Multimodal Non-Linear Microscopy Combines CARS, SHG and TPEF

Multimodal Non-Linear Microscopy Combines CARS, SHG and TPEF

Multimodal non-linear microscopy, combining coherent anti-Stokes Raman scattering (CARS), second harmonic generation (SHG), and two-photon excited fluorescence (TPEF), provides non-invasive and label-free information on the molecular composition and morphology of biological specimens ex vivo, enabling the detection of diseases.

A paper describing the development of such a detection system is entitled, “Multimodal nonlinear endomicroscopic imaging probe using a double-core double-clad fiber and focus-combining micro-optical concept.”

Here is the Abstract of the paper:

Multimodal non-linear microscopy combining coherent anti-Stokes Raman scattering, second harmonic generation, and two-photon excited fluorescence has proved to be a versatile and powerful tool enabling the label-free investigation of tissue structure, molecular composition, and correlation with function and disease status. For a routine medical application, the implementation of this approach into an in vivo imaging endoscope is required. However, this is a difficult task due to the requirements of a multicolour ultrashort laser delivery from a compact and robust laser source through a fiber with low losses and temporal synchronization, the efficient signal collection in epi-direction, the need for small-diameter but highly corrected endomicroobjectives of high numerical aperture and compact scanners. Here, we introduce an ultra-compact fiber-scanning endoscope platform for multimodal non-linear endomicroscopy in combination with a compact four-wave mixing based fiber laser. The heart of this fiber-scanning endoscope is an in-house custom-designed, single mode, double clad, double core pure silica fiber in combination with a 2.4 mm diameter NIR-dual-waveband corrected endomicroscopic objective of 0.55 numerical aperture and 180 µm field of view for non-linear imaging, allowing a background free, low-loss, high peak power laser delivery, and an efficient signal collection in backward direction. A linear diffractive optical grating overlays pump and Stokes laser foci across the full field of view, such that diffraction-limited performance is demonstrated for tissue imaging at one frame per second with sub-micron spatial resolution and at a high transmission of 65% from the laser to the specimen using a distal resonant fiber scanner.

GRINTECH supplied the objective lens for the endoscope used in this research.

About GRINTECH

GRINTECH is a leading manufacturer of GRadient INdex (GRIN) micro-optic lenses and lens systems. These miniaturized lenses provide extraordinarily good optical performance and flat optical surfaces. (See the Explanation of the physics of GRIN lenses.)

The optical power of GRIN lenses is achieved by a refractive index profile fabricated in glass by a non-toxic, silver-and-lithium-ion-exchange process. These unique rod and cylindrical micro-lenses have typical diameters from 200 µm to 2 mm.

The GRINTECH catalog includes:

• GRIN rods used for fiber and laser diode collimation and beam shaping
• Lenses and assemblies for clinical and industrial endoscopic applications
• Needle imaging assemblies and miniature high-NA objectives for in-vivo endomicroscopy and related accessories

These products are used for medical imaging and biophotonic technology, optical metrology, and sensor technology for applications such as brain imaging and endomicroscopy. In addition, GRINTECH develops, fabricates, and delivers high quality, reliable, custom-made modules and assemblies, tailored to the specific needs of customer applications. These assemblies and subassemblies are often inspired by or based on GRINTECH’s standard products.

To support industrial customers, GRINTECH’s team of optical designers and mechanical engineers design and produce more complex optical sensors, focusing or deflecting modules, imaging assemblies consisting of mechanical housings and mounts, optical fibers, prisms, beam splitters, laser diodes, etc., which are combined with GRIN and other lenses.

Customizations include: fiber type, length, buffer, connector type, prism size, stainless steel tube mounts, angled fiber end face, coatings, design wavelengths, spot or image working distance, spot size and numerical aperture, etc.

For more information or a quotation for GRINTECH products, contact IL Photonics.