|Mobile Devices: On the Move from Laboratories to Clinics|
In May, SLAS Education Director Steve Hamilton, Ph.D. (aka The Lab Man), described in his blog a smartphone application that allows users to monitor their labs remotely and make system adjustments if needed. This advance, which is beginning to transform the way companies manage their compound screening and profiling systems, is but one way that mobile technology is changing the entire healthcare landscape, from drug discovery to patient care. Other advances promise to improve disease detection and diagnosis, as well as healthcare delivery, by turning familiar devices such as cell phones and video game consoles into platforms for data collection and point-of-care analysis.
A number of challenges must be met before many of these mobile devices are ready for prime time, according to experts interviewed for this article. But they also agree that—especially for laboratory science and technology professionals—the trend offers many opportunities for innovation.
Drug Discovery: “Cheaper, Faster”
Elaborating on the smartphone application that facilitates remote monitoring of a lab, Daniel G. Sipes, M.S., director of advanced automation technologies at the Genomics Institute of the Novartis Research Foundation (GNF), San Diego, CA, explains the benefits. “Before we deployed the application, systems operators had one option for monitoring the laboratory remotely—logging in from a home computer. Now, with their iPhones, they have full control of the instruments wherever they go. This allows them to start assays outside of normal business hours and respond immediately to any problems,” Sipes says.
“For example, if the operator is having dinner out and gets an alert that an assay performance has fallen off, he or she can log in, see what’s going on via a webcam, and respond by switching tips on a machine,” continues Sipes, a member of the SLAS Board of Directors and co-chair of SLAS2012. “Before the mobile system was introduced, we were alerted that something had gone wrong, but no one could respond unless they were at their home computer—or waited until the next day.
“Everyone just hit the ground running,” Sipes says. “The fact that you’re looking at a very small screen—as opposed to a PC monitor—takes some adjustment, but that’s really the only difference.” Overall, by reducing the number of repeat runs, the mobile device “saves reagents, speeds drug-discovery campaigns and allows us to use our systems more efficiently,” Sipes concludes. GNF was already running its systems 24/7 before going mobile. “But for companies who weren’t running systems around the clock, the device could mean a big jump in productivity, making campaigns cheaper and faster.”
Cell Phone Microscopy
At SLAS2012, electrical engineer and 2012 SLAS Innovation Award Finalist Aydogan Ozcan, Ph.D., professor of electrical and biomedical engineering at the University of California, Los Angeles, described a lensless imaging system that uses a cell phone as a platform for data processing and analysis. The system, called LUCAS (Lensless, Ultra-wide-field Cell monitoring Array platform based on Shadow imaging), earned the number-one spot in The Scientist magazine’s 2011 Top 10 Innovations contest. It essentially turns cell phones into holographic microscopes with the potential to revolutionize diagnosis and care, particularly in remote, resource-poor areas.
“Microscopy is a good starting point for mobile technology because it’s widely used for many things—telemedicine, environmental monitoring and materials science, among many others,” says Ozcan. “Regular microscopes are bulky, with lenses and other components that make them expensive and difficult to manage. Computational microscopes, by contrast, enable us to replace the lens and other analog components with digital algorithms, which vastly simplifies the device’s architecture.
“Instead of capturing the image of a cell or bacterium through a bunch of lenses, we illuminate cells with a light-emitting diode and capture the shadows they cast,” Ozcan continues. “It turns out that these shadows are quite rich. They’re different from our own shadows because at a micron scale, they are semi-transparent and can reveal internal cell features. Thus, each cell type casts a unique ‘textured’ shadow. Analysis of these shadows can identify the presence of disease cells, for example. All that’s needed is this inexpensive, lightweight (about 60 grams) device that is easy to use and generates diagnostic information almost immediately.
“The bottom line is that the cell phone is not just something we talk into. It is a platform that contains a lot of different components, technologies, hardware and software,” Ozcan explains. "It’s not that a cell phone is less complicated than a car or your laptop. It’s probably more complicated in many ways because it’s so much smaller. What makes it a cost effective device is that there are so many of them--approximately two billion manufactured every year. The sheer volume keeps overall costs down."
One of the first applications of the technology will be a cell phone-based rapid-diagnostic-test reader that Ozcan says should be available for distribution by the end of 2012. The device could potentially assist in the tracking of infectious diseases worldwide and in identifying emerging epidemics.
On another front, UCLA pediatric infectious diseases specialist Karin Nielsen, M.D., is helping to evaluate the accuracy of the images provided by LUCAS and the feasibility of deploying the technology in remote areas for point-of-care purposes. “One application we’re testing is the identification of intestinal parasites—in particular, giardia—in stools,” says Nielsen. “An earlier application of LUCAS could detect the presence of bacteria such as e-coli or cryptosporidium in a drop of water. Since diarrhea is a major problem affecting children in less-developed countries, we wanted to see whether LUCAS could accurately detect the parasite in a stool sample.”
Yet another project involves using LUCAS to do complete blood counts to help direct among AIDS patients in remote parts of Brazil.
Video Game Diagnostics
The cell phone is by no means the only platform that can be brought into play for clinical diagnostics and epidemiology. A recent TIME magazine headline asks, “At What Point Do We Stop Calling These Things ‘Game Consoles?’”. Focusing on entertainment, the article begins by exploring the versatility of Microsoft’s Xbox 360, a game console that also streams movies and TV shows, and will soon offer a music service, web browser and technology that will let it “talk to phones and tablets.” By the end of a presentation on the console at a recent video game event, the author wrote, “Xbox felt less like a game console and more like a Swiss Army Knife of living-room entertainment…like a PC…that happens to be tailored to amusement rather than productivity.”
That same versatility is becoming apparent on the productivity end as well. In 2011, researchers reported on the utility of a mobile health monitoring system using a hand-held Nintendo DS game console to help detect cardiac abnormalities based on transmitted electrocardiogram signals. More recently, the Ozcan Research Group created a video game for cell phones and PCs to see whether it could teach untrained observers to provide reliable malaria diagnoses based on digital images. They found that a small group of non-experts playing the game were collectively able to distinguish malaria-infected red blood cells from healthy red blood cells with an accuracy that was within 1.25 percent of the decisions made by a pathologist.
The team plans to take advantage of online crowd-sourcing to train large numbers of people, who they predict would get collectively better at analyzing such images. That kind of platform potentially could be used to combine decisions of minimally trained healthcare workers in underserved regions to boost the accuracy of their diagnoses.
“It’s a provocative idea, and would probably cause some controversy,” Nielsen acknowledges. “I imagine that many trained microscopists and microbiologists would say, ‘How could someone with no skills who plays a video game identify malaria as well as I can, with all my years of experience?’ So we must have clear evidence that it works in clinical trials before we attempt to implement it on a large scale.” The group plans to test the strategy at clinical sites in Brazil and sub-Saharan Africa.
Challenges and Opportunities
Ozcan is aware of the difficulties his team and others face in bringing cell phone diagnostics to those in need. “We have some big challenges,” he concedes. One is how to reliably assess and interpret the huge amount of data that will be pouring in, once the power of cell phones is harnessed for point-of-care purposes. As discussed in the SLAS ELN article on next-generation sequencing, not all data are created equal.
Says Ozcan, “If these diagnostic tests are deployed on a wide scale, we have more throughput, more megapixels, more information, more channel capacity, and we’re delivering more juice to our systems. Who’s going to sort this big data? Who’s going to say if it’s relevant or not relevant? Who’s going to classify it? Who’s going to make predictions based on it?”
Moore’s Law predicts exponential growth of technology every two years. The precept “holds true for cell phone microscopy, computational imaging, high-throughput screening, telemedicine and all related technologies,” he observes. But the number and knowledge base of technicians, healthcare workers and others who might be qualified to interpret the data are not keeping pace.
Those concerns and more are echoed in a recently released American Academy of Microbiology publication, Bringing the Lab to the Patient: Developing Point-of-Care Diagnostics for Resource-Limited Settings. The report grew out of a colloquium in which participants explored the challenges inherent in bringing mobile devices to market and to scale for healthcare purposes. In the announcement of the publication’s release, Colloquium Chair Keith Klugman is quoted as saying:
“POCTs [point-of-care tests] are developed by researchers and engineers and implemented by a separate group of public health professionals at a local level. There are so many variables that can make or break the effectiveness of any test, and so often the scientists and engineers developing the test are not aware of them. POCTs that perform well in testing may not function ‘on the ground’ in resource limited areas, where there may not be running water, electricity or trained personnel to administer the test.”
Challenges to implementation also exist in developed countries, according to Neven Karlovac, Ph.D., CEO of Holomic LLC. Holomic was founded by Karlovac, Ozcan and Gilbert Hakim, CEO and founder of SCC Soft Computer, to commercialize the technologies invented by the UCLA Ozcan Research Group.
“Despite the wonderful possibilities, there are many complications with regard to quality control, data management, training of personnel, billing and liability that, in the aggregate, have definitely hampered the growth of point-of-care solutions,” Karlovac says. Specifically with regard to cell phone applications, “patient data security and patient privacy are significant issues that also need to be addressed.”
“Safety is another hurdle,” says Jonathan Collins, principal analyst, mHealth & M2M, for ABI Research. ABI recently released a report, Mobile Devices and mHealth that examines the market potential of mobile healthcare devices—mainly for consumer self-monitoring—for the next five years. “If you're moving a mobile phone into the medical domain, you’re going into an area where there's always been, and rightly so, strong regulation to ensure that devices provide accurate readings,” he says.
“Other issues and gray areas surround not only the secure transmission of data, but how a regulatory body certifies a medical device that changes every six or eight months,” Collins continues. “Would a mobile phone vendor be required to have the entire platform recertified, or just the operating system or application upgrade? The field is moving from dedicated, managed devices with long life spans to devices that might not be dedicated to a single application, and that are capable of doing a range of things, based on a very broad platform that can't go through a full certification process for each model upgrade.” Furthermore, stakeholders need to be clear about who owns the data that is transmitted and/or processed by the device—the network operator, the medical institution or the patient?
In the United States, the Food and Drug Administration has provided what Collins says is a “clear signal” to application developers about how it intends to control mobile handset use in healthcare. In February 2011, the agency cleared for marketing two such applications—one is an ultrasound mobile application delivered on a smartphone purchased by healthcare professionals specifically for that purpose. The other is an ultrasound application that allows clinicians to examine and assess ultrasound images on any iPhone handset (the software company subsequently received clearance for an updated version that adds X-ray and radiation oncology capabilities.
In July 2011, the FDA released a draft guidance on mobile medical applications that outlines some of the key requirements for these applications, and how they would be regulated. The guidance covers 1) mobile apps that are an extension of medical devices that connect to control display, store, analyze or transmit patient-specific medical device data; 2) mobile apps that transform the handset into a medical device by using attachments, display screens or sensors or by including functionalities similar to those of currently regulated medical devices; and 3) mobile apps that allow the user to use patient-specific information and output a patient-specific result, diagnosis or treatment recommendation to be used in clinical practice or to assist in making clinical decisions.
“The reports we hear are that the FDA is not against these devices and is working hard with industry to move things forward and make the requirements as simple and clear as possible,” Collins comments.
Whether they’re being deployed in a research lab for drug discovery or in the field to help save lives, it’s clear that the use of mobile devices and other innovative technologies will continue to grow. “This doesn’t portend the end, overnight, of the lab as we know it,” says SLAS Education Director Hamilton. “However, we clearly are in an evolution, and it behooves SLAS members to stay informed and be ready to adapt—and to explore the possibilities.”
SLAS Can Help
SLAS2013 will address further the topics explored in this feature. Ozcan is chairing a session titled “On-chip Imaging” as part of the Micro/Nano Technologies track. Additionally, SLAS2013 Co-chairs Aaron Wheeler, Ph.D., from Toronto University and Jonathan O’Connell, Ph.D., from Bristol-Myers Squibb Company point to the High-Throughput Technologies track sessions “Cutting Edge Technology Developments” and “New Developments and Applications in High-Throughput Screening Technologies and Automation” as including talks that may address emerging mobile technologies. They also expect that submitted podium abstracts may result in additional matches, especially in the area of iPhone-driven analysis systems. Watch the SLAS2013 website for final session descriptions later this summer; abstracts are being accepted through July 30.
Ozcan has recently published two JALA articles. “Lens-Free Imaging for Biological Applications” is in the February 2012 issue. He also collaborated with Dino Di Carlo’s group at the University of California on “A Mechanical Biomarker of Cell State in Medicine.” This manuscript was also in the February 2012 issue.