Microscopy and imaging systems are critical diagnostic tools for both infectious and chronic diseases and can improve health in low- to middle-income countries. Although diseases like malaria and tuberculosis can be treated successfully when detected early, the World Health Organization estimates that in 2008, 1.3 million people died from tuberculosis and nearly 1 million people died from malaria.1, 2, 3, 4
Most of these deaths occur in developing countries where high capital costs, complex maintenance requirements, and a lack of trained users limit access to research-grade microscopy, imaging systems, and other diagnostic services. Distance is also a factor. Some centralized health centers offering these services are too far away from the people who could use them, and this may cause patients to defer or delay medical treatment.5
Recent advances in fluorescence microscopy, such as LED microscopes, aim to meet some of these challenges. But high cost and lack of portability still prevent these tools from being widely used in the developing world.5
Researchers at Rice University and the Texas Medical Center (USA) are developing innovative tools in microscopy and imaging that are inexpensive, durable, and portable enough to be used in rural and community health centers with limited infrastructure in the developing world.
Microscopy to go
Andrew Miller, a 2009 Rice University bioengineering graduate, designed one such microscope while he was a student. Miller’s GlobalFocus microscope is a portable, battery-powered, inverted-fluorescence and bright-field microscope with up to 1,000x magnification. Fluorescence microscopy increases sensitivity in diagnosing malaria and tuberculosis and reduces the time and expertise required to interpret diagnostic results.5
The GlobalFocus microscope was designed by Andrew Miller when he was an undergraduate at Rice University. It can be manufactured for about $240. Photo courtesy of Andrew Miller
The cost, durability, ease of repair, and portability of the microscope make it appropriate for resource-poor settings in developing countries. The GlobalFocus is designed with over-the-counter components, using a flashlight for the light source, for example. It can be manufactured for about $240, compared to $40,000 for conventional microscopy with similar functions.5
By radically simplifying the design of the microscope and by leveraging low-cost, over-the-counter parts, we have designed the GlobalFocus to be a truly ‘out-of-lab’ friendly diagnostic microscope that can operate in bright-field or fluorescence mode and still cost less than $250 to manufacture, Miller says.
An inexpensive, single-body component provides mounting surfaces for the optical components, eliminating moving parts that could be damaged. The light source and mechanical stage can be removed and safely transported within a protective case. Additionally, the over-the-counter and standard-sized components may be replaced easily. The 3-pound microscope is compact enough to be transported or shipped easily to remote areas.5
TB and malaria detection
Despite these modifications, the microscope has sufficient resolution to discern malaria parasites in bright-field mode (See below) and tuberculosis bacilli in fluorescence mode. In a clinical study evaluating 63 direct, decontaminated, and serial dilution sputum smears from suspected TB patients, positive and negative results from the GlobalFocus microscope corresponded with results from a clinical-grade microscope 98.4% of the time.6
Top image is of malaria taken with the GlobalFocus microscope (100x/1.25 oil). The image of malaria at bottom was taken with a Zeiss (100x/1.3 oil). Photos courtesy of Andrew Miller
Future studies will test the reliability and ease-of-use of the GlobalFocus microscope. However, the present system is a convincing model for the design of a low-cost, portable, bright-field and fluorescence microscope to detect infectious diseases.5
Miller founded Oris Diagnostics and is on track to manufacture the GlobalFocus microscope in two years.6
Imaging systems to diagnose and manage cancer face similar financial and infrastructural barriers to dissemination in the developing world. Most cancer diagnoses in those settings are based purely on clinical signs and symptoms because the cost and complexity of maintaining diagnostic imaging facilities and pathology labs is prohibitive.
As with malaria and TB, providing access to objective screening tools at the point of care for cancer screening can have significant impact on mortality and reduce the burden on overworked pathology labs.
While healthcare providers have traditionally used optical tools such as endoscopes, colposcopes, and surgical microscopes in cancer management, new high-resolution optical imaging instruments, driven by advances in consumer electronics, are being developed to detect not only reflected white light, but additional signals arising from cancer biomarkers. These biomarkers are carried in the fluorescence, polarization, and narrowband reflectance of light.7
For example, researchers at Rice University and the University of Texas M.D. Anderson Cancer Center developed a high-resolution microendoscope, a portable, battery-powered digital imaging system to detect pre-cancer. After applying a fluorescent contrast agent to the tissue to be imaged, the distal end of a flexible fiber optic bundle (1 mm in diameter) is placed on the tissue. Fluorescent light emitted from the tissue returns through the same fiber and is imaged onto a high-sensitivity CCD camera.7
Clinical studies are being held on this high-resolution, portable microendoscope. Developed by Texas researchers, it weighs only 6 pounds and is powered by a battery. Photo courtesy of Mark Pierce
This system is contained in a portable package weighing six pounds. It connects to a laptop computer via Firewire ports to enable simultaneous imaging within a LabVIEW-based used interface. The image analysis can be automated so that community health workers can perform rapid screening without complex infrastructure.7
Clinical studies are under way to compare the performance of this device against large-scale counterparts.7
In addition to being cost effective and portable, the high-resolution microendoscope can provide an alternative to biopsy for evaluating cellular morphology when histo- and cytopathology facilities are not available.
Even in well-equipped facilities, optical imaging can guide the clinician to the most appropriate sites for tissue sampling, which may significantly reduce cost and increase the value of biopsies when they are required.7
Despite the advantages of these and other low-cost microscopy and imaging systems, several other conditions must be met before these tools can be broadly disseminated and adopted in the developing world.
First, better needs-assessment studies are required to delineate design requirements for technology to be used in developing countries. For example, microscopy and imaging technologies for the developing world may require affordable image contrast agents that can survive in environments with extreme temperatures and humidity levels.
Methods of quality control for devices in low-resource settings should ensure that instruments can remain calibrated and functional without trained technicians.
Finally, these technologies must be developed without the financial support that flows from traditional market incentives, which do not reward the development of technologies for low-resource settings.7
Andrew Miller and his prototype microscope.
1. WHO Fact Sheet
2. WHO Fact Sheet
3. H. Tunstall-Pedoe, Preventing Chronic Diseases. A vital investment: WHO Global Report, International Journal of Epidemiology 35(4), p. 1107 (2006).
4. L.A. Jones, J.A. Chilton, R. A. Hajek, N.K. Iammarino, L. Laufman, Between and within: international perspectives on cancer and health disparities, Journal of Clinical Oncology 24(14), pp. 2204-2208 (2006).
5. A. Miller, G. Davis, Z.M. Oden, and R. Richards-Kortum, Portable, battery-operated, fluorescence field microscope for the developing world (unpublished manuscript), Rice University Department of Bioengineering (2010).
6. A. Miller, Global Focus—Portable, battery-operated, fluorescence field microscope for the developing world, PowerPoint presentation at Unite for Sight conference, New Haven, CT (USA) (2010).
7. N. Bedard, M. Pierce, A. El-Nagger, S. Anandasabapathy, A. Gillenwater, R. Richards-Kortum, Emerging roles for multimodal optical imaging in early cancer detection: a global challenge, Technology in Cancer Research & Treatment 9(2), pp. 211-217 (2010).
Developing world shoulders burden of chronic disease
As globalization spurs economic development, the developing world is beginning to shoulder a greater burden of chronic disease.
Today, more than 70% of the world’s cancer deaths occur in developing countries where 80% of patients present with advanced diseases at the time of diagnosis.
Low-cost, portable microscopy and imaging systems that can detect and diagnose cancer have the potential to improve health outcomes in many regions of the world.
Sources: See references 1-4 above.
Smart technology for healthcare
Among other researchers who are developing lightweight and inexpensive devices for medical imaging and diagnostics is SPIE member Aydogan Ozcan. His group at UCLA has built a digital microscope that can plug into a cell phone.
The device costs just $3 and can perform basic medical diagnostics. It has no lenses but uses software, an LED, and a light sensor to extract information from the images.
Ozcan has also recently introduced a lens-free, on-chip design for optical cytometry that uses holographic images of blood cells. More: spie.org/lucas
By supporting early detection and diagnosis of disease, microscopy and imaging systems can improve the likelihood that treatment and disease management will be effective.
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Lauren Vestewig is executive director of Rice 360°: Institute for Global Health Technologies at Rice University in Houston (USA). This article was adapted from two manuscripts5,7 authored by Rice 360° founding director Rebecca Richards-Kortum and research colleagues. Rice 360° partners with communities throughout the world to design and implement low-cost, high-performance health technologies. More than 19,000 people in 15 countries have benefited from technologies designed by students and faculty in Rice 360°. More: www.rice360.rice.edu
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