Novel optical fiber Vernier immunosensor based on cascading Sagnac loops embedded with excessively tilted fiber grating for specific detection of canine distemper virus

A novel optical fiber Vernier effect (VE) biosensor based on cascading Sagnac loops embedded with excessively tilted fiber grating (ExTFG) is proposed for the label free and specific detection of canine distemper virus (CDV). The VE was realized by cascading two different Sagnac loops with similar free spectrum range (FSR), one of which was integrated with panda-type polarization maintaining fiber (PMF) as the reference loop, and the other was embedded with ExTFG as the sensing loop. Owning to the amplified function of the VE, the refractive index (RI) sensitivity of the proposed sensing structure reached −1914.89 nm/RIU, which is approximately 12 times higher than that of the single ExTFG based RI sensor. Furthermore, the ExTFG in sensing loop was modified by graphene oxide (GO) and bio-functionalized by the CDV monoclonal antibodies (anti-CDV MAbs) for the specific detection of the CDV. Experimental results show that the proposed optical fiber Vernier sensor could detect the CDV in buffer solution with concentration as low as 1 pg/mL, and the sensitivity was about −1.18 nm/[log(mg/ml)] in the concentration range of 1 pg/mL ~ 50 ng/mL. The excellent specific and clinical properties of the biosensor were verified by immunoassays for fetal bovine serum, Toxoplasma gondii, rabies virus and CDV serum in sequence. Due to the sensitivity amplification function of VE, dense comb spectrum of the Sagnac loop and the stable interference spectra maintained by the polarized light, the proposed biosensor possesses the combined advantages of high sensitivity, high Q-factor and high stability, which may have potential applications in biosensing fields.     

A new deep learning method for image deblurring in optical microscopic systems

Deconvolution is the most commonly used image processing method in optical imaging systems to remove the blur caused by the point‐spread function (PSF). While this method has been successful in deblurring, it suffers from several disadvantages, such as slow processing time due to multiple iterations required to deblur and suboptimal in cases where the experimental operator chosen to represent PSF is not optimal. In this paper, we present a deep‐learning‐based deblurring method that is fast and applicable to optical microscopic imaging systems. We tested the robustness of proposed deblurring method on the publicly available data, simulated data and experimental data (including 2D optical microscopic data and 3D photoacoustic microscopic data), which all showed much improved deblurred results compared to deconvolution. We compared our results against several existing deconvolution methods. Our results are better than conventional techniques and do not require multiple iterations or pre‐determined experimental operator. Our method has several advantages including simple operation, short time to compute, good deblur results and wide application in all types of optical microscopic imaging systems. The deep learning approach opens up a new path for deblurring and can be applied in various biomedical imaging fields.     

基于纳米酶的比色生物传感器在生物医学检测中的应用

比色生物传感技术由于具有灵敏度高、方法简单并且容易操作等优点，已广泛应用于生物环境中污染物检测、生物体内重要标志物的检测以及癌症筛查等多个领域。基于纳米酶的比色生物传感器主要是借助纳米酶自身所具有的催化能力，模拟类过氧化物酶活性，将显色剂氧化生成有色溶液，从而实现可视化检测，并通过对有色溶液吸光度的检测得到相关物质的含量。与无纳米酶的比色生物传感器相比，基于纳米酶的比色生物传感器具有选择性更高、检测更快以及灵敏度更高等优点。纳米酶在具有天然酶活性的同时还具有成本低、稳定性好的、易于合成等优点，其相关研究越来越广泛。目前，基于纳米酶的比色生物传感器已成为辅助相关医学检测的重要方法，同时也广泛应用于便携和实时性相关检测当中，为医学检测提供了重要的支持和保障。为了提高比色生物传感器的灵敏度以及应用范围，研究人员也在致力于增加可检测物质的种类以及纳米酶种类的多样化等。本文主要介绍基于纳米酶的比色生物传感器的检测原理、几类典型的纳米酶，以及基于纳米酶的比色生物传感器在生物医学检测领域中的应用情况和研究进展。     

Interferometric optical fiber sensor for optoacoustic endomicroscopy

Optical fiber sensors can offer robust and miniaturized detection of wideband ultrasound, yielding high sensitivity and immunity to electromagnetic interference. However, the lack of cost-effective manufacturing methods prevents the disseminated use of these sensors in biomedical applications. In this study, we developed and optimized a simple method to create optical cavities with high-quality mirrors for acoustic sensing based on micro-manipulation of UV-curable optical adhesives and electroless chemical silver deposition. This approach enables the manufacturing of ultrasound sensors based on Fabry-Pérot interferometers on optical fiber tips with minimal production costs. Characterization and high-resolution optoacoustic imaging experiments show that the manufacturing process yielded a fiber sensor with a small NEP () over a broad detection bandwidth (25 MHz), generally outperforming conventional piezoelectric based transducers. We discuss how the new manufacturing process leads to a high-performance acoustic detector that, due to low cost, can be used as a disposable sensor.     

Concept of photonic hook scalpel generated by shaped fiber tip with asymmetric radiation

Structured light have made deep impacts on modern biotechnology and clinical practice, with numerous optical systems and lasers currently being used in medicine to treat disease. We demonstrate a new concept of fiber-based optical hook scalpel. The subwavelength photonic hook is obtained in the vicinity of a shaped fiber tip with asymmetric radiation. A 1550 nm continuous-wave source, commonly used for medical imaging, has been required. Photonic hook with a lateral feature size less than the half-wavelength is achieved using a hemispherical shaped fiber tip with metallic mask. This breakthrough is carried out in ambient air by using a 4-μm-diameter fiber with a shaped tip. A good correlation is observed between the computed intensity distribution of photonic hook and the tip sizes. Photonic hook generated with a shaped fiber tip, easier to manipulate, shows far-reaching benefits for potential applications such as ophthalmic laser surgery, super-resolution microscopy, photolithography and material processing.     

Depth-dependent in vivo human skin backscattering spectra extraction from full-field optical coherence tomography

With homemade active crystalline fibers, we generated bright and broadband light sources for full-field optical coherence tomography, offering deep penetration into skin tissues with cellular resolution at a high frame rate. Extraction of backscattered spectra from the tissue has potential applications in biomedicine. The hysteresis nonlinearity of the piezoelectric transducer actuating the Mirau interferometer has been greatly reduced by a feedforward compensation approach. The linearized hysteresis response enables us to extract depth-dependent spectra accurately. To validate, the complex dispersion of a fused silica plate was characterized with 2% error. Further validation on an in vitro setting, the backscattered spectra from indocyanine green pigment and nonpigmented microspheres were obtained and verified. For in vivo skin measurement, the backscattered spectra show depth-dependent spectral shift and bandwidth variation due to the complex skin anatomy and pigment absorption. Such a high-speed spectra acquisition of in vivo deep tissue backscattering could lead to disease diagnosis in clinical settings.     

Highly-sensitive organophosphorous pesticide biosensors based on nanostructured films of acetylcholinesterase and CdTe quantum dots

The optical transducer of CdTe semiconductor quantum dots (QDs) has been integrated with acetylcholinesterase enzyme (AChE) by the layer-by-layer (LbL) assembly technique, resulting in a highly sensitive biosensor for detection of organophosphorus pesticides (OPs) in vegetables and fruits based on enzyme inhibition mechanism. The detection limits of the proposed biosensors are as low as 1.05 × 10(-11) M for paraoxon and 4.47 × 10(-12) M for parathion, which are significantly better than those of the conventional GC/MS methods or amperometric biosensors (0.5 nM). These biosensors are used for quick determination of low concentrations of OPs in real vegetable and fruit samples and exhibit satisfactory reproducibility and accuracy. Moreover, the stock stability of the biosensors are very good due to the stabilizing environment for the enzyme in the nanostructures made by LbL technique. Many advantages provided by these biosensors, like fluorescent change recognized by naked eyes and mass production with low cost, will facilitate future development of rapid and high-throughput screening of OPs.     

Enhanced efficiency of a capillary-based biosensor over an optical fiber biosensor for detecting calpastatin

A capillary-based optical biosensor has been developed to detect calpastatin, an indicator of meat tenderness. Longissimus muscle samples (n = 11) were extracted from beef carcasses at 0 and 48 h post-mortem. These samples were assayed for calpastatin by traditional laboratory methods and with a newly developed capillary tube biosensor as well as for Warner–Bratzler shear force (WBSF) and crude protein and the responses were compared. Additionally, the response from the capillary-based biosensor was compared to a previously developed optical fiber biosensor. When the 0 and 48 h sampling periods were combined, the capillary tube biosensor was moderately accurate in predicting calpastatin activity (R² = 0.6058). There was less variation in the 0 h capillary tube biosensor compared to the 0 h pre-column (P = 0.006) and post-column optical fiber biosensors (P = 0.047), therefore the capillary tube biosensor is a more precise system of measurement. This research further advances the development of a calpastatin biosensor and makes online assessment one step closer to reality.     

Optical fan for single‐cell screening

The single‐cell screening has attracted great attentions in advanced biomedicine and tissue biology, especially for the early disease diagnosis and treatment monitoring. In this work, by using a specific‐designed fiber probe with a flat facet, we propose an “optical fan” strategy to screen K562 cells at the single‐cell level from a populations of RBCs. After the 980‐nm laser beam injected into the fiber probe, the RBCs were blown away but holding target K562 cells in place. Further, multiple leukemic cells can be screened from hundreds of red blood cells, providing an efficient approach for the cell screening. The experimental results were interpreted by the numerical simulation, and the stiffness of optical fan was also discussed.     

High resolution,label‐free photoacoustic imaging of live chicken embryo developing in bioengineered eggshell

Chicken embryos have been proven to be an attractive vertebrate model for biomedical research. They have helped in making significant contributions for advancements in various fields like developmental biology, cancer research and cardiovascular studies. However, a non‐invasive, label‐free method of imaging live chicken embryo at high resolution still needs to be developed and optimized. In this work, we have shown the potential of photoacoustic tomography (PAT) for imaging live chicken embryos cultured in bioengineered eggshells. Laser pulses at wavelengths of 532 and 740 nm were used for attaining cross‐sectional images of chicken embryos at different developmental stages. Cross‐sections along different depths were imaged to gain knowledge of the relative depth of different vessels and organs. Due to high optical absorption of vasculature and embryonic eye, images with good optical contrast could be acquired using this method. We have thus reported a label‐free method of performing cross‐sectional imaging of chicken embryos at high resolution demonstrating the capacity of PAT as a promising tool for avian embryo imaging.     

Low-power compact continuous-wave stimulated emission depletion microscopy

Stimulated emission depletion (STED) microscopy can break the optical diffraction barrier and provide subdiffraction resolution. According to the STED superresolution imaging principle, the resolution of STED is positively related to the power of the depletion laser. However, high-laser power largely limits the study of living cells or living bodies. Moreover, the high complexity and high cost of conventional pulsed STED microscopy limit the application of this technique. Therefore, this paper describes a simple continuous-wave STED (CW-STED) system constructed on a 45 × 60 cm breadboard and combined with digitally enhanced (DE) technology; low-power superresolution imaging is realized, which has the advantages of reducing system complexity and cost. The low-system complexity, low cost, and low-power superresolution imaging features of CW-STED have great potential to advance the application of STED microscopy in biological research.     

Dual‐ and single‐shot susceptibility ratio measurements with circular polarizations in second‐harmonic generation microscopy

Polarization‐resolved second‐harmonic generation (P‐SHG) microscopy is a technique capable of characterizing nonlinear optical properties of noncentrosymmetric biomaterials by extracting the nonlinear susceptibility tensor components ratio , with z‐axis parallel and x‐axis perpendicular to the C₆ symmetry axis of molecular fiber, such as a myofibril or a collagen fiber. In this paper, we present two P‐SHG techniques based on incoming and outgoing circular polarization states for a fast extraction of : A dual‐shot configuration where the SHG circular anisotropy generated using incident right‐ and left‐handed circularly‐polarized light is measured; and a single‐shot configuration for which the SHG circular anisotropy is measured using only one incident circular polarization state. These techniques are used to extract the of myosin fibrils in the body wall muscles of Drosophila melanogaster larva. The results are in good agreement with values obtained from the double Stokes‐Mueller polarimetry. The dual‐ and single‐shot circular anisotropy measurements can be used for fast imaging that is independent of the in‐plane orientation of the sample. They can be used for imaging of contracting muscles, or for high throughput imaging of large sample areas.     

Optical‐resolution photoacoustic microscopy with ultrafast dual‐wavelength excitation

Fast functional and molecular photoacoustic microscopy requires pulsed laser excitations at multiple wavelengths with enough pulse energy and short wavelength‐switching time. Recent development of stimulated Raman scattering in optical fiber offers a low‐cost laser source for multiwavelength photoacoustic imaging. In this approach, long fibers temporally separate different wavelengths via optical delay. The time delay between adjacent wavelengths may eventually limits the highest A‐line rate. In addition, a long‐time delay in fiber may limit the highest pulse energy, leading to poor image quality. In order to achieve high pulse energy and ultrafast dual‐wavelength excitation, we present optical‐resolution photoacoustic microscopy with ultrafast dual‐wavelength excitation and a signal separation method. The signal separation method is validated in numerical simulation and phantom experiments. We show that when two photoacoustic signals are partially overlapped with a 50‐ns delay, they can be recovered with 98% accuracy. We apply this ultrafast dual‐wavelength excitation technique to in vivo OR‐PAM. Results demonstrate that A‐lines at two wavelengths can be successfully separated, and sO₂ values can be reliably computed from the separated data. The ultrafast dual‐wavelength excitation enables fast functional photoacoustic microscopy with negligible misalignment among different wavelengths and high pulse energy, which is important for in vivo imaging of microvascular dynamics.     

Bio‐analytical applications of microbial fuel cell–based biosensors for onsite water quality monitoring

Globally, sustainable provision of high‐quality safe water is a major challenge of the 21st century. Various chemical and biological monitoring analytics are presently utilized to guarantee the availability of high‐quality water. However, these techniques still face some challenges including high costs, complex design and onsite and online limitations. The recent technology of using microbial fuel cell (MFC)‐based biosensors holds outstanding potential for the rapid and real‐time monitoring of water source quality. MFCs have the advantages of simplicity in design and efficiency for onsite sensing. Even though some sensing applications of MFCs were previously studied, e.g. biochemical oxygen demand sensor, recently numerous research groups around the world have presented new practical applications of this technique, which combine multidisciplinary scientific knowledge in materials science, microbiology and electrochemistry fields. This review presents the most updated research on the utilization of MFCs as potential biosensors for monitoring water quality and considers the range of potentially toxic analytes that have so far been detected using this methodology. The advantages of MFCs over established technology are also considered as well as future work required to establish their routine use.     

An optical system for noninvasive microscopy of psoriatic mice in vivo

Psoriasis is a chronic inflammatory skin disease involved with both complex morphological changes of skin and immune processes. The clinical diagnostics and research of psoriasis often require invasive biopsy which lacks their real-time dynamics in vivo. Here we report a noninvasive microscopic system developed by combining in vivo fluorescent microscopy, optical clearing, and immunolabeling to enable real-time imaging of immune cells and cytokines in blood flow in psoriatic animal models. The vascular morphology and time-lapse kinetics of interleukin (IL)-23, IL-17, tumor necrosis factor-α, and CD4+ cells in blood are captured at submicron resolution through the thickening epidermis and opaque scales during the development of psoriasis in vivo. Our data suggest IL-23 recruits CD4+ cells to release IL-17 in blood that further leaks out in the psoriatic skin area. This optical system enables noninvasive and real-time assessment of immune molecules and cells in vivo, providing good potential for medical researches on psoriasis.     

Development of hyperthermia measurable fiber radiometric thermometer for thermotherapy

Temperature monitoring is extremely important during thermotherapy. Fiber‐optic temperature sensors are preferred because of their flexibility and immunity to electromagnetic interference. Although many types of fiber‐optic sensors have been developed, clinically adopting them remains challenging. Here, we report a silica fiber‐based radiometric thermometer using a low‐cost extended InGaAs detector to detect black body radiation between 1.7 and 2.4 μm. For the first time, this silica fiber‐based thermometer is capable of measuring temperatures down to 35°C, making it suitable for monitoring hyperthermia during surgery. In particular, the thermometer has potential for seamless integration with current silica fiber catheters, which are widely used in laser interstitial thermotherapy. The feasibility, capability and sensitivity of tracking tissue temperature variation were proved through ex vivo tissue studies. After further improvement, the technology has the potential to be translated into clinics for monitoring tissue temperature.     

Progress of new label-free techniques for biosensors: a review

The detection techniques used in biosensors can be broadly classified into label-based and label-free. Label-based detection relies on the specific properties of labels for detecting a particular target. In contrast, label-free detection is suitable for the target molecules that are not labeled or the screening of analytes which are not easy to tag. Also, more types of label-free biosensors have emerged with developments in biotechnology. The latest developed techniques in label-free biosensors, such as field-effect transistors-based biosensors including carbon nanotube field-effect transistor biosensors, graphene field-effect transistor biosensors and silicon nanowire field-effect transistor biosensors, magnetoelastic biosensors, optical-based biosensors, surface stress-based biosensors and other type of biosensors based on the nanotechnology are discussed. The sensing principles, configurations, sensing performance, applications, advantages and restriction of different label-free based biosensors are considered and discussed in this review. Most concepts included in this survey could certainly be applied to the development of this kind of biosensor in the future.     

Implantable self‐aligning fiber‐optic optomechanical devices for in vivo intraocular pressure‐sensing in artificial cornea

Artificial cornea is an effective treatment of corneal blindness. Yet, intraocular pressure (IOP) measurements for glaucoma monitoring remain an urgent unmet need. Here, we present the integration of a fiber‐optic Fabry‐Perot pressure sensor with an FDA‐approved keratoprosthesis for real‐time IOP measurements using a novel strategy based on optical‐path self‐alignment with micromagnets. Additionally, an alternative noncontact sensor‐interrogation approach is demonstrated using a bench‐top optical coherence tomography system. We show stable pressure readings with low baseline drift (<2.8 mm Hg) for >4.5 years in vitro and efficacy in IOP interrogation in vivo using fiber‐optic self‐alignment, with good initial agreement with the actual IOP. Subsequently, IOP drift in vivo was due to retroprosthetic membrane (RPM) formation on the sensor secondary to surgical inflammation (more severe in the current pro‐fibrotic rabbit model). This study paves the way for clinical adaptation of optical pressure sensors with ocular implants, highlighting the importance of controlling RPM in clinical adaptation.     

Miniaturized all fiber probe for optical coherence tomography and pH detection of biological tissue

We present a novel all-fiber probe with 710-μm outside diameter for combined optical coherence tomography and pH detection. In cancer surgery, a significant challenge is how to completely remove the malignant tumor without cutting too much normal tissue. The difference between cancer tissue and normal tissue not only lies in morphology and structure but also in tissue pH, where malignant tissue has a lower pH. This dual-modality probe combined optical coherence tomography and pH detection of biological tissue, is expected to determine whether the tissue is cancerous quickly and accurately. The probe utilizes a typical three-segment structure (double-clad fiber - no-core fiber - graded-index fiber). We obtained a lateral resolution of ~10.6 μm, a working distance of ~506 μm and a pH measurement accuracy of 0.01 pH unit for the probe. The performance of the all-fiber probe was verified through an ex vivo experiment using the porcine brain specimen.     

Superficial photothermal laser ablation of ex vivo sheep esophagus using a cone‐shaped optical fiber tip

Superficial photothermal laser ablation (SPLA) may be useful as a therapeutic approach producing a depth of injury that is sufficient to eliminate mucosal lesion but not deep enough to induce thermal effects in deeper tissue layers. The purpose of this preliminary study is twofold: (a) to describe design steps of a fiber probe capable of delivering a tightly focused laser beam, including Monte‐Carlo‐based simulations, and (b) to complete the initial testing of the probe in a sheep esophagus model, ex vivo. The cone‐shaped (tapered) fiber tip was obtained by chemical etching of the optical fiber. A 1505 nm diode laser providing power up to 500 mW was operated in continuous wave. The successful SPLA of the sheep mucosa layer was demonstrated for various speed‐power combinations, including 300 mW laser power at a surface scanning rate of 0.5 mm/s and 450 mW laser power at a surface scanning rate of 2.0 mm/s. Upon further development, this probe may be useful for endoscopic photothermal laser ablation of the mucosa layer using relatively low laser power.