Putting light to work in virus and cancer detection, retinal disease, brain research
By Barbara Moran
A playful artwork titled “…on the shoulders of giants.” —Sir Isaac Newton dominates one wall of Boston University’s Photonics Center lobby. Colored balls of light dance on the screen, bouncing, then floating, then bouncing again. Students and faculty often stop, mesmerized. The art sends a clear, if surprising, message: Hey, photonics is cool!
No one embodies this spirit more than Thomas Bifano (ME, MSE), the energetic and enthusiastic director of the Photonics Center for the past seven years. Bifano champions the field of biophotonics, where scientists work at the intersection of biology and engineering to investigate viruses, turn brain cells on and off, and examine the human eye.
As a College of Engineering mechanical engineering professor, Bifano’s own research concentrates on adaptive optics—adjustable mirrors that change shape to focus light in telescopes and medical devices. A professor for over two decades, Bifano was the ENG manufacturing engineering department chair from 1999 to 2006, and the college’s 2013 Distinguished Lecturer. He likes to point out that both positions came with actual chairs. “If I can get four more,” he says, “I’ll have a dining room set.”
BU Research spoke with Bifano recently about what goes on inside the Photonics Center.
BU Research: A lot of people walk by this building and they think, photonics? What’s that?
Bifano: Right. And it’s funny because everybody knows what electronics is, but nobody knows what photonics is. And really, photonics is the use of light for some practical purpose, just like electronics is the use of electricity for some practical purpose. Electronics is having electrons fly around in certain patterns and shunting them hither and yon. Photonics is the same thing using light.
Everybody knows about electronics because everybody has a stereo.
But everybody has a DVD player, which is all photonics.
I think you need to do some photonics branding.
Yeah, there you go. The problem is that photonics is a relatively diverse field, and it would be hard for a layperson to say how it’s impacted their lives. But all data transmission—all data transmission throughout the world—is fiber optics. It’s a huge impact on our lives. All of the Human Genome Project was optics. It was only optically that we were able to detect the A, G, Cs, and Ts in the genome. I could sit here all day and give you examples.
The center has done some interesting work on virus detection—can you explain that? What do viruses have to do with light?
We do a lot of work in infectious diseases at BU. And people had been working on how to detect a virus, which is much smaller than bacteria. The chemical way to do that is to make the virus attach to something very large and very easy to detect: a fluorescent particle. And then I can see the virus because it’s been tagged.
But one of the things that’s interesting in photonics is that we get to think about things that are very small. The wavelength of light is fractions of a micrometer. The size of the virus is fractions of a micrometer. There’s actually a wonderful marriage between those length scales. So ENG Professor Selim Ünlü (ECE, BME, MSE) and ENG and College of Arts & Sciences Professor Bennett Goldberg (Physics, BME, ECE, MSE) figured out that if a virus attaches to a surface, it will make the surface slightly taller. And by being slightly taller, they could detect that change with exquisite precision. So they were not only able to detect single viruses; they were able to say what they look like.
It’s so interesting. I always thought of photonics in the realm of fiber optics and DVD players, but using it for biology makes sense, because it’s on the same length scale. And with molecular biology merging with engineering in so many ways now, you see all these possibilities to use light not just to observe biological systems, but to manipulate them.
Absolutely. Thank you, that’s a great introduction for where I’m going next. So we decided at some point: let’s pick a topic and build a collaboration with business where we can translate our research to something of value to society. And we chose the area of biophotonics for that. Biophotonics is just like it sounds. It’s the use of light to enable some kind of biological measurement or treatment, exploiting the fact that many biological materials react to light in very well-known, easily measured ways. Each year we run four or five projects through our Industry/University Collaborative Research Center and have an annual colloquium and seminar.
Can you give an example of one of the current projects, or is it secret?
No, I can give you an example. One of the projects is led by ENG Professor Jerome Mertz, in biomedical engineering, and he invents new techniques of microscopy. And he was given the task: can you develop a new technique that will enable us to see cells that are passing at very high speed in a cell-sorting device?
Why are you sorting the cells?
Suppose you have a cancer cell—
So they’re trying to get a cancer count?
Well, that would be a great example. If you’ve had a metastasis and you want to know if cancer cells are in your bloodstream. But there are all sorts of reasons you would want to measure particles flowing by very fast in a biological system. And so the problem is that generally, with high-precision microscopy you have a very narrow depth of field. You can’t see very far. And so Mertz developed a technique that can extend the depth of field while maintaining the resolution. So that was beautiful.
That kind of thing would knock your socks off—if you’re used to seeing things at a certain depth of field or resolution and suddenly it takes a huge leap forward.
The other thing I wanted to talk about in the biophotonics world is that if you look at the pillars of strength in research on the Charles River Campus, photonics is one. Another one is neuroscience, and yet another one is bioengineering. What’s at the intersection of those three? The brain. There’s a wonderful new field in brain science called optogenetics. It’s the idea that you can tag photonically active proteins to neurons, and that gives you a control system. So suddenly, for the first time ever, we have the capability to not only measure what’s going on in the brain optically, but also to control it optically. So this is a wonderful, exciting new field.
It seems this sort of research would have been impossible 15 years ago. There’s been this leap from being able to just observe the brain to what is now possible.
It’s funny, because I didn’t think we were going to talk about the brain at all. I thought we were going to talk about telescopes.
Oh, I can talk about telescopes.
This is much more exciting. But is there a connection between the work you’ve done with mirrors and telescopes and this new work in biophotonics? Somehow it seems different.
I’ll give you a connection. So in telescopes you have this huge problem. To look out at a star from the ground, you have to look through this soup of atmosphere. So if I start by sending a plane wave out from here, by the time it gets through the atmosphere, it’s kind of wiggly. And similarly, coming from the star, the light gets wiggly on the way to the telescope. The idea is that if you can measure that effect of the atmosphere, you can fix it. My whole research life has been about making mirrors that fix it.
Now every telescope that’s worth its salt has adaptive optics, and it works really well. And then the scientists said, “Okay, so that allows me to get a beautiful image of a star. Let’s try to find a planet around the star.” Well, if you think about that, it’s ridiculously small and the star is a billion times brighter than the planet. And the atmosphere’s still screwing you up. It’s a hopeless optical problem.
And so they came to BU and our spinoff company, Boston Micromachines Corporation, to make that mirror. And we made that mirror, and put it into an instrument that went to the Gemini Planet Imager in Chile, and now all of a sudden you’ve got the best images ever of planets around stars.
How big is the mirror?
This is the mirror we put in.
This little thing on the table? It’s so small, like a big postage stamp.
This is exactly the one. So the telescope is the size of the room. This is the secondary mirror. The big mirror collects all the light, it goes down to this one, this fixes it. It’s done.
There’s a comparable problem in trying to look at your retina. All the major eye diseases are diseases of the cells in the back of the retina. The cells of interest are photoreceptors—cones and rods—and it turns out, sadly, that the blood vessels in your eye are in front of your photoreceptors. Why? What was God thinking? It’s the wrong design. I want to file a complaint.
It’s a worse optic than you could buy off the shelf, let’s just say. So the physician can’t see the cellular structures in your eye. They just see a gray mishmash.
Is this because of the shape of the eye or because of the fluid inside?
No, it’s the shape. It’s totally the shape. So what people did was develop instruments that did exactly what the telescope did, adjust for the aberrations of the eye.
And when I think about these two impacts that the technology coming out of my lab has had—one in astronomy, finding planets, answering the big fundamental question “Are we alone?” and the other helping people cure retinal disease—I’m drawn more toward the retinal disease. It’s messier, it’s uglier, the patients are sick. They don’t want to sit in front of an instrument for 10 minutes. So it’s complicated. But in another way, I think this is a place where we make a big impact.
Barbara Moran (COM’96) is a science writer in Brookline, Mass.