Project description:Bile duct cancer is the second most common primary liver cancer, with most diagnoses occurring in the advanced stages. This leads to a poor survival rate, which means a technique capable of reliably detecting pre-cancer in the bile duct is urgently required. Unfortunately, radiological imaging lacks adequate accuracy for distinguishing dysplastic and benign biliary ducts, while endoscopic techniques, which can directly assess the bile duct lining, often suffer from insufficient sampling. Here, we report an endoscopic optical light scattering technique for clinical evaluation of the malignant potential of the bile duct. This technique employs an ultraminiature spatial gating fiber optic probe compatible with cholangioscopes and endoscopic retrograde cholangiopancreatography (ERCP) catheters. The probe allowed us to investigate the internal cellular composition of the bile duct epithelium with light scattering spectroscopy (LSS) and phenotypic properties of the underlying connective tissue with diffuse reflectance spectroscopy (DRS). In a pilot in vivo double-blind prospective study involving 29 patients undergoing routine ERCP procedures, the technique detected malignant transformation with 97% accuracy, showing that biliary duct pre-cancer can be reliably identified in vivo non-invasively.
Project description:Esophageal adenocarcinoma is the most rapidly growing cancer in America. Although the prognosis after diagnosis is unfavorable, the chance of a successful outcome increases tremendously if detected early while the lesion is still dysplastic. Unfortunately, the present standard-of-care, endoscopic surveillance, has major limitations, since dysplasia is invisible, often focal, and systematic biopsies typically sample less than one percent of the esophageal lining and therefore easily miss malignancies. To solve this problem we developed a multispectral light scattering endoscopic imaging system. It surveys the entire esophageal lining and accurately detects subcellular dysplastic changes. The system combines light scattering spectroscopy, which detects and identifies invisible dysplastic sites by analyzing light scattered from epithelial cells, with rapid scanning of the entire esophageal lining using a collimated broadband light beam delivered by an endoscopically compatible fiber optic probe. Here we report the results of the first comprehensive multispectral imaging study, conducted as part of routine endoscopic procedures performed on patients with suspected dysplasia. In a double-blind study that characterized the system's ability to serve as a screening tool, 55 out of 57 patients were diagnosed correctly. In addition, a smaller double-blind comparison of the multispectral data in 24 patients with subsequent pathology at locations where 411 biopsies were collected yielded an accuracy of 90% in detecting individual locations of dysplasia, demonstrating the capability of this method to serve as a guide for biopsy.
Project description:Early and comprehensive endoscopic detection of colonic dysplasia - the most clinically significant precursor lesion to colorectal adenocarcinoma - provides an opportunity for timely, minimally-invasive intervention to prevent malignant transformation. Here, the development and evaluation of biodegradable near-infrared fluorescent silica nanoparticles (FSN) is described that have the potential to improve adenoma detection during fluorescence-assisted white-light colonoscopic surveillance in rodent and human-scale models of colorectal carcinogenesis. FSNs are biodegradable (t1/2 of 2.7 weeks), well-tolerated, and enable detection and delineation of adenomas as small as 0.5 mm2 with high tumor-to-background ratios. Furthermore, in the human-scale, APC1311/+ porcine model, the clinical feasibility and benefit of using FSN-guided detection of colorectal adenomas using video-rate fluorescence-assisted white-light endoscopy is demonstrated. Since nanoparticles of similar size (e.g., 100-150-nm) or composition (i.e., silica, silica/gold hybrid) have already been successfully translated to the clinic, and, clinical fluorescent/white light endoscopy systems are becoming more readily available, there is a viable path towards clinical translation of the proposed strategy for early colorectal cancer detection and prevention in high-risk patients.
Project description:Focusing light into scattering media, although challenging, is highly desirable in many realms. With the invention of time-reversed ultrasonically encoded (TRUE) optical focusing, acousto-optic modulation was demonstrated as a promising guidestar mechanism for achieving noninvasive and addressable optical focusing into scattering media. Here, we report a new ultrasound-assisted technique, ultrasound-induced field perturbation optical focusing, abbreviated as UFP. Unlike in conventional TRUE optical focusing, where only the weak frequency-shifted first-order diffracted photons due to acousto-optic modulation are useful, here UFP leverages the brighter zeroth-order photons diffracted by an ultrasonic guidestar as information carriers to guide optical focusing. We find that the zeroth-order diffracted photons, although not frequency-shifted, do have a field perturbation caused by the existence of the ultrasonic guidestar. By detecting and time-reversing the differential field of the frequency-unshifted photons when the ultrasound is alternately ON and OFF, we can focus light to the position where the field perturbation occurs inside the scattering medium. We demonstrate here that UFP optical focusing has superior performance to conventional TRUE optical focusing, which benefits from the more intense zeroth-order photons. We further show that UFP optical focusing can be easily and flexibly developed into double-shot realization or even single-shot realization, which is desirable for high-speed wavefront shaping. This new method upsets conventional thinking on the utility of an ultrasonic guidestar and broadens the horizon of light control in scattering media. We hope that it provides a more efficient and flexible mechanism for implementing ultrasound-guided wavefront shaping.
Project description:The investigators hypothesize that detection of field cancerization in the GI tract could be performed during endoscopy by performing Raman and scattering measurements. Together with the Technical University of Munich (TUM) and the Universidad Carlos III de Madrid (UC3M), the investigators have developed an investigational medical device that integrates probe-based Raman and scattering measurements for endoscopic purposes: the SENSITIVE system. During preclinical ex vivo studies, the investigators have established that measurements of the SENSITIVE system were able to discriminate between non-field cancerized tissue and field cancerized tissue. Considering these results, the investigators aim to assess the safety of in vivo Raman/scattering during endoscopy. Secondly, the investigators to assess the feasibility of this approach measurements to determine field cancerization in the alimentary tract during endoscopy through the SENSITIVE system.
Project description:Multijunction solar cells provide a path to overcome the efficiency limits of standard silicon solar cells by harvesting a broader range of the solar spectrum more efficiently. However, Si-based multijunction architectures are hindered by incomplete harvesting in the near-infrared (near-IR) spectral range as Si subcells have weak absorption close to the band gap. Here, we introduce an integrated near-field/far-field light trapping scheme to enhance the efficiency of silicon-based multijunction solar cells in the near-IR range. To achieve this, we design a nanopatterned diffractive silver back-reflector featuring a scattering matrix that optimizes trapping of multiply scattered light into a range of diffraction angles. We minimize reflection to the zeroth order and parasitic plasmonic absorption in silver by engineering destructive interference in the patterned back-contact. Numerical and experimental assessment of the optimal design on the performance of single-junction Si TOPCon solar cells highlights an improved external quantum efficiency over a planar back-reflector (+1.52 mA/cm2). Nanopatterned metagrating back-reflectors are fabricated on GaInP/GaInAsP//Si two-terminal triple-junction solar cells via substrate conformal imprint lithography and characterized optically and electronically, demonstrating a power conversion efficiency improvement of +0.9%abs over the planar reference. Overall, our work demonstrates the potential of nanophotonic light trapping for enhancing the efficiency of silicon-based multijunction solar cells, paving the way for more efficient and sustainable solar energy technologies.
Project description:Nanoparticles have become a powerful tool for cell imaging and biomolecule, cell and protein interaction studies, but are difficult to rapidly and accurately measure in most assays. Dark-field microscope (DFM) image analysis approaches used to quantify nanoparticles require high-magnification near-field (HN) images that are labor intensive due to a requirement for manual image selection and focal adjustments needed when identifying and capturing new regions of interest. Low-magnification far-field (LF) DFM imagery is technically simpler to perform but cannot be used as an alternate to HN-DFM quantification, since it is highly sensitive to surface artifacts and debris that can easily mask nanoparticle signal. We now describe a new noise reduction approach that markedly reduces LF-DFM image artifacts to allow sensitive and accurate nanoparticle signal quantification from LF-DFM images. We have used this approach to develop a "Dark Scatter Master" (DSM) algorithm for the popular NIH image analysis program ImageJ, which can be readily adapted for use with automated high-throughput assay analyses. This method demonstrated robust performance quantifying nanoparticles in different assay formats, including a novel method that quantified extracellular vesicles in patient blood sample to detect pancreatic cancer cases. Based on these results, we believe our LF-DFM quantification method can markedly decrease the analysis time of most nanoparticle-based assays to impact both basic research and clinical analyses.
Project description:Quantitative volumetric fluorescence imaging at high speed across a long term is vital to understand various cellular and subcellular behaviors in living organisms. Light-field microscopy provides a compact computational solution by imaging the entire volume in a tomographic way, while facing severe degradation in scattering tissue or densely-labelled samples. To address this problem, we propose an incoherent multiscale scattering model in a complete space for quantitative 3D reconstruction in complicated environments, which is called computational optical sectioning. Without the requirement of any hardware modifications, our method can be generally applied to different light-field schemes with reduction in background fluorescence, reconstruction artifacts, and computational costs, facilitating more practical applications of LFM in a broad community. We validate the superior performance by imaging various biological dynamics in Drosophila embryos, zebrafish larvae, and mice.
Project description:Here, we report the presence of defect-related states with magnetic degrees of freedom in crystals of LaAlO3 and several other rare-earth based perovskite oxides using inelastic light scattering (Raman spectroscopy) at low temperatures in applied magnetic fields of up to 9 T. Some of these states are at about 140 meV above the valence band maximum while others are mid-gap states at about 2.3 eV. No magnetic impurity could be detected in LaAlO3 by Proton-Induced X-ray Emission Spectroscopy. We, therefore, attribute the angular momentum-like states in LaAlO3 to cationic/anionic vacancies or anti-site defects. Comparison with the other rare earth perovskites leads to the empirical rule that the magnetic-field-sensitive transitions require planes of heavy elements (e.g. lanthanum) and oxygen without any other light cations in the same plane. These magnetic degrees of freedom in rare earth perovskites with useful dielectric properties may be tunable by appropriate defect engineering for magneto-optic applications.