POF-yarn weaves: controlling the light out-coupling of wearable phototherapy devices.

Neonatal jaundice (hyperbilirubinaemia) is common in neonates and, often, intensive blue-light phototherapy is required to prevent long-term effects. A photonic textile can overcome three major incubator-related concerns: Insulation of the neonate, human contact, and usage restraints. This paper describes the development of a homogeneous luminous textile from polymer optical fibres to use as a wearable, long-term phototherapy device. The bend out-coupling of light from the POFs was related to the weave production, e.g. weave pattern and yarn densities. Comfort, determined by friction against a skin model and breathability, was investigated additionally. Our textile is the first example of phototherapeutic clothing that is produced sans post-processing allowing for faster commercial production.

Extended depth of focus intraocular lens: Chromatic performance.

We describe a first-and-second-diffractive-order intraocular lens ((1st,2nd)DIOL) within the class of hybrid refractive-diffractive designs for intraocular lenses (IOLs) and analyse its properties of focus extension and compensation of longitudinal chromatic aberration (LCA), particularly for lenses with low addition. Power, energy efficiency and their wavelength dependence are extended from monofocal IOL and conventional bifocal zeroth-and-first-diffractive-order IOL ((0th,1st)DIOL) to (1st,2nd)DIOL of low addition. Compensation of LCA is experimentally assessed in optical bench through the through-focus energy efficiency of three Tecnis IOLs with red, green and blue illuminations: ZA9003 (monofocal), ZKB00 (bifocal (0th,1st)DIOL with + 2.75 D add) and Symfony ZXR00. We prove Tecnis Symfony ZXR00 IOL can be considered an example of (1st,2nd)DIOL design of low addition, with LCA compensation in both the distance and intermediate foci, whereas the bifocal (0th,1st)DIOL does not compensate in the distance focus. However, the energy efficiency of (1st,2nd)DIOL for wavelengths other than the design wavelength is markedly more asymmetric.

Automated, highly reproducible, wide-field, light-based cortical mapping method using a commercial stereo microscope and its applications.

We introduce a more flexible optogenetics-based mapping system attached on a stereo microscope, which offers automatic light stimulation to individual regions of interest in the cortex that expresses light-activated channelrhodopsin-2 in vivo. Combining simultaneous recording of electromyography from specific forelimb muscles, we demonstrate that this system offers much better efficiency and precision in mapping distinct domains for controlling limb muscles in the mouse motor cortex. Furthermore, the compact and modular design of the system also yields a simple and flexible implementation to different commercial stereo microscopes, and thus could be widely used among laboratories.

Continuously zoom imaging probe for the multi-resolution foveated laparoscope.

In modern minimally invasive surgeries (MIS), standard laparoscopes suffer from the tradeoff between the spatial resolution and field of view (FOV). The inability of simultaneously acquiring high-resolution images for accurate operation and wide-angle overviews for situational awareness limits the efficiency and outcome of the MIS. A dual view multi-resolution foveated laparoscope (MRFL) which can simultaneously provide the surgeon with a high-resolution view as well as a wide-angle overview was proposed and demonstrated to have great potential for improving the MIS. Although experiment results demonstrated the high-magnification probe has an adequate magnification for viewing surgical details, the dual-view MRFL is limited to two fixed levels of magnifications. A fine adjustment of the magnification is highly desired for obtaining high resolution images with desired field coverage. In this paper, a high magnification probe with continuous zooming capability without any mechanical moving parts is demonstrated. By taking the advantages of two electrically tunable lenses, one for optical zoom and the other for image focus compensation, the optical magnification of the high-magnification probe varies from 2 × to 3 × compared with that of the wide-angle probe, while the focused object position stays the same as the wide-angle probe. The optical design and the tunable lens analysis are presented, followed by prototype demonstration.

Multimodal nonlinear endo-microscopy probe design for high resolution, label-free intraoperative imaging.

We present a portable, multimodal, nonlinear endo-microscopy probe designed for intraoperative oncological imaging. Application of a four-wave mixing noise suppression scheme using dual wavelength wave plates (DWW) and a polarization-maintaining fiber improves tissue signal collection efficiency, allowing for miniaturization. The probe, with a small 14 mm transversal diameter, includes a customized miniaturized two-axis MEMS (micro-electromechanical system) raster scanning mirror and micro-optics with an illumination laser delivered by a polarization-maintaining fiber. The probe can potentially be integrated into the arms of a surgical robot, such as da Vinci robotic surgery system, due to its minimal cross sectional area. It has the ability to incorporate multiple imaging modalities including CARS (coherent anti-Stokes Raman scattering), SHG (second harmonic generation), and TPEF (two-photon excited fluorescence) in order to allow the surgeon to locate tumor cells within the context of normal stromal tissue. The resolution of the endo-microscope is experimentally determined to be 0.78 µm, a high level of accuracy for such a compact probe setup. The expected resolution of the as-built multimodal, nonlinear, endo-microscopy probe is 1 µm based on the calculation tolerance allocation using Monte-Carlo simulation. The reported probe is intended for use in laparoscopic or radical prostatectomy, including detection of tumor margins and avoidance of nerve impairment during surgery.

Modal demultiplexing properties of tapered and nanostructured optical fibers for in vivo optogenetic control of neural activity.

Optogenetic approaches to manipulate neural activity have revolutionized the ability of neuroscientists to uncover the functional connectivity underlying brain function. At the same time, the increasing complexity of in vivo optogenetic experiments has increased the demand for new techniques to precisely deliver light into the brain, in particular to illuminate selected portions of the neural tissue. Tapered and nanopatterned gold-coated optical fibers were recently proposed as minimally invasive multipoint light delivery devices, allowing for site-selective optogenetic stimulation in the mammalian brain [Pisanello , Neuron82, 1245 (2014)]. Here we demonstrate that the working principle behind these devices is based on the mode-selective photonic properties of the fiber taper. Using analytical and ray tracing models we model the finite conductance of the metal coating, and show that single or multiple optical windows located at specific taper sections can outcouple only specific subsets of guided modes injected into the fiber.

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.

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.

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%.

Characterization and in-vivo evaluation of a multi-resolution foveated laparoscope for minimally invasive surgery.

The state-of-the-art laparoscope lacks the ability to capture high-magnification and wide-angle images simultaneously, which introduces challenges when both close- up views for details and wide-angle overviews for orientation are required in clinical practice. A multi-resolution foveated laparoscope (MRFL) which can provide the surgeon both high-magnification close-up and wide-angle images was proposed to address the limitations of the state-of-art surgical laparoscopes. In this paper, we present the overall system design from both clinical and optical system perspectives along with a set of experiments to characterize the optical performances of our prototype system and describe our preliminary in-vivo evaluation of the prototype with a pig model. The experimental results demonstrate that at the optimum working distance of 120mm, the high-magnification probe has a resolution of 6.35lp/mm and image a surgical area of 53 × 40mm(2); the wide-angle probe provides a surgical area coverage of 160 × 120mm(2) with a resolution of 2.83lp/mm. The in-vivo evaluation demonstrates that MRFL has great potential in clinical applications for improving the safety and efficiency of the laparoscopic surgery.

Optical design and evaluation of a 4 mm cost-effective ultra-high-definition arthroscope.

High definition and magnification rigid endoscope plays an important role in modern minimally invasive medical surgery and diagnosis. In this paper, we present the design and evaluation methods of a high definition rigid endoscope, specifically an arthroscope, with a large depth of field (DOF). The incident heights and exit angles of the sampled rays on the relay lens are controlled during the optimization process to ensure an effective field view (70°) and a normal ray path within the limited lens diameter of 2.7 mm. The lens is set up as a multi-configuration system with two extreme and one middle object distances to cover a large DOF. As a result, an entrance pupil of 0.3 mm is achieved for the first time, to bring the theoretical resolution to 23.1 lps/mm in the object space at a working distance of 20 mm, with the wavelength of 0.532 um. The modulation transfer function (MTF) curves approach diffraction limit, and the values are all higher than 0.3 at 160 line pairs/mm (lps/mm) in the image space. Meanwhile, stray light caused by total internal reflection on the inner wall of the rod lenses and the objective lens is eliminated. The measured resolution in the object space at a 20 mm working distance is 22.3 lps/mm, and test results show that other performance characteristics also fulfill design requirements. The relay lenses are designed with only one type of the spacer and two types of lenses to greatly reduce the fabrication and assembly cost. The design method has important research and application values for lens systems used in modern minimally invasive medical surgery and industrial non-destructive testing area.

Integrated fluorescence correlation spectroscopy device for point-of-care clinical applications.

We describe an optical system which reduces the cost and complexity of fluorescence correlation spectroscopy (FCS), intended to increase the suitability of the technique for clinical use. Integration of the focusing optics and sample chamber into a plastic component produces a design which is simple to align and operate. We validate the system by measurements on fluorescent dye, and compare the results to a commercial instrument. In addition, we demonstrate its application to measurements of concentration and multimerization of the clinically relevant protein von Willebrand factor (vWF) in human plasma.

Achromatized endomicroscope objective for optical biopsy.

Currently, researchers and clinicians lack achromatized endomicroscope objectives that are as narrow as biopsy needles. We present a proof-of-concept prototype that validates the optical design of an NA0.4 objective. The objective, built with plastic lenses, has a 0.9 mm clear aperture and is achromatized from 452 nm to 623 nm. The objective's measured Strehl ratio is 0.74 ± 0.05 across a 250 µm FOV. We perform optical sectioning via structured illumination through the objective while capturing fluorescence images of breast carcinoma cells stained with proflavine and cresyl violet. This technology has the potential to improve optical biopsies and provide the next step forward in cancer diagnostics.

Introduction to the BODA 2013 feature issue.

The guest editors introduce a feature issue containing papers based on research presented at the BODA 2013 meeting.

Scanning thin-sheet laser imaging microscopy (sTSLIM) with structured illumination and HiLo background rejection.

We report replacement of one side of a static illumination, dual sided, thin-sheet laser imaging microscope (TSLIM) with an intensity modulated laser scanner in order to implement structured illumination (SI) and HiLo image demodulation techniques for background rejection. The new system is equipped with one static and one scanned light-sheet and is called a scanning thin-sheet laser imaging microscope (sTSLIM). It is an optimized version of a light-sheet fluorescent microscope that is designed to image large specimens (<15 mm in diameter). In this paper we describe the hardware and software modifications to TSLIM that allow for static and uniform light-sheet illumination with SI and HiLo image demodulation. The static light-sheet has a thickness of 3.2 µm; whereas, the scanned side has a light-sheet thickness of 4.2 µm. The scanned side images specimens with subcellular resolution (<1 µm lateral and <4 µm axial resolution) with a size up to 15 mm. SI and HiLo produce superior contrast compared to both the uniform static and scanned light-sheets. HiLo contrast was greater than SI and is faster and more robust than SI because as it produces images in two-thirds of the time and exhibits fewer intensity streaking artifacts.