New Micro-Microscope Is Portable And Cheap Scientists at Caltech have created a tiny, lens-free microscope that they say could be built for just $10. Changhuei Yang, one of the microscope's inventors, explains the device and some of its potential uses.

New Micro-Microscope Is Portable And Cheap

New Micro-Microscope Is Portable And Cheap

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Scientists at Caltech have created a tiny, lens-free microscope that they say could be built for just $10. Changhuei Yang, one of the microscope's inventors, explains the device and some of its potential uses.


This is Talk of the Nation: Science Friday. I'm Ira Flatow. Up next, a really interesting connection between the floaters in your eyes. You know how you look - you're lying in the grass, you look up at the sky, and you see these floaters, cells floating around in your eyes. Well, that sight led to the invention of a new kind of microscope, a tiny, teeny, little microscope, and it had its origins there. It's a really interesting story. But I'm getting ahead of myself, because I'm very burying the lead.

Let me give you the lead, as they say, of the news, and that is researchers at Caltech have invented this microscope that's so tiny it sits on a computer chip and the whole device could fit on your finger. And it does away with the bulky and expensive lens of a microscope in favor of a design that directly projects the image onto the computer chip. And having a tiny, portable microscope, a cheap one that, you know, could be made for just a few bucks, could change the way healthcare is done in poor countries, and almost in the most sophisticated science labs, around the world.

Joining me now to talk about this microscope, described in this week's proceedings of the National Academy of Sciences, is one of its inventors. Changhuei Yang is an assistant professor of biology engineering and electrical engineering at Caltech in Pasadena. He joins us today from the campus. Welcome to the program, Dr. Yang.

Dr. CHANGHUEI YANG (Electrical Engineering and Bioengineering, California Institute of Technology): Thank you, Ira, for having me on the show.

FLATOW: Well, you're quite welcome. Describe to me this - the connection between the floaters...

Dr. YANG: Sure.

FLATOW: And your idea here.

Dr. YANG: OK. So, if you actually look at a conventional microscope, there's a lot of lenses in there, and if you look at the design of the microscope, it has been around for a few hundred years now, but has hardly changed in its fundamental design over the years. It turns out that it's actually very difficult to try to miniaturize that so that it can fit compactly onto a chip. And one of the reasons for that is because there's so many optical elements on it that is very difficult to miniaturize in an inexpensive fashion.

So, after we took a look at the problem, we decided that, you know, if want to actually miniaturize the microscope, we've got to do it another way. And that's why we drew inspiration from floaters in our eyes, which tells us that you really don't need all those fancy lenses to do imaging. All you really need is to take the object of interest and put it very close to the sensor chip. And as long as the density of the sensor chip is high enough in terms of its pixel density, you should be able to do imaging that way.

FLATOW: Hm. Sort of like - because the floaters are behind your lens. They're not being focused on your retina. They're basically just being - bumping up against your retina.

Dr. YANG: Exactly. And in fact, this is actually a very interesting experiment to try, which is the next time you see floaters, try removing or putting on your eyeglasses, and you'll see that the floaters remain equally clear.

FLATOW: Hm. And so now, that means that the - if your retina, which is sensitive enough, and the floaters are on top of it, you try to recreate sort of putting a sample that's like the floaters on top of a chip like your retina.

Dr. YANG: That's right. The only problem with that is that what is commercially available, that - the chips are commercially available, they just don't have the pixel density that is high enough to actually be able to do this well.

FLATOW: Right.

Dr. YANG: So, we came up with a way to effectively increase the pixel density by using very small holes that are punched onto a layer of mantle that we have coated onto the chip itself.


Dr. YANG: And in that case, the holes itself sets the resolution. So, the actual device is very simple. All we do is put in a micro-fluidic channel on top of this array of holes, and then we take the object of interest and flow it through this micro-fluidic channel. And as it passes across the holes, each individual hole effectively acquire a light scan of the object. And all we do at the end of the day is simple stack up all these light scans and create the high-resolution image.

FLATOW: 1-800-989-8255 is our number. Talking with Dr. Yang here, talking about this new kinds of microscope. So, would it be fair to say that the more little holes you have in there, the higher the resolution, or the greater the pixel density, or what we call, like in a camera, you have high resolution?

Dr. YANG: The resolution, in this case, is set by the size of the holes.

FLATOW: Mm-hm.

Dr. YANG: So, as the holes get smaller and smaller, we can actually get finer and finer resolution. The number of holes actually gives us the effective field of view that we are looking at. So, let's say, if we're looking at a relatively big cell that's 50 or 60 microns, you might need more holes than compared to if you're looking at a cell that is 10 microns in diameter.

FLATOW: Mm-hm. And so what kind of magnification are we talking about here?

Dr. YANG: OK. So, effectively, what we are - comparable to a 10x or 20x microscope at this moment in time.

FLATOW: And what would you do with such a small magnification?

Dr. YANG: Actually, you can see yourselves quite well using this approach, and we actually have been working with biologist who wants to do automated imaging of microorganisms, and this fits very nicely in that context because the imaging that we're doing is done in an automated fashion. So, they can effectively simply drop in the solutions containing the objects they want to look at and then come back in a couple of hours or a few minutes and simply collect the images that way.

FLATOW: Interesting. So, whatever you're looking at, it has to be in a fluid.

Dr. YANG: That's right. But then again, if you look at what is commonly found in bioscience experiments and the samples that clinicians analyze, a lot of it is already in fluid form. And right now you actually have to plate it on to a glass plate before you can examine under the microscope.

FLATOW: So, could you look at blood cells?

Dr. YANG: Oh yeah, absolutely. And in fact that's actually one of the things that we're particularly interested in doing right now, which is to actually use this to look at malaria parasites in blood samples that we collect.

FLATOW: And so, you could then make this cheaply enough that you could produce this on mass and then take this out to poor countries where people are having trouble with parasites?

Dr. YANG: That's right. That's one of the things we are hoping in terms of being able to view a rugged iPod sized device that contains one of this microscope. It's actually interesting to note that the microscope is about the size of Washington's nose on a quarter and we need a relatively large iPod size device simply because you need a screen to be able to display the images that we acquire. So, the microscope is really a very tiny part of the (unintelligible) that we're talking about here.

FLATOW: So, you could take one of these tiny little chips and maybe take a USB plug and plug it into your iPod or something and look at it?

Dr. YANG: Well, yes exactly. That's one way that you can use it. You can plug it into your computer or you can simply have it so that it incorporates into the iPod-size device and it allows you to actually see the image directly projected.

FLATOW: 1-800-989-8255. How inexpensive can you make one of these?

Dr. YANG: So we expect that at the end of the day when we start manufacturing these on a semi-conductive fabrication line, that the cost would be about 10 dollars. And the way we came up to that estimation is because the off the chip - off-the-shelf chips that we're using right now cost about 20 dollars when we buy it on a retail level and that's probably a huge mark up on that price as it is.

FLATOW: And what about using water quality, not just blood but stuff that might be in the water?

Dr. YANG: Oh yeah, absolutely. And which is another reason why we think this is useful for double applications because you can start to think about building a device that is multifunctional. You can use it to look at blood samples, you can use it to look at urine, look at water quality to check for harmful bacterias.

FLATOW: Can you make one that doesn't need the fluid?

Dr. YANG: That's possible. In that case you would want to be scanning your sensors across the object. The reason why we haven't pursued that much is because typically the samples that we're working with is already in fluid form and it's just easier to scan the object fluidically than to try to scan the sensor.

FLATOW: You know, because why I'm asking, I'm thinking about every cellphone has a camera on it now.

Dr. YANG: Right.

FLATOW: Why not put a microscope on the cellphone?

Dr. YANG: Oh, absolutely.

FLATOW: Won't that be fun? Have a microscope on your cell phone?

Dr. YANG: Oh, yeah. Absolutely. And actually it has potentially a good - it's actually a potentially very good way to protect against bio-terrorism. Because if you think about this, the cost of actually us putting something like this on a cell phone might cost about a dollar since it already contains a camera which is typically underutilized anyway. You don't use it 24 hours a day anyway. So, you can potentially have one of those - one of our device implanted on to your camera on the cell phone, and simply have it passively check for harmful things that might be floating in the air. And if anything is picked up that way it would actually alert you to the fact that, you know, something might be going wrong.

FLATOW: Well you see, you're thinking like a military application, because I'm thinking of the stuff for kids for me. I want to look at a bug, you know.

Dr. YANG: Oh, yes. Absolutely.

FLATOW: I want to look at a leaf, something like that. Think of all these, you know, how much value that would be for just having fun and being an educational tool.

Dr. YANG: Oh, yeah. Absolutely. Being able to sell this cheaply, I think would really open up a lot of access to educational use as well. So yes, definitely that's one very good application.

FLATOW: I would love to have, you know, you sit there at the table and look at stuff on the table, you know, your own fingerprints and things like that. And kids getting their cell phones at such young ages and they can have a little microscope on the bottom of this.

Dr. YANG: Oh, yeah. Absolutely. And you know what, in a couple of years when we have this done on the (unintelligible) light, I'll send you a prototype so that you can take a look at it yourself as well and evaluate.

FLATOW: I'm ready.

(Soundbite of laughter)

FLATOW: I want my next iPhone to have this thing on there. Steve, are you listening on what we want on the next iPhone? Let me get a caller through at 1-800-989-8225. Dan in Duluth, hi.

DAN (Caller): Hi. I just have a quick question about how exactly this thing will work. So, if you've got a regular, you know, when I was in fourth grade looking at a microscope that you put the little sample on the glass plate and there's a light underneath or a reflective sunlight of some sort. So, if you have this little microchip, do you actually put it on the thing that you're looking at? Like can you put it right on your skin and see an image or do you have to have light behind it?

Dr. YANG: So, that's a good question. So, the way we typically operate our system right now is we take a solution containing the object of interest and inject that onto this chip itself and then the chip actually contains a electrodes - set of electrodes that would electrically drive this fluid across the sensor. And then the light intensity that we use is actually comparable to sunlight so we could actually go out during the day and simply operate the device as it is without the use of any external light sources.


DAN: I love the idea.

Dr. YANG: Oh, thank you.

FLATOW: Great idea. 1-800-989-8225. Let's go to Robert in Grand Rapids. Hi, Robert.

ROBERT (Caller): Hi. How are you?

FLATOW: Hi, there.

Dr. YANG: Hi.

ROBERT: Hi. My question was is there a possible way of automating this system so that you could actually scan for viruses or bacteria to identify them without having to actually physically look at the virus itself. I mean, every bacteria and virus kind of has its own almost fingerprint to it. So, could you automate it in that kind of a way?

Dr. YANG: Oh, absolutely. So, that's actually one thing we're driving our research in which is to actually create - it's actually autonomous as it is. That the problem right now is that we get a bunch of images but the computer is not smart enough now to actually recognize what is what. So, it's typically outputted so that we can actually take a look at it and analyze it the way that you would actually look under a conventional microscope at what is going on. Definitely, I think getting an algorithm that is smart enough to actually do the analysis, it's something that's doable. And it's certainly something that we would like to pursue. Actually, coming to this point, I also would like to point out the fact that because the actual device is very tiny, we can even start to think about putting not just one microscope on the chip, we can start to put tens or even hundreds of this on the chip. And that really actually allows us to do parallel processing and process a lot of samples at the same time. And this is actually very useful for bio-scientists because they may have a lot of samples that they want to process and this would really cut down the time that they would need to spend.

FLATOW: Wow. We're talking about this tiny little new microscope, this hour, Talk of our Nation Science Friday from NPR News. Still in the developmental stage, just thinking out loud. Could you implant this in someone in the hospital or someone who needs their blood monitored for things that might show up?

Dr. YANG: Yes, definitely. Again, that's another line of research that we are actively pursuing with collaborators.

FLATOW: Where are you getting all the money for this?

Dr. YANG: Actually, right now, funding is kind of tight. So we're getting our fundings for NIH and NASA. Actually, our Coulter Foundation which was set up by Coulter was very helpful in terms of getting us started on this. And also, (unintelligible) another funding source was DARPA, which actually was the one that initially...

FLATOW: DARPA, I can understand, yeah. The military's. Let's go to Mark in Silicon Valley. Hi, Mark.

MARK (Caller): Hello. Hi.

FLATOW: Hi, there.

MARK: Yeah, I wanted to comment that this tickled my memory about something I read in Make Magazine and there's basically a weekend project you can do at home if you're interested in doing it on an amateur level. Well obviously, it doesn't have the finesse that you guys are working on. But you can do this with an old, you know, video(ph) recorder that's laying around and so, if you search for Make Magazine lensless microscope, that's how you'll find it.

FLATOW: All right. Thank you.

Dr. YANG: I see.

MARK: Bye.

FLATOW: Thank you very much. So where do you go from here? I mean, we have so many potentials, right? So many potential uses for this.

Dr. YANG: So, we're very excited to start working with one of my clinician collaborators who is very interested in looking at circulating tumor cells. So those are cells that have broken up from a primary tumor and that's the thing that actually goes around and spread the tumor to other locations in the body. So, being able to actually track and measure that is very important to him. And we think that within, you know, maybe not within the next 10 years, but 15 or 20 years from now, we can start to actually have a device that do the analysis and look for all these rogue cells in the bloodstream itself that we would - the device would be implanted into a person. And this will be very useful for them because they can then track continuously for the presence of these rogue cells.

FLATOW: What about just in laboratory situations where you need - you have lots of blood cell samples to look through?

Dr. YANG: Yes.

FLATOW: Would something like that, would work with your microscope work here?

Dr. YANG: Oh, yes. Definitely. And there's actually two reasons for doing this. One is the fact that we can then start to provide point-of-care analysis. So, you withdraw the blood from the patient and not have to go to a lab and simply do the analysis right there and then. Very useful for, you know, cases where you really need a fast analysis done right there and then. The other aspect of this is that it really allows you to do very efficient, very high through put analysis of large numbers of samples. So it's not just useful for clinicians in that case, but also bio-scientists who are doing, let's say, a drug discovery where they need to look at a lot of cells at the same time.

FLATOW: Is there something you would like to do with it that you can't do yet? You need to wait to another breakthrough you have to make out something.

Dr. YANG: Well, certainly I think one of the things we will be particularly interested in is to really drive down the resolution of the system even further. Because the resolution is actually given by the size of the holes that we use, we can actually punch the holes even smaller to the point that we can actually exceed the resolution of a conventional microscope. And that's actually gives you ability to see things that you may not otherwise see easily with a conventional microscope.

FLATOW: So if you're 10 or 20 times power now, what power would you like to go to?

Dr. YANG: Effectively, we want to go a resolution of maybe about 100 nanometers or 50 nanometers. So, that's really not equivalent in a conventional microscope for that.

FLATOW: Wow, well, good luck to you.

Dr. YANG: Oh, thank you, Ira.

FLATOW: And make sure you come back and talk about it when you - in your next step.

Dr. YANG: Sure. Thank you.

FLATOW: Changhuei Yang is assistant professor of Bioengineering and Electrical Engineering at Caltech in Pasadena. That's about it for this hour.

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