Category Archives: biophotonics

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Everyone knows what a Tricorder is supposed to do; Star Trek’s cultural influence has spread far and wide. Designing a device that could actually do the job is another matter entirely, although the people behind the Qualcomm Tricorder XPRIZE had enough faith to put up $10 million as an incentive to pull the idea further towards reality. One hand-held system that’s definitely along the right lines is called the Cyclops, and uses LEDs to shine different wavelengths of light onto an unknown substance and rapidly analyse the reflections it gets back. For now it’s limited to surface and only slightly sub-surface analysis, but it turns out there’s a lot you could do with just that functionality, and developers Visualant are working on ways to build into a medical probe too. I interviewed their CEO about it, and what the ramifications might be.

Biophotonics is a growth area and likely to stay that way for a while, especially at places like University College, London, which is becoming one center for UK research in the field. I wrote about three of their projects for Optics.org, including some near-infrared imaging technology that’s already left the lab; and more on that potential use of optogenetics to switch off epilepsy, an approach where the regulators will need some further convincing.

Vision on

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Some eye diseases have a nasty habit of being all but untreatable by the time the patient is aware of the symptoms; a dirty trick on the part of the designer. Age-related macular degeneration is one, but AMD spends a long time brewing in the tissues of the retina before making itself known as actual vision loss. Now it turns out that it might be detectable during that gestation period, through a simple test of how a patient’s eyesight adjusts to darkness. I wrote about that test for Optics.org.

Also in the eyesight department: retinitis pigmentosa is being tackled through electronic implants of two different types, the epiretinal and subretinal varieties. Each sits in a slightly different position in the retina and does its job in slightly different ways; neither is guaranteed to succeed nor to be hassle-free for the patient. Intriguingly, the two approaches ultimately stem from a fairly fundamental difference of opinion about what AMD does to the retina.

Robotic surgical systems are becoming more advanced all the time; the top-of-the-line ones already have a distinct air of science-fiction production design about them. The overlap with the equally rapid advances in biomedical imaging techniques seems obvious, but the synergies are not materializing as fast as you might think. I spoke to Intuitive Surgical to find out why, and what benefits will follow once the two camps get in sync.

And: a report from a conference on biophotonics held at University College, London. Among other things discussed, a potential use of optogenetics for turning epilepsy off in the brain as soon as it starts to manifest itself.

The right horse

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I spent the first week of February in San Francisco; some of it looking at Alcatraz Island and pondering the best bits of Point Blank, which is all of them, but most of it deep in the warrens of the Moscone Center while the Photonics West trade show was held upstairs. Among other things I was there to help write the show’s daily newspaper and sit in on some of the technical conference sessions, a job which always amounts to a crash course in the state-of-the-art of five or six different inter-connected industries. The fruits of that will feed through for a while in one form or another; here are a couple of the early results.

It’s not news that Raman spectroscopy should be able to spot malignant tumours in early stages of development and be a real boon to cancer diagnosis, but it will definitely be news when it becomes a practical clinical proposition. Vancouver-based Raman specialists Verisante won an award in San Francisco for its Aura probe, which looks like it might be the answer for skin cancer, and a version able to be used on internal cancers in the lungs and bowel is being trialled now with FDA approval on the agenda. I interviewed Verisante’s CEO about it, and the advantages of Vancouver as a location for effective cancer research. Among the things cut for space was the fact that he spent considerable time and money trying to make terahertz technology work in this field, before realising that he was backing the wrong horse and switching to Raman instead.

Bioimaging is booming, since the technology is at that stage of development where each incremental step opens up numerous potential applications. But the keyword is “potential”, and the inherent risk is that clinical usefulness gets left behind in the rush forward, with the technology delivering more and more information and the scientists having less and less idea exactly where it comes from. This sentiment was articulated neatly by Bruce Tromberg from the Beckman Laser Institute as being “the really beautiful but also somewhat horrifying thing about this field.”

And I interviewed Paul Thurk, a venture capitalist from the US now based in Ireland, about the cultural differences in his line of work that pertain on either side of the Atlantic. Turns out there are plenty, not just in things like employment law and pension plans, but also in peoples’ attitudes to those sort of topics too. This is far from trivial when it comes to successfully prodding a promising technology forward on an international stage and not having the enterprise crumble in your hands. The interview is in the third issue of the Photonics West daily publication, which for now is only available here as a pdf download, but the topic will be back.

Weather men

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Two days in Bordeaux at an investment conference duly produced two published pieces, one on the current state of biophotonics markets and one doing a similar thing for cleantech.

A capricious mix of optimism and nervous glancing at overhead thunderclouds has become the new standard in both sectors. Folks connected with LED lighting predict a revolutionary couple of years ahead, while delegates from the solar sector mostly looked like a revolution had just run them over with a steamroller. The future course for biomedical optics looks certain; an aging population in need of ophthalmic surgery will help take care of that, especially once the high-volume consumable items associated with the procedures are properly incorporated into the value chain. But the circumstantial evidence suggests that for now no one involved is actually making much money.

Not shown: a graph predicting that by the end of 2015 there will be two working IP devices for every person on the planet, all down to video streaming, machine to machine traffic, and device to device communication. Also not shown: the other graph indicating that the current capacity of data networks is nowhere close to handling that kind of avalanche effectively.

“The carrier’s business model is broken,” said Ian Jenks, whose company Intune Networks is in the network virtualization business and whose presentation could have come with a klaxon, if the message wasn’t becoming familiar from other quarters too. “By the end of 2013, the cost of transmitting one bit of data will be greater than the revenues received for doing so.” In this case the cloud brings not just a silver lining but the route to salvation.

Vision things

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Two holdovers from my trip to Baltimore for SPIE DSS 2012 have appeared on Optics.org:

Since shining a laser pointer in the general direction of an aircraft pilot seems to be the jape that won’t go away, optical filters that can limit the dazzle are in demand, and the military are just as interested in them as commercial airlines – probably more. Filters usually work by blocking the particular laser wavelengths used in your average pointer, but a better approach might be to block incident light based on its power instead. KiloLambda showed off a wide-band filter that uses a layer of carefully manufactured nanostructures and exploits their non-linear optics to block laser light when it passes a designated power threshold. Below that, the filter stays clear at all wavelengths; above it, transmission is either limited to a certain value or blocked completely.

Nanstructures are also the key to a scintillator material made by the applied research arm of Georgia Tech, a cerium-doped gadolinium halide material cast in a glass that scintillates when hit by incoming gamma-rays. If the nanoparticles used can be held below a certain size, and about 20 nanometers or so seems to do it, then the scattering of the scintillated light which can bedevil any kind of accurate reading is drastically reduced. Plus a glass or glass-ceramic material is much easier to handle than a fragile scintillation crystal. Plenty of room for improvement in the resolution, though.

And away from DSS: further work on retinal implants, a topic that has now entered the watch-lists of TV news producers everywhere. The principle of restoring sight to someone suffering from a condition like age-related macular degeneration hinges on the fact that it’s the photoreceptors in the retina that have died, not the neurons behind them. Implants to take over the job of the receptors and fire the neurons when light hits the retina are well past the status of pipe dreams, but there are a wealth of problems – not least among them, how to power the array of photoreceptors while it goes about its business. A group from Stanford University, applying scrupulous logic, think the answer may be to build an implant which draws its power from the same incoming infra-red light which brings the visual data, and their lab trials suggest that they’re on the right lines. Not quite a solar-powered retinal implant, but not too far off. Not a bionic eye either, although Steve Austin is the gift that keeps on giving for headline writers on a deadline.

Military-industrial complexities

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A week in Baltimore at SPIE’s Defense Security and Sensing conference on behalf of Optics.org produced a few published things.

Among them, coverage of an address from Bruce Carlson, director (possibly former, by now) of the National Reconnaissance Office. Viewed by a visiting European, the back-and-forth over funding and priorities within the US intelligence community is endlessly fascinating. But I hadn’t realized that the NRO also tracks orbiting satellites and takes action when there’s an imminent collision among all the circling hardware. A man who can say “Every other week or so I manoeuver a satellite around”, is one with an interesting desk. As you might expect when the holder of this post addresses an open meeting of international delegates, there was a certain amount of frostiness in the air; forty-two minutes in, someone asked a question about the potential usefulness of the NRO’s info to human rights organizations, and Carlson more or less adjourned the meeting on the spot.

Also a keynote from Franca Jones of the White House science policy office, who made the point that there’s room for much more joined-up thinking when it comes to gathering data on climate and habitat, and a clear connection between having that kind of info on hand and the ability to predict things like cholera outbreaks. Biosurveillance still has an almighty image problem though, starting with the word; expect “biosensing” to feature in a larger font.

And a discussion between military strategists and venture capitalists about why the military needs new kinds of infrared sensing technologies. It is still jarring, nearly eleven years after the game most visibly changed, to hear a man from DARPA comment that “our mission is changing, but our sensor technology is not,” although here too you wonder if the discussion would have been quite the same behind closed doors and away from international observers. None the less, the sentiment that changes in warfare can be good for the progress of technology and the balance sheets of private companies is hard to argue with, even while quietly wishing for a different kind of world.

Numbers game

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the delicate work of stem cell injection. photo: J. Michael White, Washington University School of Medicine.

One of the more modest notable features of stem cell research is the contrast in numbers. Researchers perform precise and exacting microsurgery on individual cells, prizing minute openings in the membranes of eight-cell embryos so that stem cells can be introduced through the gap. And to prepare, they carry out large-scale housekeeping operations on cultures containing millions of cells, ablating and scoring and where necessary destroying them in bulk. The pattern holds for fertility studies and IVF too.

If the same basic kit could do both kinds of operation, things would not only go faster but be cheaper too. Hamilton Thorne has designed a family of microscope objectives that incorporate miniaturized laser diodes but still fit into standard laboratory kit. Pick the right one, and your microscope has just acquired a laser powerful enough to do the housekeeping or delicate enough to do the prizing.

My chat with the company for Optics.org about the goal of making lab-scale eye-safe lasers a practical proposition for cell biologists, and the small matter of a $1.3 billion market sector to be tapped, is here.

The fog lifts

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Here’s a helpful thought for anyone squeamish about cataract surgery: Apparently it goes back 4000 years, when in all likelihood your chosen practitioner advanced towards you with pins, splinters and a prayer. The modern approach seems more palatable.

But it’s still not terribly subtle. An incision through the lens’ surrounding capsule lets an ultrasonic probe get into the meat of the lens, and liquify it so it can be flushed out. That’s a blunt attack compared to the finesse possible with an ultrafast laser, which can score neat patterns and planes into the lens and assist it in falling to bits with less collateral damage or heat effects. The same laser can also make that initial cut in the capsule, which is reckoned to be the most delicate part of the procedure. And as it happens, femtosecond lasers are already a common sight in opthalmology clinics thanks to LASIK surgery.

Four developers have joined the dots and produced femtosecond systems for cataract procedures, which are working their way through the regulatory approval process. One company has now been bought by Alcon for $361 million in cash and the carrot of another $382 million if things go well, so the sector’s fuse might be burning. The only European player currently is Technolas PV, who do indeed supply LASIK kit already, and told Optics.org why taking aim at cataracts makes sense.

Mapping eye disease with LEDs

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Now posted at Medicalphysicsweb: A team including Nick Everdell from University College London fitted LEDs into an existing fundus camera to take multispectral photographs of the inside of the eyeball.

Using LED sources at carefully controlled wavelengths allows researchers to accurately plot the distribution of light-absorbing chromophores in the interior of the eye, potentially giving earlier warning of diseases like diabetic retinopathy and age-related macular degeneration.

The conventional approach is standard RGB photography, which gives you an actual photograph of what’s in there but not one that can differentiate the different molecules of interest particularly well. The LED method is authentic multispectral imaging, which means that number crunching is needed to disentangle the data afterwards, but which eventually gives up a probable distribution map of the individual critical species. Plus it pulls in its data fast enough that involuntary eye movements (or microsaccades, my second favourite ophthalmology term after “zonules of Zinn”) don’t interfere.

They retro-fitted the LEDs into a 20-year old Zeiss machine for the test flight, since modern fundus cameras are packed with electronics and circuitry that just got in the way. Never throw out the old kit.

One small heart

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“…and a great big soul that’s driving.” (Mary Chapin Carpenter.)

An infrared laser can delicately pace the beating of a quail embryo’s heart, the first time the technique has been shown to work with an intact heart and without causing damage.

Full story over at Physics World. (edit to add: also picked up by Medicalphysicsweb.)

UPDATE: Nicholas Smith at Osaka University, whose team first demonstrated in 2008 how ultrashort laser pulses could induce contractions in cardiac muscle cells and so took a big step towards possible optical pacemaking, kindly sent me some thoughts on this topic.

He confirms that, although much is understood about the fine details of cardiac activity, there is still plenty of uncertainty left. The US team in the new study think that thermal effects generated by the laser could be the key to why it initiates a heartbeat, but other factors could be in the mix too.

“It’s well known that the equations describing membrane equilibrium are temperature dependent, and if all ion channels across the whole heart (such as sodium channels, but potentially others) suddenly undergo a transient change in permeability, then that could kick the heart into beating at the periodicity of the laser irradiation,” Smith says. But equally, “the new work uses a wavelength of 1.875 microns, which can be absorbed with reasonably high efficiency. So perhaps it’s the wavelength which is most significant, allowing low-power irradiation to have efficient interaction with the sample.”

Assuming that you start with the right wavelength, and around 2 microns seems to work, then it could be just a matter of supplying the right amount of total intensity at the right time, gated so as to generate a pacemaker signal. This perhaps need not be from a laser at all. As Smith notes, laser diodes are already fairly compact, but if you could generate sufficient power from an LED at 1.875 microns, you might be able to produce an implanted pacemaker using an LED instead.

The topic is formidably complex, though.

“One of the main barriers to knowing what’s going on is that you are looking at a fairly indirect connection between laser light and effect,” says Smith. “In our research, we observed (and expected) that laser light would cause muscle cell contraction, but the interaction is a multi-step process: light irradiation, followed by 2-photon absorption, then generation of excited and reactive species along with heat, leading to various changes in cell structure and permeability, affecting the calcium levels in the cell – and then contraction.

“In the new work by Jenkins et al it’s probably slightly simpler, due to the single-photon absorption, but there are many stages involved and some of them are nearly impossible to monitor properly. This is the main barrier to understanding what happens. We made good headway into following how the light affects the cell, but the complexity in the interaction chain means it’s hard to isolate and identify each step.”