Mobile health is changing health care delivery worldwide. Now, emerging cellphone-based diagnostic tests are altering the future for how laboratory testing will be conducted, particularly in remote areas. Cellphones are proving capable of imaging, sensing, processing, and communicating health-related data nearly instantaneously in field settings. It is estimated that there are more than 5 billion cellphone users globally and that 80 percent of the world’s population lives within range of a cellphone tower. In many underserved areas the wireless telecommunications infrastructure exceeds the reach of the health care infrastructure. This wireless infrastructure combined with cameras and digital components embedded in smartphones and cloud-based computing marks a powerful new front to fight global disease and helps bridge the gaps in access to health care. Applications for the cellphone-based diagnostic technology are near limitless with validation efforts already progressing for technologies using smartphones for digital microscopy and enabling rapid, qualitative immunoassay screening for infectious diseases, water quality, and food safety even in resource-limited settings. Experts say that products linking in vitro diagnostics products to cellular technology may be a crucial component in how the clinical diagnostics industry penetrates emerging markets in developing nations and will further propel the migration of clinical lab testing away from a central laboratory. Early evidence indicates that governmental agencies and nongovernmental organizations are both interested in these new, handheld technologies. Additionally tying the point-of-care test results into cloud-based monitoring can aid public health workers in identifying and managing disease outbreaks. “An aspect of public health when working in these areas is to take advantage of the resources you do have,” explains Gaetano Borriello, Ph.D., the Jerre D. Noe professor of computer science and engineering at the University of Washington. “In Tanzania there is one physician for 50,000 people. In Seattle there is one for 300 people. That is like all of Seattle having only 20 doctors. By applying technology you can leverage more limited human resources and can create more consistent, controllable standards of care and you can magnify the capabilities of health care workers.” Unlike in laboratories located in resource-rich settings, microscopes and cytometers may be unavailable in remote areas in developing countries, as are the skilled technicians necessary to run the tests and interpret results. Diagnoses in these underserved areas are further hampered by the frequent inability of patients to make long journeys, often by foot, to return to clinics to obtain test results and medications, if necessary. The advent of rapid diagnostic testing using lateral flow technology has made disease screening quicker and simpler allowing for testing in decentralized and often more convenient locations. Rapid diagnostic tests are commercially available for a wide variety of infectious diseases including HIV, malaria, tuberculosis, and syphilis. “Conventional rapid diagnostic tests are currently read manually, by eye, which is prone to error, especially if various different types of tests are being used by the health care worker,” said Aydogan Ozcan, Ph.D., a professor of electrical engineering and bioengineering at University of California, Los Angeles, whose lab has developed and is working toward commercialization of both microscopes and rapid diagnostic testing readers that clip onto cellphones. How It Works
Ozcan has developed a universal digital reader for all rapid diagnostic tests, which eliminates the need for manual decisionmaking and test interpretation. The reader, which weighs about 65 grams, clips onto a cellphone and includes an inexpensive lens, three LED arrays, and two AAA batteries. Improving upon some existing digital test readers, which are limited to test strips from a particular manufacturer, this platform is manufacturer-agnostic and can read nearly every type of rapid diagnostic test. A strip is inserted and converted into a digital image (within less than 0.2 seconds per image) using the cellphone’s existing camera unit and an app. The platform then rapidly reads the digitized test image to determine both if the test is valid and whether the result is positive or negative. Ozcan says the automation eliminates the potential for human errors, especially if the technician is administering multiple test types. The platform wirelessly transmits the test results to a global server, which processes them, stores them, and, using Google Maps, creates a map charting the spread of diseases both geographically and over time. Additionally, since the color changes in test strips don’t last more than a few hours in the field, the ability to store the digitized image indefinitely provides an added benefit. Ozcan says the platform has been tested using malaria, tuberculosis, and HIV both on Android-based smartphones and an iPhone. There are currently two strategies being employed in the development of cellphone-based diagnostics platforms. The first, as is the case with Ozcan’s technology, employs an attachment that will require U.S. Food and Drug Administration (FDA) approval as a medical device. Another strategy utilizes the cellphone’s technology strictly to transfer digital information to a cloud-based platform, where the processing and analysis occurs. While the FDA has yet to release definitive guidelines for approval of mobile-based diagnostics, Mobile Assay (Boulder, Colo.) is betting this approach will be quicker to be cleared through the FDA with validation required only for the server and software component, rather than cellphone add-on components. “If you make the phone anything but a conduit of information by using an add-on product, then all of a sudden there will be a whole lot more validation required,” says Warren Mauter, chief commercialization officer for Mobile Assay. “If you define a mobile product as a transporter of information and everything happens on a validated server and validated software, it will likely be a more straightforward process. Otherwise, what phone, what [operating system] version, each variable has to be addressed.” Additionally, Mauter believes that eliminating add-on units also broadens the potential market as analysis can be conducted with any phone with a camera. Mobile Assay’s technology employs similar components—cellphones, commercially available test strips, geographical tagging, and cloud computing. However, its system relies upon Mobile Image Ratiometry (MIR; developed by University of Colorado associate professor Don Cooper, Ph.D., chief science officer of Mobile Assay). MIR is a novel software algorithm that analyzes images and can precisely quantify the level of infection from test strips that previously only afforded qualitative analysis. Mobile Assay recently won a $100,000 Grand Challenges Exploration grant awarded by the Bill & Melinda Gates Foundation to fund a project titled “Lab on Mobile Device Platform for Seed Testing.” The company will initially target the fungus Botrytis—which can devastate crops like yams, potatoes, wheat, soybeans, onions, and sorghum around the world—and aflotoxins produced by Aspergillis fungi, which can contaminate seeds during storage and are among the most carcinogenic substances known. Cooper said the company’s MIR imaging technology can increase the sensitivity of test strips for Botrytis and aflotoxins by a factor of 100. Mauter says Mobile Assay is using a business model that relies on partnering with strategic partners with existing manufacturing or distribution channels to offer a premium service allowing for real-time quantification for commercial and clinical uses including applying the technology to quality control tracking at dairy farms. In addition to agricultural and global health applications, a number of health tests ranging from high cholesterol to abnormal thyroid-stimulating hormone levels could be conducted at home using specific test strips, with the data made available immediately to their health care providers over the Internet, Cooper suggests. Toward Commercialization
“The diagnostics market in the United States is much better understood. We know better what to expect, like a black box with input and output,” Ozcan tells DTTR
. “The diagnostics market for global health is less well understood . . . and harder to make a profit. [We want to] first enter the developed world with a disruptive innovation and take market share, then we can take more risk, recycling the technology and some of the know-how.” Commercialization of these technologies is in the earliest of stages. Some of these companies spun off from university research have been successful in raising funds necessary for validation studies. Here is a sampling of some of the companies working on cellphone-based diagnostic products:
- Holomic (Los Angeles), an optics company that was established to commercialize Ozcan’s technologies, is working on bringing to market a portfolio of microscopes and rapid diagnostic test readers. The company raised $2.5 million in seed funding from a strategic investor as well as $383,000 from a National Institutes of Health Small Business Innovation Research (SBIR) grant. The first product that will reach the market (expected in early 2013, Ozcan says) is based on LUCAS technology (Lensfree Ultra Wide-Field Cell Monitoring Array Platform based on Shadow Imaging). The lens-free, holographic microscope can attach to a camera unit of a cellphone. Slide samples are illuminated by a simple light-emitting diode (LED). This light is then scattered from biological sample, creating a hologram that can be used to mathematically reconstruct the microscopic image of the object on the detector array of the cellphone without the use of lenses. These holographic signatures are rapidly digitally processed and can be used to image blood cells, waterborne parasites (Giardia lamblia), or infectious agents (E. coli).
- Lifelens, a joint venture of researchers from several universities, including Wilson To, a Ph.D. student at University of California, Davis, at the time of the project’s inception, has developed a cellphone-based malaria diagnostic tool. The team has received funding from Microsoft Corp. as well as a $75,000 Microsoft Imagine Cup grant. The diagnostic system runs on a Windows Phone 7 operating system and uses a special lens attachment (350x zoom) to take a picture of a standard stained blood smear and runs an automated computer vision analysis to find any parasites present in the blood and determine the density (and progression) of the infection. Results take about two minutes. The geolocation-stamped information can then be uploaded into a network cloud to provide real-time worldwide data about malaria outbreaks. The group is looking to improve upon the power and cost of the $50 lens and says they are currently testing lenses of different materials that have magnification capabilities of 100x to 600x. The Lifelens team says the system has a 94 percent accuracy and a false positive rate of 10 percent to 15 percent, although results have not yet been published. Clinical trials are expected to begin by the end of summer 2013.
- CellScope (Berkeley, Calif.) spun out of research developed by Daniel Fletcher, Ph.D., a professor at the University of California Berkley, is based on technology that allows the camera of a standard cellphone to be turned into a diagnostic-quality microscope with a magnification of 5x to 60x, enabling the visualization of samples including blood smears and urine samples, followed by capture, organization, and transmission of images. The company envisions that most routine microscopy can be done on CellScope, including applications for malaria, sickle cell, and tuberculosis in global health as well as application of the platform for remote ear, throat, and skin exams in the United States. The startup received funding through Rock Health in 2011, a $1 million seed fund investment from Khosla Ventures to bring to market its otoscope smartphone attachment for remote diagnosis of ear infections. The patent-pending optical attachment is currently being tested by physicians in the Bay area.