Your Smart Phone as Medical Lab InstrumentLarry Maloney | December 30, 2014
High-priced microscopes, spectrometers and chromatography devices get all the attention in lab equipment circles, but an electrical engineering professor and his team at the University of California Los Angeles (UCLA) have devised ways to turn the everyday cell phone into inexpensive yet useful diagnostic and scientific instruments.
With 27 issued and licensed patents, Aydogan Ozcan has married optics, computing power, software and mobile phones to create low-cost devices that detect viruses and bacteria, analyze cell behavior and examine tissue samples. Dr. Ozcan described the technologies behind these innovative instruments in an interview with Engineering360 contributing editor Larry Maloney.
Maloney: What is the special niche of your team’s cell phone-based instruments?
Ozcan: We use the cell phone or smart phone, as well as other consumer electronic devices, to create new measurement tools, many of them for medical diagnostics, imaging and sensing applications. These compact, lightweight devices are designed to replace more bulky and expensive conventional instruments.
Maloney: What are the underlying technologies behind your seminal device, a lens-free microscope?
Ozcan: If you were to start from scratch today to invent the microscope, how would it look? That’s where the cell phone comes into the picture. First of all, the optical components of a cell phone are very advanced. The same Moore’s Law that applies to rapid advances in transistor count and computing power also applies to megapixel counts in cell phone cameras. These counts have been doubling every two years, rising to more than 40 megapixels today.
The next key element behind our design is computation. Light microscopes were invented a long time ago when there were no computers. By contrast, the cell phone is like a miniature supercomputer, with powerful graphics processing units. That means that you can capture high-end microscopic images, as well as process these measurements and the resulting data.
The third element that makes the mobile phone such a special platform is its connectivity, with 7 billion subscribers around the world. So you can capture images of specimen at the micro- and nanoscale level, and share them and the resulting analysis remotely as needed. About 75% of these phones are in developing countries where diagnostic labs are scarce.
Maloney: How do these building blocks come together in your device?
Ozcan: Let’s start with the lens-free cell phone microscope, although more than a dozen different devices and measurement tools have grown up around our basic technology. This microscope, which attaches to the cell phone’s camera, features a powerful CMOS (complementary metal–oxide–semiconductor) imaging chip with typically 5-10 million photodetectors that can sample the intensity of light and capture an image that impinges on the chip. In an application, you load a cell or tissue sample onto the chip and slide it into the side of the microscope. There’s a sub-millimeter gap between the specimen and the chip and an LED light source creates shadows of the sample onto the chip.
In our system, we treat these shadows as holograms and use algorithms to reverse the optical diffraction and create an actual image of the specimen. Users can then transmit these images to diagnostic labs or other facilities. Not only is this design compact, lightweight and powerful, but the field of view is significantly larger than that of conventional light microscopes. So we can look at very large volumes on a specimen, which gives us the throughput for studying samples in new ways.
Maloney: Can you cite some examples of applications for this technology?
Ozcan: Early applications of the microscope included detection of viruses and bacteria, blood count and imaging of pathogenic microorganisms in water.
In general, this platform can image and study any sample that is about 40 nm in diameter or larger. A typical virus measures about 50 to 200 nm. More recent examples include the ability to track the movement of sperms in three dimensions at extreme throughputs, unattainable by any other technology. Veterinarians and animal breeders could use these compact microscopes, weighing less than 100 grams, to assess sperm quality in the field, rather than sending specimens to a laboratory. This technology could also benefit in-vitro fertilization practices, as well as research on sperm behavior and the effect of chemicals or drugs on sperm quality.
Lens-free microscopy can also deliver high-quality, 3D images of tissues, such as those that pathologists typically study under traditional light microscopes. Through blind tests, we validated that a board-certified pathologist can achieve 99% accuracy in identifying breast cancer tissue using our microscopic images of tissue slices. Imagine the value of these devices in the early diagnosis of cancer, especially in resource-poor countries where there are very few pathologists and other specialists. Using these highly portable microscopes, a nurse can capture the image of a tissue specimen and transmit it to a diagnostic center for expert assessment.
Maloney: What are some of the other devices that your research group has developed as offshoots of this technology?
Ozcan: One example is a compact flow cytometer that attaches to a mobile phone. This device can capture and analyze microscopic videos of flowing blood cells, bacteria and other liquid specimens. We’ve also developed various attachments to our basic platform that turn the mobile phone into a blood analyzer, as well as portable detectors for E.coli, water-borne Giardia particles, heavy metals and even peanut allergens. In the case of harmful heavy metals in drinking water, our device can detect mercury concentrations down to 3-4 parts per billion level of sensitivity. This particular attachment weighs less than 40 grams, and the cost per test is just a few cents.
Maloney: What progress have you made in commercializing these devices?
Ozcan: In 2011, I founded Holomic, a Los Angeles company that focuses on mobile diagnostics technology. introduced in 2012 and a fluorescent immunoassay reader that debuted in 2014. Holomic is targeting developed countries, as well as underdeveloped countries in Africa, Asia and the Middle East. Even in the U.S., there are many underserved areas where mobile diagnostics could make a significant impact.
Maloney: Beyond the mobile phone, your team is also working with the wearable Google Glass device as another potential platform for diagnostics. What do you see as its potential?
Ozcan: We use the Google Glass camera to capture images of biomedical specimens on test strips that carry QR codes (quick response or matrix barcode) for identification and embedded patient information. Without relying on any additional devices, Glass users can upload these images to our server platform for analysis. The advantage of Google Glass versus the mobile phone is its unique hands-free, voice-activated user interface. That’s important because in some tests, such as dangerous, cross-contamination situations, you don’t want the specimen to touch your device. The disadvantage of Google Glass is that it functions in ambient light conditions.
In contrast, our mobile phone attachments feature an enclosed light source, which enables more sensitive measurements and operation in all kinds of environments day and night. Even so, we’ve had good success with Google Glass in detecting the presence of such conditions as HIV, malaria and prostate cancer (prostate specific antigen or PSA). We are already licensing the software for this application through Holomic.
Maloney: Do you envision using other consumer electronic devices as diagnostic platforms?
Ozcan: Certainly, there are other devices that show potential, such as flat-bed scanners. For example, we’ve created the world’s first fluorescent microscope on a flat-bed scanner. This device provides an ultra-large field of view, as large as A4-size paper (about 532 cm2), so scanners hold promise for very large samples.
But my group is still very much focused on pushing the limits of devices and attachments tied to computational imaging and sensing. It is very exciting work and the results are getting better and better every day.
For example, when we started this work seven or eight years ago, our microscopes could barely image a red blood cell, which measures about 7-8 microns. Now, we can image sub 50-nm particles. That’s more than 150 times smaller than a red blood cell. And very recently, we published results of our work showing the ability to image and size single-molecule DNA –-a 2-nm feature--on a mobile phone using fluorescent microscopy. How many science students have ever viewed a single-DNA molecule? These powerful but inexpensive devices could make that possible worldwide.