Integrated, miniaturized fluorescence microscopes for biology research and general science education

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ABSTRACTTECHNICAL DESCRIPTION: This proposal concerns the development of a new type offluorescence microscope intended to make high-performance optical imaging vastly more accessible to science researchers and students. Traditionally, high-performance light microscopy requires exquisitely engineered objective lenses, whose complexity and expense limit availability. Even in the best research labs it is not common to find more than a handful of high-performance microscopes and objective lenses. In high schools and community colleges it is truly rare to find fine quality microscopes in teaching labs. Microscopes' bench-top size also precludes many potential uses, such as those inside other instrumentation or requiring portability.However, the technological seeds of a paradigm shift in light microscopy have recently been sown, due to the rise of mass-producible miniature lenses and opto-electronic components made for other purposes, such as in cell phone cameras. Light-emitting diodes (LED) and complementary metal-oxide semiconductor (CMOS) image sensors now provide quality light sources and high-resolution cameras available for a few dollars apiece. Thus, our work's basic premise is available technology enables high-performance microscopy while integrating all optical components - light source, lenses, filters, and camera - into one package about the sizeof a dime and costing far less than microscopes do today. To pursue this goal, this research will be an intimate collaboration between two Stanford labs of complementary expertise who have worked closely together for 2 years. Biophysicist Mark Schnitzer is deeply experienced in the design, construction, and use of fluorescence microscopes for in vivo brain imaging. Engineer Abbas El Gamal is one of the founders of theCMOS camera industry and a pioneer in digital imaging. To prove microscopy could ultimately become vastly more accessible, the two groups will design, build, test, and refine 20 integrated, miniature fluorescence microscopes with a design that could in principle be mass-fabricated. BROADER SIGNIFICANCE AND IMPORTANCE: The biological studies will focus on the Schnitzer lab's interests in motor neurobiology, but the work is poised to broadly impact research and education by helping to transform light microscopy from a relatively scarce resource into more of a commodity. As with any disruptive technology, the best applications might not emerge until after the affected communities re-think current technological roles.However, key future usages of these microscopes--or devices like them--may include: (1) Large-scale genetic or chemical screens of model organisms; (2) Time-lapse imaging of biological samples inside other instrumentation, such as incubators; (3) Imaging cellular functions of the human body; (4) In the field monitoring of ecological samples; (5) Cellular diagnostics in remote locations, underdeveloped nations, or the home; (6) Pathogen surveillance, such as in soil, agricultural products, air or water; (7) Giving each student a microscope for use in and outside the classroom. Although any mass production to address these diverse usages clearly remains a long way in the future, this project will more quickly impact education in the local community, via a partnership with a nearby university that offers secondary and associate's degree education to an historically underserved population. This will provide valuable feedback on the usability of our devices in the high school classroom. Another subset of the devices will be used in Stanford's teaching labs and will also permit multiple biology research labs to try the microscopes in their own projects.