solutions and lack of competing products.

All of those add up to a product that could inspire venture funding and eventual development, which is the goal of the biodesign process.

Sheth said the prototypes they were building now would help determine which of the two needs the group eventually chose to address, and how. They had four ideas to try out for the pacemaker leads and five ideas for improving urine drainage. “We’ll know which of these ideas have value after this step,” Sheth told me.

The group (which includes Debayan Saha, who was elsewhere during this prototyping session) returns to India after the Stanford phase of the fellowship ends in June. At that point they’ll repeat the process of identifying medical needs and prototyping solutions in India. Sheth and Ranjan said they hope to have patents in place for their Stanford prototype, with the idea of potentially returning to it after the fellowship.

Previously: The next challenge for biodesign: constraining health-care costsFollowing the heart and the mind in biodesign and Stanford-India Biodesign co-founder: Our hope is to “inspire others and create a ripple effect” in India

Ask Stanford Med, Bioengineering, Cardiovascular Medicine, Stanford News, Technology

The next challenge for biodesign: constraining health-care costs

The next challenge for biodesign: constraining health-care costs

This post is part of the Biodesign’s Jugaad series following a group of Stanford Biodesign fellows from India. (Jugaad is a Hindi word that means an inexpensive, innovative solution.) The fellows will spend months immersed in the interdisciplinary environment of Stanford Bio-X, learning the Biodesign process of researching clinical needs and prototyping a medical device. The Biodesign program is now in its 14th year, and past fellows have successfully launched 36 companies focused on developing devices for unmet medical needs.

5445002411_0f22229afd_z 300Founder and director of the Stanford Biodesign Program Paul Yock, MD, describes himself as a “gismologist.” His inventions include a balloon angioplasty system that is in widespread use and many other devices primarily related to ultrasound imaging of the vascular system. I recently spoke with him about the program he helped found, the iterative biodesign process, and the ongoing relationship with the Stanford-India Biodesign Program.

What’s next for the Stanford Biodesign Program?

We’ve been really pleased with the results of the Biodesign Program so far in terms of being able to take newcomers into the process, then repeatedly and reliably seeing good ideas coming out and seeing patients getting treated from those good ideas.

The challenge is that the world has changed profoundly since we founded this program. There’s no question that new technologies – despite being good for patients – contribute to escalation of health-care costs. We are in a phase of reinventing our process to take into account the fact that the sickest patient in the system is the system itself. We have to invent technologies that help constrain costs. We will need to modify the process of needs-finding not only to look for important clinical needs but important value needs as well. Inventors in general don’t like thinking about economics and so we have to not only figure out how to update the process but also figure out how to make it attractive for our fellows to learn and practice.

Could the India fellows help you incorporate affordability into the process?

One of the big reasons we decided to do the India program in the first place was to shock our system into thinking about really affordable technology innovation. It is remarkable how good our fellows from India are at thinking this way and how immersed they have been from an early age with value-based design and invention.

Affordability is very much a part of the Indian culture and technology innovation is clearly something that we are very good at here. I think we have only started to capitalize on the fusion of their culture and ours. I think there is a hybridization here that really is going to be cool. Our grand strategy is to have a number of different platforms – it could be companies, incubators, or other experiences – where our fellows can get a deep exposure in India. We aren’t fans of parachuting people in for two weeks to invent something good to give to India. What we really want to do is have trainees get a deep experience in what it’s like to invent and develop technologies in that setting to influence the way we invent here.

How did you arrive at the drawn out, iterative process the fellows use to identify medical needs they want to address?

There’s a long tradition of what is called user centered design that says if you want to design a product you need to talk to the user and understand what their needs are. That’s essentially where our process starts. What’s fundamentally different with health care is that there isn’t just one user. There’s this really complex network of stakeholders who influence whether a technology will actually make it into patient care. You can’t just design for the patient because there are also the doctors, nurses, hospitals, insurance companies, regulatory agencies and financers to name a few. To make it all still more complex, this whole system is in tremendous flux because of health-care reform.

So what we’ve done is blow out the needs characterization stage to take all these stakeholders into account in a rigorous way, up front, before any inventing happens.  There’s also a bit of psychology at play here. In health care it is really easy to fall in love with the first need that comes your way. Looked at in isolation, pretty much any clinical need looks compelling. You need to put in a disciplined process, a semi-quantitative way of weighing one need against the other in order to make a good decision about which need to pursue. It is easier to get rid of the one you thought you loved if it really doesn’t meet the criteria you set out.

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Bioengineering, Cardiovascular Medicine, Stanford News, Technology

Defining a new way of thinking: Slower decisions could result in better medical devices

Defining a new way of thinking: Slower decisions could result in better medical devices

This post is part of the Biodesign’s Jugaad series following a group of Stanford Biodesign fellows from India. (Jugaad is a Hindi word that means an inexpensive, innovative solution.) The fellows will spend months immersed in the interdisciplinary environment of Stanford Bio-X, learning the Biodesign process of researching clinical needs and prototyping a medical device. The Biodesign program is now in its 14th year, and past fellows have successfully launched 36 companies focused on developing devices for unmet medical needs.

2331754875_e6a2a81429_zIt’s now early April – half way through the six-month fellowship – and the Stanford-India Biodesign fellows are still figuring out what medical need they’re going to address during their time at Stanford. On June 8 they’ll be revealing prototypes. For many past students in this program, those prototypes have gone on to launch successful companies.

That’s not to say that the fellows are slow, it’s just to say that the Biodesign process the fellows are learning takes time – more time than I, for one, had expected.

I asked the fellows if they thought they would be able to take this painstaking approach into the real world, where people make much faster and often less careful decisions when developing medical devices.

“We hope this will define a new way of thinking,” Debayan Saha, one of the fellows, told me. As a group they also said they were learning a lot about the value of slow decisions.

As an example, they pointed to one of the 35 medical needs still on the “maybe” list, down from more than 300 they had identified during clinical visits. This one had to do with measuring levels of molecules in the blood. At each step, they’d scored the medical needs on their list against a criterion, like the number of people it applied to or the cost of letting that need go untreated. That allowed them to strategically eliminate needs that seemed worth addressing at first blush, but that wouldn’t make business sense.

At each round, this one medical need scored near the top. It had been looking like a real contender for the one they might eventually chose to address.

Then came today, when the fellows were scoring whether other devices already address the need and the cost spent each year if the need wasn’t addressed. That gave them a sense of whether there was a market for any device they might develop. That need, which had seemed so strong, scored low, much to the team’s surprise.

“This had been a favorite but this is the first time we are seeing that it is maybe not a great need,” Shashi Ranjan, PhD, told me. Harsh Sheth, MD, emphasized that in other settings where people make much faster decisions they might have ended up wasting time prototyping a device that would never find a place in the market.

To my eye, this careful approach makes the final selection almost seem inevitable (though not obvious at the outset). The team knows the criteria they have to meet (good market size, few competing devices, no patents standing in the way of eventually marketing their device) and they have a list of options.

From there, it’s a matter of slowly assessing which option best fits the criteria, which seems like a lesson that goes well beyond designing medical devices: Choosing health insurance. Buying cars. They are learning a lesson in good decision-making along with how to develop and market devices.

Previously: Following the heart and the mind in biodesignWriting a “very specific sentence” is critical for good biodesign and Stanford-India Biodesign co-founder: Our hope is to “inspire others and create a ripple effect” in India
Photo by John Morgan

Bioengineering, Cardiovascular Medicine, Stanford News, Technology

Following the heart and the mind in biodesign

Following the heart and the mind in biodesign

This post is part of the Biodesign’s Jugaad series following a group of Stanford Biodesign fellows from India. (Jugaad is a Hindi word that means an inexpensive, innovative solution.) The fellows will spend months immersed in the interdisciplinary environment of Stanford Bio-X, learning the Biodesign process of researching clinical needs and prototyping a medical device. The Biodesign program is now in its 14th year, and past fellows have successfully launched 36 companies focused on developing devices for unmet medical needs.

15125593898_7ee05d0a60_zWhen I showed up to meet with the Biodesign fellows, Debayan Saha greeted me by saying, “We are arguing – please join us.”

The source of the argument turned out to be a thorny one. The team had previously attended cardiovascular disease clinics and from those visits identified more than 300 possible needs that, if addressed, might improve patient care.

Now, their job was to narrow down those 300+ needs to the one they would eventually develop a prototype device to address.

Part of the process Stanford Biodesign fellows learn is a rigorous method for identifying medical needs that also make business sense to address. The first step: eliminate the duds.

In this round, the each team member had individually rated the needs according to their individual levels of interest on a scale of 1 to 4. That interest could reflect the fact that they think the technology is interesting, or the fact that the need is one they would be excited about addressing.

Now they were trying to rate the needs on the same 1 to 4 scale according to the number of people who would benefit if it were addressed. The combination of these two ratings—one subjective and the other objective—would produce a shorter list of needs that were both of interest to the fellows and would benefit enough people that any future company could be successful

That objective rating was the source of the polite disagreement I had walked into. As one example, if a particular need applied to people who had a stroke, should they assume that all people who have had a stroke would benefit from a solution (giving the need a higher rating of 4), or would only a small subset benefit (giving the need a lower rating of 1 or 2)?

By and large Harsh Sheth, MD, leaned toward 4s while Shashi Ranjan, PhD, leaned toward 2s. Saha mostly just leaned back. Much discussion ensued.

In the end the team managed to assign a single score indicating the number of people represented by each need. When combined with their subjective scores, the group was able to eliminate the lowest scoring needs and reduce the list to a mere 133.

One interesting thing I learned is that this careful rubric is harder to apply in India, where good numbers about how many people have particular conditions are harder to come by. Ranjan told me that even in India they would likely use U.S. numbers for some conditions and just scale up to the Indian population. I mentally added this lack of good data to the list of reasons Stanford-India Biodesign Program executive director (U.S.) Rajiv Doshi, MD, told me that biodesign is more challenging in India.

Previously: Writing a “very specific sentence” is critical for good biodesign and Good medical technology starts with patients’ needs
Photo by Yasmeen

Ask Stanford Med, Global Health, Stanford News, Technology

Stanford-India Biodesign co-founder: Our hope is to “inspire others and create a ripple effect” in India

Stanford-India Biodesign co-founder: Our hope is to "inspire others and create a ripple effect" in India

This post is part of the Biodesign’s Jugaad series following a group of Stanford Biodesign fellows from India. (Jugaad is a Hindi word that means an inexpensive, innovative solution.) The fellows will spend months immersed in the interdisciplinary environment of Stanford Bio-X, learning the Biodesign process of researching clinical needs and prototyping a medical device. The Biodesign program is now in its 14th year, and past fellows have successfully launched 36 companies focused on developing devices for unmet medical needs.

shutterstock_258773231Rajiv Doshi, MD, is the executive director (U.S.) of the Stanford-India Biodesign Program and was part of the Stanford team that initially flew to India in 2007 to propose the program to the Government of India. He has commercialized devices to treat sleep apnea and snoring and later served on boards of multiple medical device companies. In 2012 he was named by Forbes India as one of the top 18 Indian scientists who are changing the world.

Doshi answered questions about the early days of the Stanford-India Biodesign program and the hurdles entrepreneurs face in India.

Why did you want to start the Stanford-India Biodesign program?

Starting the program was both an opportunity and an obligation. My belief was that this was going to be a difficult challenge spanning perhaps a decade. We were working with a partner [the Indian government] where we didn’t know the people very well and we didn’t know many of their systems. We had never assembled such an international collaboration of this scale. If we failed then at least we tried and did our best. If we were successful then we would have helped a lot of people. I felt that this was a once in a lifetime opportunity to have an impact of this scale.

What were some of the hurdles the early fellows faced when they tried to develop technologies in India?

Probably the number one problem they face in India is that there is really little mentorship as we know it here. Few people in India have successfully developed a medical device from scratch so it is really hard to find mentors who are already domain experts in medical technology. The next issue is raising capital. There is very little early stage venture capital focused on medical technology in India.

Then there are challenges with research and development. Imagine you’re creating a difficult-to-make medical device that has small, complicated parts. Odds are the suppliers aren’t available for all these parts in India. Then there’s manufacturing and supply chain issues. Let’s say the entrepreneurs are able to develop a product, then they may struggle to find an in-country manufacturer to make this product. In many cases, in-country manufacturing capabilities just aren’t at the same level as you would see here or in Singapore, Germany or other locations. So you start stacking these challenges together and you realize that they are pretty serious.

Does it get easier once they’ve developed the device?

No, I think the greatest challenges are related to commercialization – after development has been completed. Let’s imagine you created a great product, you’ve figured out all these issues. Your next challenge is then to market your product and convince healthcare providers in India to start using your product. This takes time and money to support your marketing and sales efforts. Additionally, many of the providers may not be as trained as their US or UK counterparts and may be less likely to adopt your product if it requires a certain level of training. Finally, there is the issue of who is going to pay for the product. In India, only about 25 percent of people have basic health insurance so any device in India needs to be quite low cost to be broadly used.

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Neuroscience, Research, Stanford News

A little noise in the brain’s wiring helps us learn

A little noise in the brain's wiring helps us learn

shutterstock_139305437It didn’t come as a surprise to me when I learned from neuroscience postdoctoral scholar Tatiana Engel, PhD, that all of us have a bit of noise in how our neurons fire. In response to the same signal, they’ll usually fire one way then occasionally fire a different way.

I, myself, blame a number of my quirks on noisy and confused neurons.

Engel told me that Stanford Neurosciences Institute director William Newsome, PhD, had discovered those noisy neurons almost two decades ago. He had trained animals to detect whether dots on a screen were moving to the right or left. He found that the way a single noisy neuron fired was also reflected in how the animal categorized the dots – if the neuron indicated right, the animal chose right and vice versa.

In a story I wrote Engel said, “[It]was exciting to me to realize that we are used to thinking about ourselves as agents who are in charge of our decisions and in charge of our thoughts, but the brain might be playing tricks with us.”

Engel recently published work she did in computer models in which she tried to understand why the neurons didn’t fire the same way every time. What she found is that if neurons don’t have a bit of a bias to begin with they don’t learn through a reward system. Essentially without occasionally firing left when the dots are moving right, the neuron can’t ever improve its accuracy.

The type of learning Engel studied is the same kind of learning we use when learning to categorize food into groups we like or don’t like, or to categorize music or even objects. Her work appears in Nature Communications.

Previously: Stanford neurobiologist Bill Newsome: Seeking gains for the brain and Deciphering “three pounds of goo” with Stanford neurobiologist Bill Newsome
Image from Shutterstock

Bioengineering, Cardiovascular Medicine, Stanford News, Technology

Writing a “very specific sentence” is critical for good biodesign

Writing a "very specific sentence" is critical for good biodesign

This post is part of the Biodesign’s Jugaad series following a group of Stanford Biodesign fellows from India. (Jugaad is a Hindi word that means an inexpensive, innovative solution.) The fellows will spend months immersed in the interdisciplinary environment of Stanford Bio-X, learning the Biodesign process of researching clinical needs and prototyping a medical device. The Biodesign program is now in its 14th year, and past fellows have successfully launched 36 companies focused on developing devices for unmet medical needs.

1 After several weeks spent following doctors through cardiovascular disease clinics, Debayan Saha, Shashi Ranjan, PhD, and Harsh Sheth, MD, together identified 315 apparent medical needs ranging from better ways of monitoring patients to improvements of existing devices. During the course of their six-month fellowship, they’ll develop a prototype device to solve just one.

The first step toward picking that one is to better define the 315.

This is more complicated than it seems. For example, one of the needs they’d originally written down involved real-time monitoring of certain molecules in the patient’s blood. They revised that phrasing because it defined the solution – real time – rather than the problem, which is the need for doctors to have more accurate information about the patient’s blood so they can make better treatment decisions. “One solution to the problem might be real-time, but there might be another way,” Sheth said.

Similarly, another need they identified had to do with a device that was inconvenient for doctors to use during a medical procedure. Did they need to improve the device to make a procedure more efficient, or was the need specifically for a smaller device? With another device, they debated whether the real need was to reduce the patient’s pain or to reduce the blood loss.

Some of these decisions might sound like splitting hairs – whether the problem is pain or blood loss, there is a clear need for a better device. But the distinction makes a difference down the road. If they chose to focus on the pain rather than the blood loss, that would effect what insurance will pay for its use and intellectual property – factors that make a difference in whether or not a device can get funding and eventually reach patients.

“We need a very specific sentence to make very clear the need we are trying to solve,” Saha said.

Eventually the team will sort through this list of needs to identify the single focus of the remainder of their time.

One thing I found interesting: In fourteen years of the program, each year with several teams working on the same medical field, no two teams have ever developed devices to satisfy the same need.

Previously: Good medical technology starts with patients’ needs and Biodesign program welcomes last class from India
Photo of Shashi Ranjan and Harsh Sheth on a clinical visit by Kurt Hickman

Bioengineering, Stanford News

Miniature chemistry kit brings science out of the lab and into the classroom or field

Miniature chemistry kit brings science out of the lab and into the classroom or field

KorirA few months ago, Stanford bioengineer Manu Prakash, PhD, and graduate student George Korir were recognized for an ingenious (to me) contraption built from a music box that creates a simple way of doing very small scale chemistry experiments.

That award, from the Gordon and Betty Moore Foundation and the Society for Science & the Public, recognized the device for its possible use as a chemistry set for kids, but Prakash and Korir also see it as useful for scientists in a lab or out in the field.

They’ve now published the device in PLoS ONE , describing its functionality for scientists as well as kids.

The general idea is that this 100 gram device uses a hand crank to wind a long punch card through metal prongs. In its original state, those metal prongs then each played a note on queue. In their reconfiguration, each metal prong releases a droplet of a chemical or controls pumps and valves.

At only two inches in length, Prakash and Korir say the device is easy to carry and could be programmed to carry out chemistry experiments outside the lab – testing water quality or soil samples, for example.

“The platform is simple to use and its plug and play nature makes it accessible to both untrained health workers in the field and young children in classrooms,” Prakash wrote.

This device is part of Prakash’s ongoing focus on frugal science – devices that are inexpensive and functional enough to bring science out of the lab and into the world. He previously developed a 50 cent microscope called the Foldscope that is being used by groups worldwide to investigate their environment. Some of the images taken through the Foldscope can be viewed here.

Previously: Music box inspires a chemistry set for kids and scientists in developing countries and Foldscope beta testers share the wonders of the microcosmos
Photo by Kurt Hickman

Bioengineering, Cardiovascular Medicine, Medical Education, Research, Technology

Good medical technology starts with patients’ needs

Good medical technology starts with patients' needs

biodesign fellows

This post is part of the Biodesign’s Jugaad series following a group of Stanford Biodesign fellows from India. (Jugaad is a Hindi word that means an inexpensive, innovative solution.) The fellows will spend months immersed in the interdisciplinary environment of Stanford Bio-X, learning the Biodesign process of researching clinical needs and prototyping a medical device. The Biodesign program is now in its 14th year, and past fellows have successfully launched 36 companies focused on developing devices for unmet medical needs.

The first step in solving a medical challenge is identifying a problem in need of a solution. This seems intuitive, but often people start from the other direction – they’ve developed a technology and go looking for some way to apply it.

Learning that workflow is one thing that brought Shashi Ranjan to the Stanford Biodesign program from Singapore. “I was making devices but didn’t see them going into people,” he told me. “I wanted my technology to go into the real world.”

As the fellows encounter patients and doctors, they are compiling a list of existing medical needs.

Ranjan, along with Harsh Sheth, recently visited the Stanford South Asian Translational Heart Initiative run by Rajesh Dash, MD, PhD, to witness first-hand cardiovascular needs encountered by South Asians in the Bay Area. (The third member of their team, Debayan Saha, was at a different clinic that day.) After observing some patients, what became clear to the two is that lifestyle changes are a major barrier to improving cardiovascular disease risk in South Asians, just like in any other population.

Some of the problems they encountered appear obvious: How do you help people get more exercise and maintain a healthy weight? Develop a device to solve that and the team would help many more people than just patients with cardiovascular disease.

The two had also observed that many people who are overweight have sleep apnea, or short pauses in breathing during sleep, which can contribute to heart disease risk. The devices that exist to help sleep apnea look like cumbersome gas masks and aren’t conducive to a restful slumber. Several patients they observed don’t use the device regularly despite knowing that it could lower their risk of having a heart attack.

After observing patients, the pair added to their growing list of 300 plus medical needs a better air mask for sleep apnea, along with simplified screening for people who are at risk of heart disease. Patients at Dash’s clinic are asked to make routine visits for specialized bloodwork and other screenings. “Can we make the tests simpler but still effective, and available at the point of care?” Sheth asked.

I asked Dash why he wanted to work with Biodesign fellows like Ranjan and Sheth – their presence in the office visit certainly made the room tight and patients perhaps a tad uncomfortable. He told me that training people to make better medical devices is critical to providing good care.

The fellows from India are particularly valuable he said. “They learn how we are approaching the problem here then help find solutions that are effective in India.”

Over the next few weeks, the team will stop visiting clinics and will begin the arduous task of narrowing down their list of more than 300 observed medical needs to the one that will become the focus of their fellowship. (Four other teams are going through a similar process, and they’ll all present their prototypes at a symposium in June.)

Previously: One person’s normal = another person’s heart attack? and Biodesign program welcomes last class from India
Photo, of Shashi Ranjan and Harsh Sheth observing as Rajesh Dash, MD, meets with a patient, by Kurt Hickman

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