Fiber-optic Methods and Devices Enabling Multiphoton Imaging with Improved Signal-to-Noise Ratio

We report the development of a single-fiber based scanning device (termed as endomicroscope) and system capable of performing high-resolution optical imaging of biological tissues with multiphoton excitation. The imaging device is fiber-optically based and is flexible with a small footprint (~2 mm in diameter), and the entire imaging system is compact and portable. The technology can serve as (1) a transformative clinical tool for performing multiphoton imaging of internal organs that are not possible with a standard microscope; and (2) a research tool with flexibility and dramatically reduced cost (by a factor 100-200) when compared with a bench-top multiphoton imaging system. The endomicroscopy technology can function as a new form of histology by enabling visualization of tissue microstructures at histology resolution in vivo, in situ and in real time but without the need for tissue removal. Technological innovations reported in this disclosure also made it possible to image biological tissues even without the use of exogenous dyes, i.e. by using only intrinsic fluorescent molecules, absorption molecules and structural proteins. Thus label-free imaging is feasible. The fiber-optic endomicroscope can be very cost-effective and disposable. The major IPs include the method for engineering such an extremely compact, single-fiber based scanning endomicroscope, methods for achieving a sufficient signal to noise ratio to enable tissue imaging (without the need for staining dyes, i.e. label-free), and methods for achieving high-resolution with micro optics.

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