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Medical Sciences Blog – Microscopy

Recently, I had the opportunity to attend an international microscopy conference which brought together an interdisciplinary and diverse group of scientists to share their research and assess the progress of the field. So I thought I’d share the experience in this latest medical sciences blog.

Presentations spanned advances in microscope technology to its application in answering biological questions, demonstrating the incredible versatility of these instruments. While microscopy most commonly brings to mind the simple light microscopes used to observe cell division of onion root tips in general biology class, scientists are continuously innovating optical, electron, and scanning probe techniques to visualize objects that cannot be seen with the naked eye. In fact, it was just last year that the Nobel Prize for chemistry was awarded to Eric Betzig, Stefan Hell, and William Moerner for the development of super-resolution microscopy, a technique which makes use of information from fluorescence to resolve cellular structures that are smaller than a wavelength of light, even in live cells. The technique of electron cryomycroscopy focuses a beam of accelerated electrons onto a specimen kept at cryogenic temperatures (often using liquid nitrogen or liquid helium) to construct models of biomolecules with near-atomic resolution. Despite the incredible images generated using these advanced microscopy techniques, it was a much simpler microscope which caught my eye at this conference.

The Foldscope, a foldable microscope manufactured for under $1, was developed by scientists at Stanford University as a tool to democratize science and revolutionize global health. This microscope is assembled from a single piece of paper using the principles of origami, with color coded instructions to transcend language barriers. That’s right, a single sheet of letter-sized paper contains all three stages that comprise a working microscope: an optical stage, with micro-optics embedded in the paper itself, an illumination stage, and a mask holding stage. Foldscope components are designed with utmost precision and configured for optical alignment so that small movements of the stages allow you to focus the microscope in micron steps. However, the simplicity and compactness of the design make it easy to use, durable, and field friendly. The Foldscope is crafted of waterproof paper, can easily fit into a pocket when assembled, and can withstand considerable force: promotional videos show Foldscopes to be functional after being stepped on by a person or even dropped from the third story of a building.

The basic design of a Foldscope is reminiscent of the much bulkier microscopes we are accustomed to, but can be tailored to suit a variety of applications such as fluorescence, brightfield, reflected light, polarization, and projection microscopy. This versatility allows each Foldscope to be configured for the particular stain used to identify a single pathogen in order to quickly diagnose disease: a bright field microscope is suitable for the Giemsa stain used to detect malaria-causing parasites, while the auramine-rhodamine stain used to visualize tuberculosis bacteria is visualized using a fluorescent microscope. This innovative approach to point of care diagnostics stands in stark contrast with previous global health initiatives which provide developing countries with bulky research microscopes that are not designed for field testing or for diagnostics. The Prakash lab is currently conducting clinical trials to demonstrate the efficacy of Foldscope for the point of care diagnosis of malaria, African sleeping sickness, Chagas disease, sickle cell disease, and many others.

In addition to serving as disease-specific diagnostic instruments for remote and resource poor settings, the Foldscope hopes to fulfill the mission that “every kid in the world should carry around a microscope.” While diagnostic Foldscopes are assembled prior to distribution, educational models are provided unfolded; this enables students to build the microscope themselves (a process which takes only 3-5 minutes), learning about the functional parts of a microscope in the process. This engagement in the assembly process encourages creativity in the use of the microscope, and even enables students to fix or modify it in the future. Access to these hands-on tools from a young age can not only empower students and promote scientific curiosity, but it could revolutionize global health by increasing understanding of germ theory: observing the microscopic organisms which cause disease could change perceptions of disease and, subsequently, of health.

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