As one of the smallest endoscopes that have been demonstrated, the spectrally encoded endoscope (SEE) shows potential
for the use in minimally invasive surgeries. While the original SEE is designed for side-view applications, the forwardview
(FV) scope is more desired by physicians for many clinical applications because it provides a more natural
navigation. Several FV SEEs have been designed in the past, which involve either multiple optical elements or one
optical element with multiple optically active surfaces. Here we report a complete FV SEE which comprises a rotating
illumination probe within a drive cable, a sheath and a window to cover the optics, a customized spectrometer, hardware
controllers for both motor control and synchronization, and a software suite to capture, process and store images and
videos. In this solution, the optical axis is straight and the dispersion element, i.e. the grating, is designed such that the
slightly focused light after the focusing element will be dispersed by the grating, covering forward view angles with high
diffraction efficiencies. As such, the illumination probe is fabricated with a diameter of only 275 μm. The twodimensional
video-rate image acquisition is realized by rotating the illumination optics at 30 Hz. In one finished design,
the scope diameter including the window assembly is 1.2 mm.
Optical films with microstructures can achieve uniform illuminance on the target and glare control with no registration to LEDs. An engineered optical film design with microstructures on both sides is demonstrated. A spacing ratio of 1.64 is obtained compared to 1.28 with just LEDs while there is less light at higher angles for better glare ratings.
The gold standard in histopathology relies on manual investigation of stained tissue biopsies. A sensitive and quantitative method for in situ tissue specimen inspection is highly desirable, as it would allow early disease diagnosis and automatic screening. Here we demonstrate that quantitative phase imaging of entire unstained biopsies has the potential to fulfill this requirement. Our data indicates that the refractive index distribution of histopathology slides, which contains information about the molecular scale organization of tissue, reveals prostate tumors and breast calcifications. These optical maps report on subtle, nanoscale morphological properties of tissues and cells that cannot be recovered by common stains, including hematoxylin and eosin. We found that cancer progression significantly alters the tissue organization, as exhibited by consistently higher refractive index variance in prostate tumors versus normal regions. Furthermore, using the quantitative phase information, we obtained the spatially resolved scattering mean free path and anisotropy factor g for entire biopsies and demonstrated their direct correlation with tumor presence. In essence, our results show that the tissue refractive index reports on the nanoscale tissue architecture and, in principle, can be used as an intrinsic marker for cancer diagnosis.
We show that applying the Laplace operator to a speckle-free quantitative phase image reveals an unprecedented level of detail in cell structure, without the gradient artifacts associated with differential interference contrast microscopy, or photobleaching and phototoxicity limitations common in fluorescence microscopy. This method, referred to as Laplace phase microscopy, is an efficient tool for tracking vesicles and organelles in living cells. The principle is demonstrated by tracking organelles in cardiomyocytes and vesicles in neurites of hippocampal neurons, which to our knowledge are the first label-free diffusion measurements of the organelles in such cells.
advent of automatic analyzers such as flow cytometers and impedance counters. Though these current methods have proven to be indispensible tools for physicians and researchers alike, they provide limited information on the detailed morphology of individual cells, and merely alert the operator to manually examine a blood smear by raising flags when abnormalities are detected. We demonstrate an automatic interferometry-based smear analysis technique known as diffraction phase cytometry (DPC), which is capable of providing the same information on red blood cells as is provided by current clinical analyzers, while rendering additional, currently unavailable parameters on the 2-D and 3-D morphology of individual red blood cells. To validate the utility of our technique in a clinical setting, we present a comparison between tests generated from 32 patients by a state of the art clinical impedance counter and DPC.