Abstract
The long-term goal of this project is to develop a compact, label-free, low-cost optical device for imaging epithelial
tissues in cancer detection and diagnosis. 80-90% cancers arise as carcinomas in epithelial tissues. Various
high resolution optical imaging techniques and devices have been developed for early detection and diagnosis
of epithelial diseases, but most of them are complicated and expensive, not suitable for point-of-care applications
and low resource setting environment.
We propose to develop a structured chromatic light sheet microscope. The key innovation is the use of a white
µLED array to generate structured chromatic light sheet, eliminating the need of external bulky light source and
scanner or spatial light modulator to obtain 3D tissue image. Another key innovation is the method of chromatic
slit confocal detection using a linear variable filter to block the out-of-the-light-sheet light to improve image
contrast and resolution. The image resolution and contrast will be further improved by taking and processing
three images modulated with phase-shifted structured light. It is also expected that the image resolution and
contrast in deeper layers can be improved by focusing and imaging a long wavelength light sheet deeper into
the tissue. In addition, volumetric image can be obtained by projecting structured light sheets sequentially
through the focal plane with 2D µLED array.
In this project, we will first develop a structured chromatic light sheet microscope (Aim 1), and then evaluate the
performance of the prototyped structured chromatic light sheet microscope in imaging epithelial tissue (Aim 2).
With the knowledge gained in Aims 1 and 2, we will also develop and evaluate a handheld structured chromatic
light sheet microscope for epithelial tissue imaging (Aim 3).
The concepts of chromatic light sheet and chromatic slit confocal detection will have profound impact on light
scattering imaging and potential applications in detection and diagnosis of epithelial cancers. This project will
result in an effective clinical tool for early detection of skin and oral cancers, which will significantly reduce
disease progression and mortality and improve quality of life. Further, this affordable tool will be very practical
for low-resource settings to reduce the burden of skin and oral cancers in low- and middle- income countries
(LMICs). In addition, the proposed microscope could enable improved localization of biopsy sites and delineation
of surgical margins, which will reduce the need for repeat and random biopsies.