Polarization-sensitive optical coherence tomography (PS-OCT) reveals the subsurface microstructure of biological tissue and provides information regarding the polarization state of light backscattered from tissue. Complementing OCT's structural signal with molecular imaging requires strategies to simultaneously detect multiple exogenous contrast agents with high specificity in tissue. Specific detection of molecular probes enables the parallel visualization of physiological, cellular, and molecular processes. Here we demonstrate that, by combining PS-OCT and spectral contrast (SC)-OCT measurements, we can distinguish signatures of different gold nanobipyramids (GNBPs) in lymphatic vessels from the surrounding tissue and blood vessels in live mouse models. This technique could ...

Visualization and evaluation of choroidal neovascularization (CNV) are major challenges to improve treatment outcomes for patients with age-related macular degeneration (AMD). Limitations of current imaging techniques include the limited penetration depth, spatial resolution, and sensitivity and difficulty visualizing CNV from the healthy microvasculature. In this study, a custom-built multimodal photoacoustic microscopy (PAM) and optical coherence tomography (OCT) system was developed to distinguish the margin of CNV in living rabbits with the assistance of functionalized gold nanorods conjugating with RGD ligands (GNR-RGD). Intravenous administration of GNR-RGD into rabbits in a CNV model resulted in signal enhancements of 27.2-fold in PAM ...

Multimodal optical imaging of tissue has significant potential to become an indispensable diagnostic tool in clinical pathology. Conventional bright-field microscopy provides contrast based on attenuation or reflectance of light, having no depth-related information and no molecular specificity. Recent developments in biomedical optics have introduced a variety of optical modalities, such as Raman spectroscopy (RS), fluorescence lifetime imaging microscopy (FLIM) of endogenous fluorophores, optical coherence tomography (OCT), and others, which provide a distinct characteristic, i.e., molecular, chemical, and morphological information, of the sample. To harvest the full analytical potential of those modalities, we have developed a novel multimodal imaging system ...

Stem cell regenerative medicine therapies have emerged as promising treatments for currently incurable diseases. A remaining challenge for cell therapies is the ability to track the migration and distribution of the transplanted cells in a long-term, noninvasive manner in vivo to assess their efficacy. This study develops a noninvasive, and high spatial resolution photoacoustic microscopy (PAM) and optical coherence tomography (OCT) imaging system for in vivo tracking of subretinally injected progenitor human retinal pigment epithelium cells (ARPE-19) labeled with chainlike gold nanoparticle (CGNP) clusters in RPE damage. CGNP provided significant PAM, OCT, and fluorescence signals to selectively track the migration ...

Advancing continuous health monitoring beyond vital signs to biochemistry will revolutionize personalized medicine. Herein, we report a biosensing platform to achieve remote biochemical monitoring using microparticle-based biosensors and optical coherence tomography (OCT). Stimuli-responsive, polymeric microparticles were designed to serve as freely dispersible biorecognition units, wherein binding with a target biochemical induces volumetric changes of the microparticle. Analytical approaches to detect these submicron changes in 3D using OCT were devised by modeling the microparticle as an optical cavity, enabling estimations far below the resolution of the OCT system. As a proof of concept, we demonstrated the 3D spatiotemporal monitoring of glucose-responsive ...

While photoacoustic microscopy (PAM) and optical coherence tomography (OCT) allow visualization of the retinal microvasculature, distinguishing early neovascularization from adjacent vessels remains challenging. Herein, gold nanostars (GNS) functionalized with RGD peptide were utilized as multimodality contrast agents for both PAM and OCT. GNS have great absorption and scattering characteristics in the near-infrared region where most vasculature and tissue generates less intrinsic photoacoustic signal while having a small size, excellent biocompatibility in vivo, and great photostability under nanosecond pulsed laser illumination. This enabled visualization and differentiation of individual microvasculature in vivo using multimodal PAM and OCT imaging. Detailed three-dimensional distribution of ...

Swept-source optical coherence tomography (SSOCT) is a non-contact, non-invasive bioimaging tool that usesvarious probes to get high contrast images. Rare-earth based upconversion particles (UCPs) providea uniqueplatform to enhance the capabilities of bioimaging techniques. The UCPs can act as contrast enhancers for SSOCT with additional optical functionality and hence in this work upconversion emission optimized PVP/NaGdF4:Er3+/Yb3+UCPs were synthesized and then injected to chicken breast tissues to enhance the SSOCT images. As synthesized samples have shown good biocompatibility towards HEK293, HeLa cell lines and showed apparent enhancement in contrast to SSOCT images. Additionally, compared to the bare NaGdF4 ...

In this study, an organic nano-drug delivery platform was constructed as a biocompatible cancer chemotherapeutic system, in which clini-cally approved sorafenib was loaded in the redox-responsive polymeric micelles, enabling dose-control release of drug to cancer tissues. In addition, visualizing tumor microenvironment changes is also essential for cancer chemotherapy, which can provide a priori and feedback control of drug delivery with reduced side effect. Therefore, second near-infrared window (NIR-II) dual-modal optical coherence tomogra-phy (OCT) and photoacoustic imaging were performed for real-time visualizing tumor microenvironment changes in vivo during chemo-therapy. In particular, the tumor angiogenesis, the vascular networks density change, and the ...

Optical coherence tomography (OCT) has gained wide adoption in biological research and medical imaging due to its exceptional tissue penetration, 3D imaging speed and rich contrast. However, OCT plays a relatively small role in molecular and cellular imaging due to the lack of suitable biomolecular contrast agents. In particular, while the green fluorescent protein has provided revolutionary capabilities to fluorescence microscopy by connecting it to cellular functions such as gene expression, no equivalent reporter gene is currently available for OCT. Here we introduce gas vesicles, a class of naturally evolved gas-filled protein nanostructures, as genetically encodable OCT contrast agents. The ...

Developing contrast-enhanced optical coherence tomography (OCT) techniques is important for specific imaging of tissue lesions, molecular imaging, cell-tracking, and highly sensitive microangiography and lymphangiography. Multiplexed OCT imaging in the second near infrared (NIR-II) window is highly desirable since it allows simultaneous imaging and tracking of multiple biological events in high resolution with deeper tissue penetration in vivo . Here we demonstrate that gold nanobipyramids can function as OCT multiplexing contrast agents, allowing high-resolution imaging of two separate lymphatic flows occurring simultaneously from different drainage basins into the same lymph node in a live mouse. Contrast-enhanced multiplexed lymphangiography of a melanoma tumor ...

By their nature, tumors pose a set of profound challenges to the immune system with respect to cellular recognition and response coordination. Recent research indicates that leukocyte subpopulations, especially tumor-associated macrophages (TAMs), can exert substantial influence on the efficacy of various cancer immunotherapy treatment strategies. To better study and understand the roles of TAMs in determining immunotherapeutic outcomes, significant technical challenges associated with dynamically monitoring single cells of interest in relevant live animal models of solid tumors must be overcome. However, imaging techniques with the requisite combination of spatiotemporal resolution, cell-specific contrast, and sufficient signal-to-noise at increasing depths in tissue ...

Magnetic/plasmonic hybrid nanoparticles are highly desirable for multimodal bioimaging and biosensing. Although the synthesis of heterodimeric nanoparticles has been reported, the products are usually hydrophobic so that post-treatment procedures are required to transfer them into water, which are often difficult to perform and cause damages to the structures. Direct synthesis of hydrophilic hybrid nanostructures has remained a grand challenge albeit its immediate advantage of biocompatibility. Herein we report a general seed-mediated approach to the synthesis of hydrophilic and biocompatible M-Fe 3 O 4 (M=Au, Ag and Pd) heterodimers, in which the size of metals and Fe 3 O ...

Optical coherence tomography (OCT) can be utilized with significant speckle reduction techniques and highly-scattering contrast agents for noninvasive, contrast-enhanced imaging of living tissues at the cellular scale. The advantages of reduced speckle noise and improved targeted contrast can be harnessed to track objects as small as 2 μm in vivo, which enables applications for cell tracking and quantification in living subjects. Here we demonstrate the use of Large Gold Nanorods (LGNRs) as contrast agents for detecting individual micron-sized polystyrene beads and single myeloma cells in blood circulation using speckle modulating-OCT (SM-OCT). This report marks the first time that OCT has ...

Optical coherence tomography angiography (OCTA) is an important tool for investigating vascular networks and microcirculation in living tissue. Traditional OCTA detects blood vessels via intravascular dynamic scattering signals derived from the movements of red blood cells (RBCs). However, the low hematocrit and long latency between RBCs in capillaries make these OCTA signals discontinuous, leading to incomplete mapping of the vascular networks. OCTA imaging of microvascular circulation is particularly challenging in tumors due to the abnormally slow blood flow in angiogenic tumor vessels and strong attenuation of light by tumor tissue. Here, we demonstrate in vivo that gold nanoprisms (GNPRs) can ...

This paper presents the design, fabrication, and characterization of Schottky graphene/silicon photodetectors that operate at a wavelength of 2 μm. These graphene/silicon junctions are carefully characterized using electric and optical measurements over the temperature range from 280–315 K. The photodetectors show external responsivity of 0.16 mA/W at room temperature under zero bias conditions, which is in excellent agreement with the theoretical predictions. In addition, the device performance is discussed in terms of the noise equivalent power and operating bandwidth. To the best of our knowledge, these are the first Si-based photodetectors designed for operation in ...

Herein, we report on biological imaging nanoprobes: physically-synthesized gold nanodisks that have inherent optical advantages—a wide range of resonant wavelengths, tunable ratio of light absorption-to-scattering, and responsiveness to random incident light—due to their two-dimensional circular nanostructure. Based on our proposed physical synthesis where gold is vacuum-deposited onto a pre-patterned polymer template and released from the substrate in the form of a nanodisk, monodisperse two-dimensional gold nanodisks were prepared with independent control of their diameter and thickness. The optical benefits of the Au nanodisk were successfully demonstrated by the measurement of light absorbance of the nanodisks and the application ...

In recent years, polymeric microneedles (MNs) have attracted keen interests among researchers for their applicability in transdermal drug delivery and interstitial skin fluid (ISF) extraction. When design and characterize such devices, it is critical to monitor their real-time in vitro and in vivo performances to optimize the desired effects, yet most of the existing methods are incapable of such functions. To address this unmet need, we develop a real-time non-invasive imaging methodology by integrating iron oxide (Fe3O4) nanoparticles into polymeric MNs to enhance image contrast for micro-optical coherence tomography (µOCT) imaging. Using the Fe3O4 integrated polystyrene-block-poly (acrylic acid) (PS-b-PAA) MNs ...

Ozone (O 3 ) would be harmful to human skin for its strong oxidizing property, especially when stratum corneum or corneal epithelium is wounded. Imaging the penetration and distribution of ozone at depth is beneficial for studying the influence of ozone on skin or eyes. Here, we introduced a facile method for three-dimensional (3D) imaging of the penetration of O 3 into the anterior chamber of an isolated crucian carp eye by using optical coherence tomography (OCT) combined with gold triangular nanoprisms (GTNPs) as the contrast agent and molecular probe. We illustrated the specific response of GTNPs to ozone and demonstrated ...

A single miniature endoscope capable of concurrently probing multiple contrast mechanisms of tissue in high resolution is highly attractive, as it makes it possible for providing complementary, more complete tissue information on internal organs hard to access. Here we describe such a miniature endoscope only 1 mm in diameter that integrates photoacoustic imaging (PAI), optical coherence tomography (OCT), and ultrasound (US). The integration of PAI/OCT/US allows for high-resolution imaging of three tissue contrasts including optical absorption (PAI), optical scattering (OCT), and acoustic properties (US). We demonstrate the capabilities of this trimodal endoscope using mouse ear, human hand, and ...

The development of novel tools for studying the fouling behavior during membrane processes is critical. This work explored optical coherence tomography (OCT) to quantitatively interpret the formation of a cake layer during a membrane process; the quantitative analysis was based on a novel image processing method that was able to precisely resolve the 3D structure of the cake layer on a micron scale. Fouling experiments were carried out with foulants having different physicochemical characteristics (silica nanoparticles and bentonite particles). The cake layers formed at a series of times were digitalized using the OCT-based characterization. The specific deposit (cake volume/membrane ...

Mechanical and structural properties of biofilms influence the accumulation and release of pathogens in drinking water distribution systems (DWDS). Thus, understanding how long-term residual disinfectants exposure affects biofilm mechanical and structural properties is a necessary aspect for pathogen risk assessment and control. In this study, elastic modulus and structure of groundwater biofilms was monitored by atomic force microscopy (AFM) and optical coherence tomography (OCT) during three months of exposure to monochloramine or free chlorine. After the first month of disinfectant exposure, the mean stiffness of monochloramine or free chlorine treated biofilms was 4 to 9 times higher than those before ...

Gold nanorods (GNRs, ~50 x 15 nm) have been used ubiquitously in biomedicine for their optical properties, and many biofunctionalization methods have been described for them. Recently, the synthesis of larger-than-usual GNRs (LGNRs, ~100 x 30 nm) has been demonstrated. However, LGNRs have not been biofunctionalized and therefore remain absent from biomedical literature to date. Here we report the first biofunctionalization of LGNRs, resulting in highly stable particles with a narrow spectral peak (FWHM ~100 nm). We further demonstrated that functionalized LGNRs can be used as highly sensitive contrast agents for Optical Coherence Tomography (OCT), visualizing individual LGNRs in clear ...

Biofilms in drinking water distribution systems (DWDS) could exacerbate the persistence and associated risks of pathogenic Legionella pneumophila, thus raising human health concerns. However, mechanisms controlling adhesion and subsequent detachment of L. pneumophila associated with biofilms remain unclear. We determined the connection between L. pneumophila adhesion and subsequent detachment with biofilm physical structure characterization using optical coherence tomography (OCT) imaging technique. Analysis of the OCT images of multi-species biofilms grown under low nutrient condition up to 29 weeks revealed the lack of biofilm deformation even when these biofilms were exposed to flow velocity of 0.7 m/s, typical flow ...

Fouling control is one of the critical issues in membrane filtration and plays a very important role in water/wastewater treatment. Better understanding of the underlying fouling mechanisms entails novel characterization techniques that can realize a real-time non-invasive observation and provide high resolution images recording the formation of a fouling layer . This work presents a characterization method based on optical coherence tomography (OCT), which is able to detect the internal structures and motions by analyzing the interference signals. An OCT system was incorporated with a lab-scale membrane filtration system, and the growth of the fouling layer was observed by using ...