Ultra-thin and flexible endoscopy probe for optical coherence tomography based on stepwise transitional core fiber

We present an ultra-thin fiber-body endoscopy probe for optical coherence tomography (OCT) which is based on a stepwise transitional core (STC) fiber. In a minimalistic design, our probe was made of spliced specialty fibers that could be directly used for beam probing optics without using a lens. In our probe, the OCT light delivered through a single-mode fiber was efficiently expanded to a large mode field of 24 μm diameter for a low beam divergence. The size of our probe was 85 μm in the probe’s diameter while operated in a 160-μm thick protective tubing. Through theoretical and experimental analyses, our probe was found to exhibit various attractive features in terms of compactness, flexibility and reliability along with its excellent fabrication simplicity.OCIS codes: (110.4500) Optical coherence tomography, (170.2150) Endoscopic imaging, (170.3890) Medical optics instrumentation, (060.2350) Fiber optics imaging     

Time-shared optical tweezers with a microlens array for dynamic microbead arrays

Dynamic arrays of microbeads and cells offer great flexibility and potential as platforms for sensing and manipulation applications in various scientific fields, especially biology and medicine. Here, we present a simple method for assembling and manipulating dense dynamic arrays based on time-shared scanning optical tweezers with a microlens array. Three typical examples, including the dynamic and simultaneous bonding of microbeads in real-time, are demonstrated. The optical design and the hardware setup for our approach are also described.OCIS codes: (350.4855) Optical tweezers or optical manipulation, (140.7010) Laser trapping, (170.4520) Optical confinement and manipulation, (170.0170) Medical optics and biotechnology     

Fiber based optical tweezers for simultaneous in situ force exertion and measurements in a 3D polyacrylamide gel compartment

Optical tweezers play an important role in biological applications. However, it is difficult for traditional optical tweezers based on objective lenses to work in a three-dimensional (3D) solid far away from the substrate. In this work, we develop a fiber based optical trapping system, namely inclined dual fiber optical tweezers, that can simultaneously apply and measure forces both in water and in a 3D polyacrylamide gel matrix. In addition, we demonstrate in situ, non-invasive characterization of local mechanical properties of polyacrylamide gel by measurements on an embedded bead. The fiber optical tweezers measurements agree well with those of atomic force microscopy (AFM). The inclined dual fiber optical tweezers provide a promising and versatile tool for cell mechanics study in 3D environments.OCIS codes: (350.4855) Optical tweezers or optical manipulation, (060.2310) Fiber optics     

Controlled 3D rotation of biological cells using optical multiple-force clamps

Controlled three-dimensional (3D) rotation of arbitrarily shaped objects in the observation space of optical microscopes is essential for realizing tomographic microscope imaging and offers great flexibility as a noncontact micromanipulation tool for biomedical applications. Herein, we present 3D rotational control of inhomogeneous biological samples using 3D optical multiple-force clamps based on time-shared scanning with a fast focus-tunable lens. For inhomogeneous samples with shape and optical anisotropy, we choose diatoms and their fragments, and demonstrate interactive and controlled 3D rotation about arbitrary axes in 3D Cartesian coordinates. We also outline the hardware setup and 3D rotation method for our demonstrations.OCIS codes: (350.4855) Optical tweezers or optical manipulation, (140.7010) Laser trapping, (170.4520) Optical confinement and manipulation, (170.0170) Medical optics and biotechnology     

Molecular imaging needles: dual-modality optical coherence tomography and fluorescence imaging of labeled antibodies deep in tissue

Molecular imaging using optical techniques provides insight into disease at the cellular level. In this paper, we report on a novel dual-modality probe capable of performing molecular imaging by combining simultaneous three-dimensional optical coherence tomography (OCT) and two-dimensional fluorescence imaging in a hypodermic needle. The probe, referred to as a molecular imaging (MI) needle, may be inserted tens of millimeters into tissue. The MI needle utilizes double-clad fiber to carry both imaging modalities, and is interfaced to a 1310-nm OCT system and a fluorescence imaging subsystem using an asymmetrical double-clad fiber coupler customized to achieve high fluorescence collection efficiency. We present, to the best of our knowledge, the first dual-modality OCT and fluorescence needle probe with sufficient sensitivity to image fluorescently labeled antibodies. Such probes enable high-resolution molecular imaging deep within tissue.OCIS codes: (170.0180) Microscopy, (170.4500) Optical coherence tomography, (170.2520) Fluorescence microscopy, (110.2350) Fiber optics imaging     

Imaging of a linear diode bar for an optical cell stretcher

We present a simplified approach for imaging a linear diode bar laser for application as an optical stretcher within a microfluidic geometry. We have recently shown that these linear sources can be used to measure cell mechanical properties; however, the source geometry creates imaging challenges. To minimize intensity losses and simplify implementation within microfluidic systems without the use of expensive objectives, we combine aspheric and cylindrical lenses to create a 1:1 image of the source at the stretcher focal plane and demonstrate effectiveness by measuring the deformation of human red blood cells and neutrophils.OCIS codes: (140.2020) Diode lasers, (140.7010) Laser trapping, (140.5960) Semiconductor lasers, (170.4520) Optical confinement and manipulation, (170.1530) Cell analysis, (170.0180) Microscopy, (170.0170) Medical optics and biotechnology, (350.4855) Optical tweezers or optical manipulation     

Miniature forward-viewing common-path OCT probe for imaging the renal pelvis

We demonstrate an ultrathin flexible cone-scanning forward-viewing OCT probe which can fit through the working channel of a flexible ureteroscope for renal pelvis imaging. The probe is fabricated by splicing a 200 µm section of core-less fiber and a 150 µm section of gradient-index (GRIN) fiber to the end of a single mode (SM) fiber. The probe is designed for common-path OCT imaging where the back-reflection of the GRIN fiber/air interface is used as the reference signal. Optimum sensitivity was achieved with a 2 degree polished probe tip. A correlation algorithm was used to correct image distortion caused by non-uniform rotation of the probe. The probe is demonstrated by imaging human skin in vivo and porcine renal pelvis ex vivo and is suitable for imaging the renal pelvis in vivo for cancer staging.OCIS codes: (110.4500) Optical coherence tomography, (170.2150) Endoscopic imaging, (170.3890) Medical optics instrumentation     

Laser tissue coagulation and concurrent optical coherence tomography through a double-clad fiber coupler

Double-clad fiber (DCF) is herein used in conjunction with a double-clad fiber coupler (DCFC) to enable simultaneous and co-registered optical coherence tomography (OCT) and laser tissue coagulation. The DCF allows a single channel fiber-optic probe to be shared: i.e. the core propagating the OCT signal while the inner cladding delivers the coagulation laser light. We herein present a novel DCFC designed and built to combine both signals within a DCF (>90% of single-mode transmission; >65% multimode coupling). Potential OCT imaging degradation mechanisms are also investigated and solutions to mitigate them are presented. The combined DCFC-based system was used to induce coagulation of an ex vivo swine esophagus allowing a real-time assessment of thermal dynamic processes. We therefore demonstrate a DCFC-based system combining OCT imaging with laser coagulation through a single fiber, thus enabling both modalities to be performed simultaneously and in a co-registered manner. Such a system enables endoscopic image-guided laser marking of superficial epithelial tissues or laser thermal therapy of epithelial lesions in pathologies such as Barrett’s esophagus.OCIS codes: (060.2340) Fiber optics components, (170.2150) Endoscopic imaging, (170.3880) Medical and biological imaging, (170.3890) Medical optics instrumentation, (170.4500) Optical coherence tomography     

Optical vortices generated by a PANDA ring resonator for drug trapping and delivery applications

We propose a novel drug delivery system (DDS) by using a PANDA ring resonator to form, transmit and receive the microscopic volume by controlling some suitable ring parameters. The optical vortices (gradient optical field/well) can be generated and used to form the trapping tool in the same way as the optical tweezers. The microscopic volume (drug) can be trapped and moved (transported) dynamically within the wavelength router or network. In principle, the trapping force is formed by the combination between the gradient field and scattering photons, which has been reviewed. The advantage of the proposed system is that a transmitter and receiver can be formed within the same system, which is called transceiver, in which the use of such a system for microscopic volume (drug volume) trapping and transportation (delivery) can be realized.OCIS codes: (140.7010) Laser trapping, (350.4855) Optical tweezers or optical manipulation, (080.4865) Optical vortices, (140.4780) Optical resonators, (190.4360) Nonlinear optics, devices     

Motion-compensated hand-held common-path Fourier-domain optical coherence tomography probe for image-guided intervention

A motion-compensated, hand-held, common-path, Fourier-domain optical coherence tomography imaging probe has been developed for image-guided intervention during microsurgery. A hand-held prototype instrument was achieved by integrating an imaging fiber probe inside a stainless steel needle and attached to the ceramic shaft of a piezoelectric motor housed in an aluminum handle. The fiber probe obtains A-scan images. The distance information was extracted from the A-scans to track the sample surface distance and a fixed distance was maintained by a feedback motor control which effectively compensated hand tremor and target movements in the axial direction. Real-time data acquisition, processing, motion compensation, and image visualization and saving were implemented on a custom CPU-GPU hybrid architecture. We performed 10× zero padding to the raw spectrum to obtain 0.16 µm position accuracy with a compensation rate of 460 Hz. The root-mean-square error of hand-held distance variation from target position was measured to be 2.93 µm. We used a cross-correlation maximization-based shift correction algorithm for topology correction. To validate the system, we performed free-hand OCT M-scan imaging using various samples.OCIS codes: (100.2000) Digital image processing, (110.4500) Optical coherence tomography, (170.3890) Medical optics instrumentation     

Retinal nerve fiber bundle tracing and analysis in human eye by polarization sensitive OCT

We present a new semi-automatic processing method for retinal nerve fiber bundle tracing based on polarization sensitive optical coherence tomography (PS-OCT) data sets. The method for tracing is based on a nerve fiber orientation map that covers the fovea and optic nerve head (ONH) regions. In order to generate the orientation map, two types of information are used: optic axis orientation based on polarization data, and complementary information obtained from nerve fiber layer (NFL) local thickness variation to reveal fiber bundle structures around the fovea. The corresponding two orientation maps are fused into a combined fiber orientation map. En face maps of NFL retardation, thickness, and unit-depth-retardation (UDR, equivalent to birefringence) are transformed into “along-trace” maps by using the obtained traces of the nerve fiber bundles. The method is demonstrated in the eyes of healthy volunteers, and as an example of further analyses utilizing this method, maps illustrating the gradients of NFL retardation, thickness, and UDR are demonstrated.OCIS codes: (170.0170) Medical optics and biotechnology, (170.0110) Imaging systems, (170.2655) Functional monitoring and imaging, (170.4470) Ophthalmology, (170.4500) Optical coherence tomography     

Dual instrument for in vivo and ex vivo OCT imaging in an ENT department

A dual instrument is assembled to investigate the usefulness of optical coherence tomography (OCT) imaging in an ear, nose and throat (ENT) department. Instrument 1 is dedicated to in vivo laryngeal investigation, based on an endoscope probe head assembled by compounding a miniature transversal flying spot scanning probe with a commercial fiber bundle endoscope. This dual probe head is used to implement a dual channel nasolaryngeal endoscopy-OCT system. The two probe heads are used to provide simultaneously OCT cross section images and en face fiber bundle endoscopic images. Instrument 2 is dedicated to either in vivo imaging of accessible surface skin and mucosal lesions of the scalp, face, neck and oral cavity or ex vivo imaging of the same excised tissues, based on a single OCT channel. This uses a better interface optics in a hand held probe. The two instruments share sequentially, the swept source at 1300 nm, the photo-detector unit and the imaging PC. An aiming red laser is permanently connected to the two instruments. This projects visible light collinearly with the 1300 nm beam and allows pixel correspondence between the en face endoscopy image and the cross section OCT image in Instrument 1, as well as surface guidance in Instrument 2 for the operator. The dual channel instrument was initially tested on phantom models and then on patients with suspect laryngeal lesions in a busy ENT practice. This feasibility study demonstrates the OCT potential of the dual imaging instrument as a useful tool in the testing and translation of OCT technology from the lab to the clinic. Instrument 1 is under investigation as a possible endoscopic screening tool for early laryngeal cancer. Larger size and better quality cross-section OCT images produced by Instrument 2 provide a reference base for comparison and continuing research on imaging freshly excised tissue, as well as in vivo interrogation of more superficial skin and mucosal lesions in the head and neck patient.OCIS codes: (170.4500) Optical coherence tomography, (170.2150) Endoscopic imaging, (170.3890) Medical optics instrumentation, (170.1610) Clinical applications     

A high-efficiency fiber-based imaging system for co-registered autofluorescence and optical coherence tomography

We present a power-efficient fiber-based imaging system capable of co-registered autofluorescence imaging and optical coherence tomography (AF/OCT). The system employs a custom fiber optic rotary joint (FORJ) with an embedded dichroic mirror to efficiently combine the OCT and AF pathways. This three-port wavelength multiplexing FORJ setup has a throughput of more than 83% for collected AF emission, significantly more efficient compared to previously reported fiber-based methods. A custom 900 µm diameter catheter ‒ consisting of a rotating lens assembly, double-clad fiber (DCF), and torque cable in a stationary plastic tube ‒ was fabricated to allow AF/OCT imaging of small airways in vivo. We demonstrate the performance of this system ex vivo in resected porcine airway specimens and in vivo in human on fingers, in the oral cavity, and in peripheral airways.OCIS codes: (110.0110) Imaging systems, (110.2350) Fiber optics imaging, (110.4500) Optical coherence tomography, (170.2520) Fluorescence microscopy, (170.3890) Medical optics instrumentation     

Bubble wrap for optical trapping and cell culturing

In this paper, we demonstrate that the bubbles of bubble wrap make ideal trapping chambers for integration with low-cost optical manipulation. The interior of the bubbles is sterile and gas permeable, allowing for the bubbles to be used to store and culture cells, while the flat side of the bubble wrap is of sufficient optical quality to allow for optical trapping inside the bubbles. Through the use of a 100 W bulb to cure hanging droplets of PDMS, a low-cost optical trapping system was constructed. Effector T cells were cultured in bubble wrap for 8 days and then trapped with the PDMS droplet based optical manipulation. These techniques further demonstrate the opportunities for biophysical analysis afforded through repurposing common materials in resource-limited settings.OCIS codes: (350.4855) Optical tweezers or optical manipulation, (140.7010) Laser trapping, (220.0220) Optical design and fabrication, (120.4610) Optical fabrication, (000.2170) Equipment and techniques, (180.0180) Microscopy     

Compact optical integration instrument to measure intraocular straylight

Optical measurement of straylight in the human eye is a challenging task. Issues such as illumination geometry, detector sensitivity and dynamic range as well as various inherent artifacts must be addressed. We developed a novel instrument based on the principle of double-pass optical integration adapted for fast measurements in a clinical setting. The experimental setup was validated using four different diffusers introduced in front of the eyes of ten subjects. Measurement limitations and future implications of rapid optical measurement of straylight in ophthalmic diagnosis are discussed.OCIS codes: (170.0170) Medical optics and biotechnology, (330.4460) Ophthalmic optics and devices, (290.2648) Stray light, (330.5370) Physiological optics     

Improved visualization of outer retinal morphology with aberration cancelling reflective optical design for adaptive optics - optical coherence tomography

We present an aberration cancelling optical design for a reflective adaptive optics - optical coherence tomography (AO-OCT) retinal imaging system. The optical performance of this instrument is compared to our previous multimodal AO-OCT/AO-SLO retinal imaging system. The feasibility of new instrumentation for improved visualization of microscopic retinal structures is discussed. Examples of images acquired with this new AO-OCT instrument are presented.OCIS codes: (110.4500) Optical coherence tomography, (010.1080) Active or adaptive optics, (220.1000) Aberration compensation, (170.0110) Imaging systems, (170.4470) Ophthalmology, (120.3890) Medical optics instrumentation     

Novel catheter enabling simultaneous radiofrequency ablation and optical coherence reflectometry

A novel radiofrequency ablation catheter has been developed with integrated custom designed optics, enabling real-time monitoring of radiofrequency ablation procedures through polarization-sensitive optical coherence reflectometry. The optics allow for proper tissue illumination through a view-port machined in the catheter tip, thus providing lesion depth control over the RF ablation treatment. The system was verified in an in-vitro model of swine myocardium. Optical performance and thermal stability was confirmed after more than 25 procedures, without any damage to the optical assembly induced by thermal stress or material degradation. The use of this catheter in RF ablation treatments may make possible to assess lesion depth during therapy, thus translating into a reduction of potential complications on the procedure.OCIS codes: (110.4500) Optical coherence tomography, (120.4570) Optical design of instruments, (170.1020) Ablation of tissue, (170.3890) Medical optics instrumentation     

Miniature,minimally invasive,tunable endoscope for investigation of the middle ear

We demonstrate a miniature, tunable, minimally invasive endoscope for diagnosis of the auditory system. The probe is designed to sharply image anatomical details of the middle ear without the need for physically adjusting the position of the distal end of the endoscope. This is achieved through the addition of an electrowetted, tunable, electronically-controlled lens to the optical train. Morphological imaging is enabled by scanning light emanating from an optical coherence tomography system. System performance was demonstrated by imaging part of the ossicular chain and wall of the middle ear cavity of a normal mouse. During the experiment, we electronically moved the plane of best focus from the incudo-stapedial joint to the stapedial artery. Repositioning the object plane allowed us to image anatomical details of the middle ear beyond the depth of field of a static optical system. We also demonstrated for the first time to our best knowledge, that an optical system with an electrowetted, tunable lens may be successfully employed to measure sound-induced vibrations within the auditory system by measuring the vibratory amplitude of the tympanic membrane in a normal mouse in response to pure tone stimuli.OCIS codes: (110.4500) Optical coherence tomography, (170.0170) Medical optics and biotechnology, (220.0220) Optical design and fabrication, (120.7280) Vibration analysis, (170.4580) Optical diagnostics for medicine, (170.4940) Otolaryngology, (170.2150) Endoscopic imaging     

Design considerations for polarization-sensitive optical coherence tomography with a single input polarization state

Using a generalized design for a polarization-sensitive optical coherence tomography (PS-OCT) system with a single input polarization state (SIPS), we prove the existence of an infinitely large design space over which it is possible to develop simple PS-OCT systems that yield closed form expressions for birefringence. Through simulation and experiment, we validate this analysis by demonstrating new configurations for PS-OCT systems, and present guidelines for the general design of such systems in light of their inherent inaccuracies. After accounting for systemic errors, alternative designs exhibit similar performance on average to the traditional SIPS PS-OCT system. This analysis could be extended to systems with multiple input polarization states and could usher in a new generation of PS-OCT systems optimally designed to probe specific birefringent samples with high accuracy.OCIS codes: (110.4500) Optical coherence tomography, (230.5440) Polarization-selective devices, (120.3890) Medical optics instrumentation     

Design of high-performance adaptive objective lens with large optical depth scanning range for ultrabroad near infrared microscopic imaging

We report on the theory and design of adaptive objective lens for ultra broadband near infrared light imaging with large dynamic optical depth scanning range by using an embedded tunable lens, which can find wide applications in deep tissue biomedical imaging systems, such as confocal microscope, optical coherence tomography (OCT), two-photon microscopy, etc., both in vivo and ex vivo. This design is based on, but not limited to, a home-made prototype of liquid-filled membrane lens with a clear aperture of 8mm and the thickness of 2.55mm ~3.18mm. It is beneficial to have an adaptive objective lens which allows an extended depth scanning range larger than the focal length zoom range, since this will keep the magnification of the whole system, numerical aperture (NA), field of view (FOV), and resolution more consistent. To achieve this goal, a systematic theory is presented, for the first time to our acknowledgment, by inserting the varifocal lens in between a front and a back solid lens group. The designed objective has a compact size (10mm-diameter and 15mm-length), ultrabroad working bandwidth (760nm - 920nm), a large depth scanning range (7.36mm in air) — 1.533 times of focal length zoom range (4.8mm in air), and a FOV around 1mm × 1mm. Diffraction-limited performance can be achieved within this ultrabroad bandwidth through all the scanning depth (the resolution is 2.22 μm - 2.81 μm, calculated at the wavelength of 800nm with the NA of 0.214 - 0.171). The chromatic focal shift value is within the depth of focus (field). The chromatic difference in distortion is nearly zero and the maximum distortion is less than 0.05%.OCIS codes: (220.0220) Optical design and fabrication, (220.1080) Active or adaptive optics, (080.2468) First-order optics, (080.2740) Geometric optical design, (170.3890) Medical optics instrumentation, (170.6900) Three-dimensional microscopy, (170.1790) Confocal microscopy, (170.4500) Optical coherence tomography