Mobile Microscopy

00:00:11.13 Modern microscopes, like this one from Zeiss,
00:00:14.10 are remarkably powerful. But they're also rather large
00:00:18.11 and expensive. Wouldn't it be nice to have one that you could
00:00:21.26 take around with you? What I want to talk about today is
00:00:25.29 a project that is aimed at making microscopes more mobile.
00:00:29.09 Or taking advantage of things you already are carrying
00:00:32.12 with you to do microscopy. I'll set this up with a brief
00:00:36.05 history of microscopes, where they came from, how they
00:00:39.09 ended up like they are now. And then I'll talk a little bit about
00:00:42.04 why mobile microscopes might be useful and then I'll give you
00:00:45.16 an example of one that we've built to do microscopy
00:00:49.13 with a mobile phone. So looking back, the versions of
00:00:54.26 the Zeiss microscope before the one I showed you in the
00:00:57.16 last slide, these microscopes were works of art.
00:01:02.27 As you can tell from the pictures here, they were ornate,
00:01:06.26 they came in many different shapes and sizes, and these were all
00:01:11.05 parts of the Golub collection at UC Berkeley.
00:01:14.00 And they show how the design of microscopes has evolved
00:01:18.16 over many years. But you can tell right away that they are
00:01:22.01 much smaller, they had many fewer parts, and in some cases,
00:01:25.23 they were even made to be portable. One of the earliest
00:01:28.25 microscopes was the device developed by Antony van Leeuwenhoek.
00:01:32.12 And it was so simple that it had just a single lens. And that
00:01:37.02 small lens, right here at the top of the device, is mounted
00:01:42.18 on a metal plate, and the sample was positioned on that little
00:01:47.24 stick right there. And the screws at the bottom of the device
00:01:51.21 were used to position the sample in front of this little bulb lens.
00:01:55.17 And Antony van Leeuwenhoek was able to use this to
00:01:59.06 observe a wide range of different structures, and he was also
00:02:03.04 the first to identify microorganisms. And he called them
00:02:06.29 animalcules. Because, if you see them first, you can
00:02:09.22 call them whatever you want to call them.
00:02:11.26 So this is an example of a very powerful microscope.
00:02:14.25 He was able to see microorganisms and see them move.
00:02:18.00 And he was able to do that with a single lens system that
00:02:22.11 easily fit into his pocket. So why did things get so large?
00:02:26.18 Well, one of the reasons why they got so large is that there
00:02:30.05 are a wide range of different diseases that need studying.
00:02:33.13 And as we continue to study more diseases, imaging
00:02:37.19 is a critical part of many of the disease diagnosis processes.
00:02:44.09 But they also help us to learn about the life cycle to be able,
00:02:47.21 more recently, to label specific proteins and to observe
00:02:51.19 how therapies might be impacting the development of these
00:02:56.18 diseases. But imaging is something we still need to do.
00:03:00.22 And even though there are many different ways to do imaging,
00:03:03.06 many new contrasts, modalities, many improvements, and
00:03:07.00 cameras. Many diseases still need to be imaged, in order to
00:03:10.18 be diagnosed. Or at least imaging can be used for diagnosis.
00:03:14.02 So here are some bloodborne pathogens that if you take a
00:03:16.27 blood smear, and you look at it under a microscope, you can
00:03:19.18 confirm that in fact, you have this disease. Similarly,
00:03:23.25 with various gastrointestinal parasites, if you take a sample
00:03:28.11 and you're able to observe either the organism itself
00:03:32.11 or a cyst form of the organism, you can positively identify
00:03:36.19 that you have this disease. Now oftentimes, this isn't the fastest
00:03:40.13 way to do diagnosis in well-developed countries, but
00:03:44.22 in many parts of the world where these are more realistic
00:03:49.08 problems for the average person, microscopy is still a
00:03:52.15 central method for diagnosis. A good example of this is
00:03:56.17 tuberculosis. So tuberculosis continues to be a serious
00:03:59.23 problem, kills over 2 million people per year, and microscopes
00:04:04.06 are among the central most diagnostic tools available.
00:04:09.22 Even though there are a variety of alternate methods
00:04:13.09 that we would use in a developed hospital, in order to diagnose
00:04:18.09 the disease, microscopy is still very important in a number of
00:04:22.08 regions. And oftentimes, those are the regions without
00:04:25.02 access to high quality doctors, or high quality microscope
00:04:29.25 equipment that would be necessary. So as a way of emphasizing
00:04:33.12 that point, maybe I'll step off here for a moment.
00:04:36.12 This is a map that shows the distribution of tuberculosis
00:04:41.21 cases that were recorded across the globe. And you'll see
00:04:45.10 that the size of the countries are scaled for the incidence
00:04:49.27 rates of the disease. And so you'll notice that North America
00:04:53.15 and much of South America is virtually nonexistent, because we
00:04:57.06 don't have many cases. But Africa and Asia, and Southeast Asia
00:05:03.09 have significant caseloads. So let me contrast where
00:05:08.03 the cases are with where the doctors are. So now
00:05:12.14 all of a sudden, Africa is much, much smaller. Asia
00:05:16.16 as well, has reduced in scaling. But Africa -- but U.S.
00:05:22.06 North America and Europe are rather bloated. So we have
00:05:26.26 many doctors and with those doctors are well-equipped
00:05:30.19 hospitals. But the places where many of these infectious
00:05:34.26 diseases are, do not have the physicians capable or the
00:05:39.06 equipment available to do the diagnosis. So how can
00:05:42.07 mobile microscopy help? Well, it's become clear over the last
00:05:45.28 many years that mobile phones are becoming ubiquitous.
00:05:50.12 In countries across the globe, individuals have cell phones.
00:05:56.00 They're able to use them for a wide range of purposes.
00:05:59.05 And several years ago, a group of undergrads in microscopy
00:06:02.12 course that I taught, we began to experiment with using
00:06:06.05 the cameras that were emerging on phones to do
00:06:08.29 microscopic imaging, rather than taking -- using the phone to take
00:06:13.05 a picture of large things, like people or trees, could we use
00:06:17.10 that same camera without modifying the camera itself,
00:06:21.02 can we develop a lens system that will adapt that camera
00:06:25.04 for use to do microscopy? And our early efforts were encouraging
00:06:31.26 and we developed a simple device which we call CellScope, which
00:06:35.09 put together some eyepiece optics together with some objective
00:06:38.29 lens, and mounted it on the camera phone and allowed you
00:06:42.29 to take images. And to this device is something that we have been
00:06:47.10 developing over the last number of years, and the whole point
00:06:50.11 of this is to take advantage of the cell phones that many, many
00:06:55.01 consumers are already buying, which is pushing the price down
00:06:58.26 and increasing the performance. Can we harness that
00:07:02.00 technology and use it to do imaging? The overall concept
00:07:06.22 is that a person with the ability to take microscopic images
00:07:10.08 of relevant samples, such as a blood sample or a sputum
00:07:14.07 sample, they would be able to capture an image. Potentially
00:07:17.16 do some amount of image processing on that handset itself,
00:07:21.10 and then potentially send the image to a clinical expert who
00:07:26.02 could provide either a second opinion or improve the
00:07:30.25 advice about diagnosis and treatment. And so by using the
00:07:35.25 compact highly capable handset that are becoming ubiquitous
00:07:41.03 together with clinical experts who could be anywhere in the world,
00:07:45.18 they don't need to be in the region where the diseases are
00:07:47.21 found. A mobile microscope could help to enhance or
00:07:52.15 spread quality healthcare to places it hasn't reached yet.
00:07:56.17 So based on that original device, we've developed a
00:07:59.26 number of different devices. And I'll give a brief demonstration
00:08:03.18 of how we use these different technologies.
00:08:07.00 The goal of our project is to turn a standard cell phone
00:08:14.19 into a multipurpose microscope. So let me show you a few
00:08:17.09 examples. The original one we worked with was a system
00:08:24.02 that was high magnification, and the goal was to be able to look at
00:08:27.28 blood smears and resolve white blood cells, red blood cells,
00:08:31.01 and platelets. So what we've built is a system that has a little
00:08:36.01 light source, has a small stage for a slide, and then some optics
00:08:41.21 and mirrors that bring -- that come to a point here where
00:08:46.25 we want to line up with the camera of our cell phone. So we take this
00:08:49.29 cell phone and simply stick it in, and then we can move our
00:08:55.08 slide around simply by hand. And we can focus with a small
00:09:00.10 ring underneath the stage. And if we do that, then we can see
00:09:06.01 a magnified image. This is an image of some bacteria
00:09:10.00 and some blood, and one can pan around, adjust the exposure
00:09:15.20 or the focus, and take a photo, or even take a video
00:09:18.12 if this were a live sample and something were moving.
00:09:20.26 So that's all possible, again, no change to the phone.
00:09:24.17 It simply sticks into the holder. Now because the
00:09:28.29 phone itself is simply an imaging system, we might as well
00:09:32.14 use it to do different kinds of imaging. So another simple
00:09:36.29 clip on attachment that we've made for the same phone
00:09:40.08 is an otoscope, so an otoscope is used by primary care
00:09:45.05 physicians to inspect the ear. And so, this device has a simple
00:09:49.18 lens over the camera and is designed so that it captures
00:09:55.11 the same sort of image that a physician would see when looking
00:09:59.00 into the ear with a traditional otoscope. But in this case, you can
00:10:02.24 capture the image, you can email it, you can send it and you could
00:10:06.11 look at the ear at any hour of the day or night.
00:10:09.22 And a third device is focused not on ears, but on eyes.
00:10:15.17 This is a device that has been used to diagnose or screen
00:10:23.07 for trachoma. And this is done by holding the device up to
00:10:28.06 the patient's eye, flipping the eyelid, and inspecting the base of the
00:10:33.06 eyelashes. And this can be done, as well, with additional
00:10:39.00 lighting. So adding some illumination increases the ability
00:10:44.25 to resolve the details that are necessary. So again, small
00:10:48.17 improvements, small changes to the optics outside of the
00:10:54.16 phone are letting us do imaging with standard technology
00:10:59.18 at a range of different length scales.
00:11:02.11 With the ability to take microscopic images with your cell phone,
00:11:07.00 there are a range of different ways you could use such a
00:11:10.14 mobile microscope device. One that we've talked about already
00:11:13.19 is how healthcare, being able to take images of relevant
00:11:16.21 disease samples. But there are a number of other places where
00:11:19.24 mobile microscopy could be very useful. For example,
00:11:22.21 agriculture. What is causing that crop to die? What is
00:11:28.10 the cause of the disease. Taking a microscopic image of
00:11:32.14 leaf samples are one way to help diagnose the problem.
00:11:35.29 Similarly, a number of samples we might want to study
00:11:40.27 scientifically, are not things we can culture in a laboratory.
00:11:44.23 And so doing imaging in the field is necessary for those cases.
00:11:49.25 Having microscopes that are more portable, that are lower
00:11:53.29 cost, that are easier to deploy, may be a way of getting access,
00:11:59.04 getting imaging into places where imaging hasn't gotten
00:12:01.28 yet. And similarly, education. These devices we've enjoyed
00:12:06.25 working with and have had the chance to introduce to some
00:12:09.26 classrooms, some middle school classrooms. And that
00:12:13.21 experience has been enjoyable for both of us, and we're hopeful
00:12:16.17 that mobile microscopes can be useful not just for researchers
00:12:20.20 or healthcare providers, but also for teachers and students.
00:12:24.24 One example of where we've tried to take these devices
00:12:29.10 out into the field and learn about how they're useful is in
00:12:32.24 India. Together with World Health Partners, we evaluated whether
00:12:37.00 an ability to take simple blood smears in remote healthcare
00:12:43.10 clinics would be a useful capability for those regions.
00:12:48.00 And we're continuing efforts to understand where can microscopy
00:12:52.05 go. Where is it needed? What are the diseases and conditions
00:12:56.21 that it can be used to diagnose in the field?
00:12:59.08 And that's really the next stage of work. Now that we know
00:13:02.20 that microscopes can be built and they can be built
00:13:05.20 simply, cell phones can be used to power those microscopes
00:13:10.15 and provide the image collection capabilities, do they actually
00:13:13.28 work in the field? And that remains an open question.
00:13:16.18 And one we're very excited about.
00:13:18.27 So with that, I'll end and thank all of the people who have
00:13:21.23 contributed greatly to advancing this project and the support
00:13:26.00 we've received.

This Talk

Speaker: Daniel Fletcher

Audience:

Student
Researcher

Recorded: December 2010

Talk Overview

In this talk about mobile microscopy, Daniel Fletcher describes work from his lab to make small and inexpensive microscopes that can be project images to cameras on cellular phones. These mobile microscopes can be used for medical diagnostics in the field.

Questions

Mobile microscopes in this talk refer primarily to:
1. Microscopes that are used in teaching vans and brought to schools
2. Smaller versions of confocal microscopes
3. Compact magnifying optics that can be coupled to cell phone cameras
4. Confocal microscopes that can be disassembled and packed in suitcases
Which of the following diseases might be diagnosed with a mobile microscope
1. Diabetes
2. Tuberculosis
3. Influenza infection
4. Parkinson’s disease
Discussion Question: What new application might you think of for a miniature microscope?

Answers

Speaker Bio

Daniel Fletcher

Daniel Fletcher

Dan Fletcher is a Professor of Bioengineering at the University of California, Berkeley. His lab develops new instruments to study the cytoskeleton and its role in cell movement and shape change. Dr. Fletcher was a White House Fellow during the Bush to Obama transition. Continue Reading