Abstract: The presently disclosed subject matter provides methods using mass spectrometry for direct profiling of N-linked glycans from a biological sample. In addition, the embodiments of the present invention also disclose novel methods, known as targeted analyte detection (TAD), for improving the detection limit of MALDI-MS. These methods take advantage of the carrier effect of the added standard analytes, which occurs due to the generic sigmoidal shape of the calibration curve. The functionality of TAD depends on the relative enhancement of sensitivity over the increase of the standard deviation at the analysis of target analytes with spiking in exogenous concentration. At certain ranges of exogenous concentration, the increment in the sensitivity overcomes the standard deviation, resulting in an improved LOD. Theoretically, exogenous concentrations approximately at 1 LODorig would generate the optimum LOD improvement.

Abstract: The present invention is directed to an achromatic endoscope which employs a diffractive microlens. Along with a broadband rotary joint and a custom 800 nm SD-OCT system, ultrahigh-resolution 3D volumetric imaging over a large area becomes possible. The diffractive microlens can be used directly with a GRIN lens, making the endoscope design simpler and cost effective. Preliminary ex vivo 3D intraluminal imaging was performed with the endoscope in conjunction with a home-built broadband rotary joint and a spectral-domain OCT system, demonstrating the performance of the diffractive endoscope. Considering the miniature OCT imaging probe is the required component for using the OCT technology in internal organs, the proposed approach will have a broad impact on endoscopic OCT imaging by improving OCT resolution in any applications that involve a miniature OCT probe, as intravascular OCT imaging, gastrointestinal (GI) tract imaging, airway imaging etc.

Abstract: The presently disclosed subject matter provides methods using mass spectrometry for direct profiling of N-linked glycans from a biological sample. In addition, the embodiments of the present invention also disclose novel methods, known as targeted analyte detection (TAD), for improving the detection limit of MALDI-MS. These methods take advantage of the carrier effect of the added standard analytes, which occurs due to the generic sigmoidal shape of the calibration curve. The functionality of TAD depends on the relative enhancement of sensitivity over the increase of the standard deviation at the analysis of target analytes with spiking in exogenous concentration. At certain ranges of exogenous concentration, the increment in the sensitivity overcomes the standard deviation, resulting in an improved LOD. Theoretically, exogenous concentrations approximately at 1 LODorig would generate the optimum LOD improvement.

Abstract: The present invention is directed to an achromatic capsule endoscope with diffractive optics. A micromotor (or a broadband rotary joint) and a custom 800 nm SD-OCT system make ultrahigh-resolution 3D volumetric imaging over a large area possible. The diffractive microlens is used directly with other miniature lens including but not limited to a GRIN lens, making the capsule endoscope design simpler and cost effective. Preliminary ex vivo 3D intraluminal imaging was performed with the distal-scanning capsule endoscope in conjunction with a home-built broadband spectral-domain OCT system, demonstrating the performance of the diffractive capsule.

Abstract: The presently disclosed subject matter provides methods using mass spectrometry for direct profiling of N-linked glycans from a biological sample. In addition, the embodiments of the present invention also disclose novel methods, known as targeted analyte detection (TAD), for improving the detection limit of MALDI-MS. These methods take advantage of the carrier effect of the added standard analytes, which occurs due to the generic sigmoidal shape of the calibration curve. The functionality of TAD depends on the relative enhancement of sensitivity over the increase of the standard deviation at the analysis of target analytes with spiking in exogenous concentration. At certain ranges of exogenous concentration, the increment in the sensitivity overcomes the standard deviation, resulting in an improved LOD. Theoretically, exogenous concentrations approximately at 1 LODorig would generate the optimum LOD improvement.

Abstract: The presently disclosed subject matter provides methods using mass spectrometry for direct profiling of N-linked glycans from a biological sample. In addition, the embodiments of the present invention also disclose novel methods, known as targeted analyte detection (TAD), for improving the detection limit of MALDI-MS. These methods take advantage of the carrier effect of the added standard analytes, which occurs due to the generic sigmoidal shape of the calibration curve. The functionality of TAD depends on the relative enhancement of sensitivity over the increase of the standard deviation at the analysis of target analytes with spiking in exogenous concentration. At certain ranges of exogenous concentration, the increment in the sensitivity overcomes the standard deviation, resulting in an improved LOD. Theoretically, exogenous concentrations approximately at 1 LODorig would generate the optimum LOD improvement.

Abstract: The present invention is directed to a fiber optic device that enables multiphoton imaging with improved signal-to-noise ratio having a single piece of double-clad fiber (DCF). The device also includes all components for focusing, scanning and signal collection within an endomicroscope probe of 2.1 mm outer diameter (OD). The unprecedented imaging capability of this miniature endomicroscope is demonstrated herein via both ex vivo and in vivo experiments.

Abstract: The present invention is directed to a method for real-time characterization of spatially-resolved tissue optical properties using OCT/LCI. Imaging data are acquired, processed, displayed and stored in real-time. The resultant tissue optical properties are then used to determine the diagnostic threshold and to determine the OCT/LCI detection sensitivity and specificity. Color-coded optical property maps are constructed to provide direct visual cues for surgeons to differentiate tumor versus non-tumor tissue. These optical property maps can be overlaid with the structural imaging data and/or Doppler results for efficient data display. Finally, the imaging system can also be integrated with existing systems such as tracking and surgical microscopes. An aiming beam is generally provided for interventional guidance. For intraoperative use, a cap/spacer may also be provided to maintain the working distance of the probe, and also to provide biopsy capabilities.

Abstract: The present invention is directed to a fiber optic device that enables multiphoton imaging with improved signal-to-noise ratio having a single piece of double-clad fiber (DCF). The device also includes all components for focusing, scanning and signal collection within an endomicroscope probe of 2.1 mm outer diameter (OD). The unprecedented imaging capability of this miniature endomicroscope is demonstrated herein via both ex vivo and in vivo experiments.

Abstract: The present invention is directed to an achromatic endoscope which employs a diffractive microlens. Along with a broadband rotary joint and a custom 800 nm SD-OCT system, ultrahigh-resolution 3D volumetric imaging over a large area becomes possible. The diffractive microlens can be used directly with a GRIN lens, making the endoscope design simpler and cost effective. Preliminary ex vivo 3D intraluminal imaging was performed with the endoscope in conjunction with a home-built broadband rotary joint and a spectral-domain OCT system, demonstrating the performance of the diffractive endoscope. Considering the miniature OCT imaging probe is the required component for using the OCT technology in internal organs, the proposed approach will have a broad impact on endoscopic OCT imaging by improving OCT resolution in any applications that involve a miniature OCT probe, as intravascular OCT imaging, gastrointestinal (GI) tract imaging, airway imaging etc.

Abstract: The presently disclosed subject matter provides methods using mass spectrometry for direct profiling of N-linked glycans from a biological sample. In addition, the embodiments of the present invention also disclose novel methods, known as targeted analyte detection (TAD), for improving the detection limit of MALDI-MS. These methods take advantage of the carrier effect of the added standard analytes, which occurs due to the generic sigmoidal shape of the calibration curve. The functionality of TAD depends on the relative enhancement of sensitivity over the increase of the standard deviation at the analysis of target analytes with spiking in exogenous concentration. At certain ranges of exogenous concentration, the increment in the sensitivity overcomes the standard deviation, resulting in an improved LOD. Theoretically, exogenous concentrations approximately at 1 LODorig would generate the optimum LOD improvement.

Abstract: The present invention is directed to an all-fiber-optic scanning endomicroscope capable of high-resolution second harmonic generation (SHG) imaging of biological tissues. The endomicroscope has an overall 2.0 mm diameter and consists of a single customized double-clad fiber, a compact rapid two-dimensional beam scanner, and a miniature compound objective lens for excitation beam delivery, scanning, focusing, and efficient SHG signal collection. Endomicroscopic SHG images of murine cervical tissue sections at different stages of normal pregnancy reveal progressive, quantifiable changes in cervical collagen morphology with resolution similar to that of bench-top SHG microscopy. A device according to an embodiment of the present invention can also be used to assess other pathologies, such as cancer. fibrosis, and inflammation. The present invention allows for diagnosis, monitoring of the effect of therapeutics, and surgical or interventional guidance.

Abstract: Mechanically robust minimal form factor OCT probes suitable for medical applications such as needle biopsy, intraluminal and intravascular imaging are achieved in part by employing compound lenses with some or all of the optical elements, including an optical fiber, to be thermally fused in tandem. To achieve a desired working distance without increasing a diameter of the optics assembly, a spacer can be disposed between the optical fiber and focusing optics. The compound lens configuration can achieve higher transverse resolution compared to a single lens at a desired working distance without increasing the probe diameter. In exemplary needle biopsy embodiments, the optical assembly is encapsulated in a glass housing or metal-like housing with a glass window, which is then selectively passed through a hollow needle. Esophageal imaging embodiments are combined with a balloon catheter. Circumferential and three-dimensional spiral scanning can be achieved in each embodiment.

Abstract: Mechanically robust minimal form factor OCT probes suitable for medical applications such as needle biopsy, intraluminal and intravascular imaging are achieved in part by employing compound lenses with some or all of the optical elements, including an optical fiber, to be thermally fused in tandem. To achieve a desired working distance without increasing a diameter of the optics assembly, a spacer can be disposed between the optical fiber and focusing optics. The compound lens configuration can achieve higher transverse resolution compared to a single lens at a desired working distance without increasing the probe diameter. In exemplary needle biopsy embodiments, the optical assembly is encapsulated in a glass housing or metal-like housing with a glass window, which is then selectively passed through a hollow needle. Esophageal imaging embodiments are combined with a balloon catheter. Circumferential and three-dimensional spiral scanning can be achieved in each embodiment.

Abstract: An optical fiber scanner is used for multiphoton excitation imaging, optical coherence tomography, or for confocal imaging in which transverse scans are carried out at a plurality of successively different depths within tissue. The optical fiber scanner is implemented as a scanning endoscope using a cantilevered optical fiber that is driven into resonance or near resonance by an actuator. The actuator is energized with drive signals that cause the optical fiber to scan in a desired pattern at successively different depths as the depth of the focal point is changed. Various techniques can be employed for depth focus tracking at a rate that is much slower than the transverse scanning carried out by the vibrating optical fiber. The optical fiber scanner can be used for confocal imaging, multiphoton fluorescence imaging, nonlinear harmonic generation imaging, or in an OCT system that includes a phase or frequency modulator and delay line.

Abstract: Method and apparatus for achieving dynamic focus tracking during real-time optical coherence tomography (OCT) by simultaneously implementing geometric focus tracking (GFT) and coherence gate tracking (CGT). GFT tracking involves changing a position of the focal point of the OCT probe in the sample during scanning. Preferably, the focal point is moved relative to the sample without disrupting the Gaussian beam profile of the scanner. CGT involves determining a change in the optical path length of the sample arm due to the GFT, and calculating the change in the optical path length in the reference arm required to maintain an equivalent optical path length in both the sample arm and the reference arm. The reference arm is then translated by the required amount, to maximize the OCT signal. A lateral priority scanning technique is employed, and this technique can be implemented using a single optical fiber suitable for endoscopic use.

Abstract: In Optical Doppler tomography (ODT), or color Doppler optical coherence tomography, the signal component of primary interest arises from moving scatterers, such as flowing blood cells in blood vessels. Clutter rejection filters are provided and used to remove undesired components from the ODT signal, such as clutter induced by stationary scatterers (e.g., the relatively stationary tissue of a blood vessel wall). Empirical results indicate that such clutter rejection filters can be employed to achieve ODT images from which blood vessel diameter can more accurately be estimated than images obtained using conventional ODT techniques. Further, Doppler images obtained using the clutter rejection filter technique disclosed herein exhibit fewer background artifacts induced by the relative motion of stationary scatterers with respect to the scanning probe.

Abstract: A miniature, flexible, fiber-optic scanning endoscope for nonlinear optical imaging and spectroscopy. The endoscope uses a tubular piezoelectric actuator for activating a cantilevered optical fiber from which pulsed light produced by a laser source exits and is directed to a target region through a micro-lens. The actuator is activated by two modulated signals that achieve two-dimensional beam scanning in a desired scan pattern. A double-clad optical fiber is employed for delivery of the excitation pulsed light and collection of emitted light received from the target region. The pulsed light travels through a core of the double-clad optical fiber, and the emitted light from the target region is directed into the core and inner cladding of the optical fiber and conveyed to a proximal end, for detection and processing. The emitted light can include multiphoton fluorescence, second harmonic generation light, and spectroscopic information, for use in imaging.

Abstract: Method and apparatus for achieving dynamic focus tracking during real-time optical coherence tomography (OCT) by simultaneously implementing geometric focus tracking (GFT) and coherence gate tracking (CGT). GFT tracking involves changing a position of the focal point of the OCT probe in the sample during scanning. Preferably, the focal point is moved relative to the sample without disrupting the Gaussian beam profile of the scanner. CGT involves determining a change in the optical path length of the sample arm due to the GFT, and calculating the change in the optical path length in the reference arm required to maintain an equivalent optical path length in both the sample arm and the reference arm. The reference arm is then translated by the required amount, to maximize the OCT signal. A lateral priority scanning technique is employed, and this technique can be implemented using a single optical fiber suitable for endoscopic use.

Abstract: An optical fiber scanner is used for multiphoton excitation imaging, optical coherence tomography, or for confocal imaging in which transverse scans are carried out at a plurality of successively different depths within tissue. The optical fiber scanner is implemented as a scanning endoscope using a cantilevered optical fiber that is driven into resonance or near resonance by an actuator. The actuator is energized with drive signals that cause the optical fiber to scan in a desired pattern at successively different depths as the depth of the focal point is changed. Various techniques can be employed for depth focus tracking at a rate that is much slower than the transverse scanning carried out by the vibrating optical fiber. The optical fiber scanner can be used for confocal imaging, multiphoton fluorescence imaging, nonlinear harmonic generation imaging, or in an OCT system that includes a phase or frequency modulator and delay line.