An award is made to University of Connecticut to develop a cost-effective whole slide imaging (WSI) add-on kit. High-throughput whole slide imaging (WSI) system is an important tool for various biological research applications. By using WSI systems, large-scale biological samples can be digitalized with high resolution in seconds or minutes, significantly increasing laboratory efficiency and promoting the progress of science. This project aims to develop a $100 WSI add-on kit for high-throughput multimodal microscopy imaging. By adapting this add-on kit to an existing regular microscope platform, one can convert it into a high-throughput, multimodal WSI platform. The result from the WSI add-on kit is a comprehensive digital rending of the entire sample, on the order of centimeter in size, visible at diffraction-limited resolution, in two or three dimensions, and with multiple imaging modalities. Experiments that were typically carried out manually in single cell level and addressed a limited field of view at a time can now be done for the entire sample in an automated and intelligent manner. As high-content images are desired in many fields of biological and biomedical research, the dissemination of the WSI add-on kit in ~$100 budget could lead to new types of experimental designs in small research labs and benefit various health-related applications.
This project aims to develop the WSI add-on kit by integrating three different modules: 1) an autofocusing module that instantly identifies the optimal focal position of the sample, 2) a scanning module that drives the stages of a regular microscope in high speed, and 3) an illumination module that integrates multiple imaging modalities into the platform. For the autofocusing module, two pinhole-modulated cameras will be attached to the eyepiece ports for instant focal plane detection. By analyzing the captured images from these two eyepiece ports, one can infer the optimal focal position for a 2D thin section and the tomography structure of a 3D sample without a z-scan. Different z-sampling strategies can then be used for better image acquisition. For the scanning module, stepper motors and the associated gears will be used to control the motion of the microscope stages. Different mechanical coupling schemes will be tested and the best scheme will be chosen in terms of the scanning speed and positional repeatability. For the illumination module, a liquid crystal display will be inserted at the back-focal plane of the condenser lens. By setting different binary patterns on the display, this illumination module is able to integrate multiple imaging modalities into the platform, including brightfield, darkfield, phase contrast, quantitative phase, polarization, 3D tomography, and super-resolution Fourier ptychographic imaging. The education/outreach program of this project will include course development for graduate and undergraduate students at UConn, summer internships to high-school students and high-school/middle-school teachers. The knowledge generated through this project will be disseminated through conference presentations and workshops, publications in scientific journals, and news-room articles that raise the scientific literacy of the public. The protocol of building the WSI kit will be posted on a dedicated website. Industrial partners will be identified to promote the commercialization of the WSI add-on kit.