Journal Publication:
Gordon, P., Venancio, V. P., Mertens-Talcott, S. U., & Coté, G. (2019). Portable bright-field, fluorescence, and cross-polarized microscope toward point-of-care imaging diagnostics. Journal of Biomedical Optics, 24(9), 096502.
Few tools are as ubiquitously useful for medical diagnosis as the benchtop microscope, making the lack of microscopy services in many remote areas a significant restriction on the quality of care. In this proposal the focus will be on the research and development of a portable, digital, multimodal microscope to be used in place of the benchtop microscope for disease diagnosis in remote areas by leveraging the ever-improving quality and affordability of new sensors and optical components. If successful, it may enable the diagnosis of conditions such as malaria, tuberculosis, sickle-cell anemia, and more in remote regions around the world.
Malaria, specifically, has been one of the most lethal diseases that modern humankind has ever known. Malaria results from a blood-borne infection with one of several species of Plasmodium parasites, causing 445,000 death annually; it is still a major health concern in some parts of the world today. Although overall global incidence rates have declined over the past several decades, they have been slowly increasing since reaching a minimum/low point of 210 million cases annually in 2014. Reducing disease incidence and mortality in the most remote and disease-endemic regions remains a difficult challenge, but recent data suggest that progress may be made in reducing malaria mortality by improving access to care, especially among children in sub-Saharan Africa, one of the most vulnerable global populations. According to the 2017 World Malaria Report, only a median of 47% of febrile children were taken for examination by trained medical providers, and surveys also indicate that a median 39% of these children did not receive any medical attention, possibly due to poor access to health-care services or lack of awareness in those giving care [9]. In malaria endemic areas, fevers are often self-medicated without any disease confirmation, with reported over-diagnosis rates as high as 83%, leading to wasted resources, increased risk of developing drug-resistance, and ignorance of other febrile maladies.
After over 100 years of use, brightfield microscopy of Giemsa-stained blood films is still the recommended best clinical practice for lab-based malaria diagnosis. The test requires a dedicated and well-maintained central laboratory with trained microscopists who can perform the skilled labor necessary to prepare and evaluate the test with a high degree of accuracy. Blood drawn from a patient is placed onto a glass microscope slide where it is formed into both thick and thin films, which are examined using 1,000x magnification benchtop microscopy under brightfield illumination . Implementing a similar diagnostic method that relies upon direct observation of parasite morphology is difficult in a point-of-care device because of the high-precision optics required to achieve the necessary resolution.
If laboratory microscopy is unavailable, lateral-flow based RDT’s use a drop of a patient’s blood to confirm the presence and limited speciation of Plasmodia parasites by detecting the presence of parasite-specific proteins. However, the RDT’s do not provide quantifiable information about the severity of infection, meaning that patients on the cusp of a severe infection may not receive the intensive treatment they need. Additionally, RDT misdiagnoses can result from latent, non-clinical parasitemia or from mutated parasites that omit the target analyte. Several other methods have been proposed to diagnose malaria by detecting the parasitic byproduct hemozoin, which has unique birefringence, absorption, magnetic, chemical, acoustic, and thermal properties. However, hemozoin only begins to develop in later stages of infections, meaning that it is unreliable for early stage disease diagnosis. The hemozoin crystals can also reside in the bloodstream after an infection has been cured, making them unreliable when used as the only diagnostic biomarker.
Paul Gordon 