Complex Spatial Illumination Scheme Optimization of Backscattering Mueller Matrix Polarimetry for Tissue Imaging and Biosensing.

Polarization imaging and sensing techniques have shown great potential for biomedical and clinical applications. As a novel optical biosensing technology, Mueller matrix polarimetry can provide abundant microstructural information of tissue samples. However, polarimetric aberrations, which lead to inaccurate characterization of polarization properties, can be induced by uneven biomedical sample surfaces while measuring Mueller matrices with complex spatial illuminations. In this study, we analyze the detailed features of complex spatial illumination-induced aberrations by measuring the backscattering Mueller matrices of experimental phantom and tissue samples. We obtain the aberrations under different spatial illumination schemes in Mueller matrix imaging. Furthermore, we give the corresponding suggestions for selecting appropriate illumination schemes to extract specific polarization properties, and then provide strategies to alleviate polarimetric aberrations by adjusting the incident and detection angles in Mueller matrix imaging. The optimized scheme gives critical criteria for the spatial illumination scheme selection of non-collinear backscattering Mueller matrix measurements, which can be helpful for the further development of quantitative tissue polarimetric imaging and biosensing.

Microsurgery Robots: Applications, Design, and Development.

Microsurgical techniques have been widely utilized in various surgical specialties, such as ophthalmology, neurosurgery, and otolaryngology, which require intricate and precise surgical tool manipulation on a small scale. In microsurgery, operations on delicate vessels or tissues require high standards in surgeons' skills. This exceptionally high requirement in skills leads to a steep learning curve and lengthy training before the surgeons can perform microsurgical procedures with quality outcomes. The microsurgery robot (MSR), which can improve surgeons' operation skills through various functions, has received extensive research attention in the past three decades. There have been many review papers summarizing the research on MSR for specific surgical specialties. However, an in-depth review of the relevant technologies used in MSR systems is limited in the literature. This review details the technical challenges in microsurgery, and systematically summarizes the key technologies in MSR with a developmental perspective from the basic structural mechanism design, to the perception and human-machine interaction methods, and further to the ability in achieving a certain level of autonomy. By presenting and comparing the methods and technologies in this cutting-edge research, this paper aims to provide readers with a comprehensive understanding of the current state of MSR research and identify potential directions for future development in MSR.

Nanostructured organic photosensitizer aggregates in disease phototheranostics.

Aggregate science provides promising opportunities for the discovery of novel disease phototheranostics. Under the guidance of aggregology and the Jablonski energy level diagram, photosensitizer aggregates with tunable photophysical properties can consequently result in tailorable diagnosis and treatment modalities. This review summarizes recent advances in the formation of nanostructured organic photosensitizer aggregates, their photophysical processes (e.g., radiative emission, vibrational relaxation, and intersystem crossing), and particularly, their applications in disease phototheranostics such as fluorescence imaging and sensing, photothermal therapy, photoacoustic imaging, and photodynamic therapy. It is expected that this comprehensive summary will provide guidance for the construction of nanostructured organic photosensitizer aggregates, for establishment of aggregation-photophysical property relationships and the development of novel disease phototheranostic nanomedicines.

Quantum sensors for biomedical applications.

Quantum sensors are finding their way from laboratories to the real world, as witnessed by the increasing number of start-ups in this field. The atomic length scale of quantum sensors and their coherence properties enable unprecedented spatial resolution and sensitivity. Biomedical applications could benefit from these quantum technologies, but it is often difficult to evaluate the potential impact of the techniques. This Review sheds light on these questions, presenting the status of quantum sensing applications and discussing their path towards commercialization. The focus is on two promising quantum sensing platforms: optically pumped atomic magnetometers, and nitrogen-vacancy centres in diamond. The broad spectrum of biomedical applications is highlighted by four case studies ranging from brain imaging to single-cell spectroscopy.

GRGB rPPG: An Efficient Low-Complexity Remote Photoplethysmography-Based Algorithm for Heart Rate Estimation.

Remote photoplethysmography (rPPG) is a promising contactless technology that uses videos of faces to extract health parameters, such as heart rate. Several methods for transforming red, green, and blue (RGB) video signals into rPPG signals have been introduced in the existing literature. The RGB signals represent variations in the reflected luminance from the skin surface of an individual over a given period of time. These methods attempt to find the best combination of color channels to reconstruct an rPPG signal. Usually, rPPG methods use a combination of prepossessed color channels to convert the three RGB signals to one rPPG signal that is most influenced by blood volume changes. This study examined simple yet effective methods to convert the RGB to rPPG, relying only on RGB signals without applying complex mathematical models or machine learning algorithms. A new method, GRGB rPPG, was proposed that outperformed most machine-learning-based rPPG methods and was robust to indoor lighting and participant motion. Moreover, the proposed method estimated the heart rate better than well-established rPPG methods. This paper also discusses the results and provides recommendations for further research.

Fast histological assessment of adipose tissue inflammation by label-free mid-infrared optoacoustic microscopy.

Conventional histology, as well as immunohistochemistry or immunofluorescence, enables the study of morphological and phenotypical changes during tissue inflammation with single-cell accuracy. However, although highly specific, such techniques require multiple time-consuming steps to apply exogenous labels, which might result in morphological deviations from native tissue structures. Unlike these techniques, mid-infrared (mid-IR) microspectroscopy is a label-free optical imaging method that retrieves endogenous biomolecular contrast without altering the native composition of the samples. Nevertheless, due to the strong optical absorption of water in biological tissues, conventional mid-IR microspectroscopy has been limited to dried thin (5-10 µm) tissue preparations and, thus, it also requires time-consuming steps-comparable to conventional imaging techniques. Here, as a step towards label-free analytical histology of unprocessed tissues, we applied mid-IR optoacoustic microscopy (MiROM) to retrieve intrinsic molecular contrast by vibrational excitation and, simultaneously, to overcome water-tissue opacity of conventional mid-IR imaging in thick (mm range) tissues. In this proof-of-concept study, we demonstrated application of MiROM for the fast, label-free, non-destructive assessment of the hallmarks of inflammation in excised white adipose tissue; i.e., formation of crown-like structures and changes in adipocyte morphology.

Effectiveness of Remote PPG Construction Methods: A Preliminary Analysis.

The contactless recording of a photoplethysmography (PPG) signal with a Red-Green-Blue (RGB) camera is known as remote photoplethysmography (rPPG). Studies have reported on the positive impact of using this technique, particularly in heart rate estimation, which has led to increased research on this topic among scientists. Therefore, converting from RGB signals to constructing an rPPG signal is an important step. Eight rPPG methods (plant-orthogonal-to-skin (POS), local group invariance (LGI), the chrominance-based method (CHROM), orthogonal matrix image transformation (OMIT), GREEN, independent component analysis (ICA), principal component analysis (PCA), and blood volume pulse (PBV) methods) were assessed using dynamic time warping, power spectrum analysis, and Pearson's correlation coefficient, with different activities (at rest, during exercising in the gym, during talking, and while head rotating) and four regions of interest (ROI): the forehead, the left cheek, the right cheek, and a combination of all three ROIs. The best performing rPPG methods in all categories were the POS, LGI, and OMI methods; each performed well in all activities. Recommendations for future work are provided.

Surface-enhanced Raman scattering: An emerging tool for sensing cellular function.

Continuous long-term intracellular imaging and multiplexed monitoring of biomolecular changes associated with key cellular processes remains a challenge for the scientific community. Recently, surface-enhanced Raman scattering (SERS) has been demonstrated as a powerful spectroscopic tool in the field of biology owing to its significant advantages. Some of these include the ability to provide molecule-specific information with exquisite sensitivity, working with small volumes of precious samples, real-time monitoring, and optimal optical contrast. More importantly, the availability of a large number of novel Raman reporters with narrower full width at half maximum (FWHM) of spectral peaks/vibrational modes than conventional fluorophores has created a versatile palette of SERS-based probes that allow targeted multiplex sensing surpassing the detection sensitivity of even fluorescent probes. Due to its nondestructive nature, its applicability has been recognized for biological sensing, molecular imaging, and dynamic monitoring of complex intracellular processes. We critically discuss recent developments in this area with a focus on different applications where SERS has been used for obtaining information that remains elusive for conventional imaging methods. Current reports indicate that SERS has made significant inroads in the field of biology and has the potential to be used for in vivo human applications. This article is categorized under: Diagnostic Tools > In Vitro Nanoparticle-Based Sensing Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Diagnostic Tools > Biosensing Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.

Fourier-Transform-Based Surface Measurement and Reconstruction of Human Face Using the Projection of Monochromatic Structured Light.

This work presents a new approach of surface measurement of human face via the combination of the projection of monochromatic structured light, the optical filtering technique, the polarization technique and the Fourier-transform-based image-processing algorithm. The theoretical analyses and experimental results carried out in this study showed that the monochromatic feature of projected fringe pattern generated using our designed laser-beam-based optical system ensures the use of optical filtering technique for removing the effect of background illumination; the linearly-polarized characteristic makes it possible to employ a polarizer for eliminating the noised signal contributed by multiply-scattered photons; and the high-contrast sinusoidal fringes of the projected structured light provide the condition for accurate reconstruction using one-shot measurement based on Fourier transform profilometry. The proposed method with the portable and stable optical setup may have potential applications of indoor medical scan of human face and outdoor facial recognition without strict requirements of a dark environment and a stable object being observed.

Near-infrared temperature-switchable fluorescence nanoparticles.

BACKGROUND: Near infrared (NIR) environment-sensitive fluorophores are highly desired for many biomedical applications because of its non-invasive operation, high sensitivity and specificity, non-ionizing radiation and deep penetration in biological tissue. When the fluorophores are appropriately encapsulated in or conjugated with some thermal-sensitive polymers, they could work as excellent temperature-sensing probes. METHODS: In this study, we synthesized and characterized a series of NIR temperature-switchable nanoparticles based on two series of NIR fluorophores aza-BODIPY (ADP is used for abbreviation in this work) and Zinc phthalocyanine (ZnPc) and four pluronic polymers (F127, F98, F68 and F38). Encapsulating the fluorophores in the polymers by sonication, we synthesized the nanoparticles that showed switch-like functions of the fluorescence intensity (and/or lifetime) as the temperature, with high switch on-to-off ratio. We also investigated various factors that might change the temperature thresholds (Tth) of the switch functions, in order to control Tth during synthesis. RESULTS: These nanoparticles showed excellent temperature-switchable properties of fluorescence intensity and/or lifetime. Meanwhile, some factors (i.e., pluronic categories and nanoparticles' concentration) significantly affected the nanoparticles' Tths while other (i.e., fluorophore categories) that weakly affected Tths. CONCLUSIONS: By selecting appropriate pluronic categories and adjusting the nanoparticle's concentration, we can synthesize the nanoparticles with a wide range of Tths. These temperature-switchable fluorescence nanoparticles can be used for biomedical imaging and in vivo tissue temperature sensing/imaging.

Force-induced charge carrier storage: a new route for stress recording.

Stress sensing is the basis of human-machine interface, biomedical engineering, and mechanical structure detection systems. Stress sensing based on mechanoluminescence (ML) shows significant advantages of distributed detection and remote response to mechanical stimuli and is thus expected to be a key technology of next-generation tactile sensors and stress recorders. However, the instantaneous photon emission in ML materials generally requires real-time recording with a photodetector, thus limiting their application fields to real-time stress sensing. In this paper, we report a force-induced charge carrier storage (FICS) effect in deep-trap ML materials, which enables storage of the applied mechanical energy in deep traps and then release of the stored energy as photon emission under thermal stimulation. The FICS effect was confirmed in five ML materials with piezoelectric structures, efficient emission centres and deep trap distributions, and its mechanism was investigated through detailed spectroscopic characterizations. Furthermore, we demonstrated three applications of the FICS effect in electronic signature recording, falling point monitoring and vehicle collision recording, which exhibited outstanding advantages of distributed recording, long-term storage, and no need for a continuous power supply. The FICS effect reported in this paper provides not only a breakthrough for ML materials in the field of stress recording but also a new idea for developing mechanical energy storage and conversion systems.

Miniscope3D: optimized single-shot miniature 3D fluorescence microscopy.

Miniature fluorescence microscopes are a standard tool in systems biology. However, widefield miniature microscopes capture only 2D information, and modifications that enable 3D capabilities increase the size and weight and have poor resolution outside a narrow depth range. Here, we achieve the 3D capability by replacing the tube lens of a conventional 2D Miniscope with an optimized multifocal phase mask at the objective's aperture stop. Placing the phase mask at the aperture stop significantly reduces the size of the device, and varying the focal lengths enables a uniform resolution across a wide depth range. The phase mask encodes the 3D fluorescence intensity into a single 2D measurement, and the 3D volume is recovered by solving a sparsity-constrained inverse problem. We provide methods for designing and fabricating the phase mask and an efficient forward model that accounts for the field-varying aberrations in miniature objectives. We demonstrate a prototype that is 17 mm tall and weighs 2.5 grams, achieving 2.76 µm lateral, and 15 µm axial resolution across most of the 900 × 700 × 390 µm3 volume at 40 volumes per second. The performance is validated experimentally on resolution targets, dynamic biological samples, and mouse brain tissue. Compared with existing miniature single-shot volume-capture implementations, our system is smaller and lighter and achieves a more than 2× better lateral and axial resolution throughout a 10× larger usable depth range. Our microscope design provides single-shot 3D imaging for applications where a compact platform matters, such as volumetric neural imaging in freely moving animals and 3D motion studies of dynamic samples in incubators and lab-on-a-chip devices.

Incoherent excess noise spectrally encodes broadband light sources.

Across optics and photonics, excess intensity noise is often considered a liability. Here, we show that excess noise in broadband supercontinuum and superluminescent diode light sources encodes each spectral channel with unique intensity fluctuations, which actually serve a useful purpose. Specifically, we report that excess noise correlations can both characterize the spectral resolution of spectrometers and enable cross-calibration of their wavelengths across a broad bandwidth. Relative to previous methods that use broadband interferometry and narrow linewidth lasers to characterize and calibrate spectrometers, our approach is simple, comprehensive, and rapid enough to be deployed during spectrometer alignment. First, we employ this approach to aid alignment and reduce the depth-dependent degradation of the sensitivity and axial resolution in a spectrometer-based optical coherence tomography (OCT) system, revealing a new outer retinal band. Second, we achieve a pixel-to-pixel correspondence between two otherwise disparate spectrometers, enabling a robust comparison of their respective measurements. Thus, excess intensity noise has useful applications in optics and photonics.

Spectrum projection with a bandgap-gradient perovskite cell for colour perception.

Optoelectronic devices for light or spectral signal detection are desired for use in a wide range of applications, including sensing, imaging, optical communications, and in situ characterization. However, existing photodetectors indicate only light intensities, whereas multiphotosensor spectrometers require at least a chip-level assembly and can generate redundant signals for applications that do not need detailed spectral information. Inspired by human visual and psychological light perceptions, the compression of spectral information into representative intensities and colours may simplify spectrum processing at the device level. Here, we propose a concept of spectrum projection using a bandgap-gradient semiconductor cell for intensity and colour perception. Bandgap-gradient perovskites, prepared by a halide-exchanging method via dipping in a solution, are developed as the photoactive layer of the cell. The fabricated cell produces two output signals: one shows linear responses to both photon energy and flux, while the other depends on only photon flux. Thus, by combining the two signals, the single device can project the monochromatic and broadband spectra into the total photon fluxes and average photon energies (i.e., intensities and hues), which are in good agreement with those obtained from a commercial photodetector and spectrometer. Under changing illumination in real time, the prepared device can instantaneously provide intensity and hue results. In addition, the flexibility and chemical/bio-sensing of the device via colour comparison are demonstrated. Therefore, this work shows a human visual-like method of spectrum projection and colour perception based on a single device, providing a paradigm for high-efficiency spectrum-processing applications.

Multifocal structured illumination optoacoustic microscopy.

Optoacoustic (OA) imaging has the capacity to effectively bridge the gap between macroscopic and microscopic realms in biological imaging. High-resolution OA microscopy has so far been performed via point-by-point scanning with a focused laser beam, thus greatly restricting the achievable imaging speed and/or field of view. Herein we introduce multifocal structured illumination OA microscopy (MSIOAM) that attains real-time 3D imaging speeds. For this purpose, the excitation laser beam is shaped to a grid of focused spots at the tissue surface by means of a beamsplitting diffraction grating and a condenser and is then scanned with an acousto-optic deflector operating at kHz rates. In both phantom and in vivo mouse experiments, a 10 mm wide volumetric field of view was imaged with 15 Hz frame rate at 28 µm spatial resolution. The proposed method is expected to greatly aid in biological investigations of dynamic functional, kinetic, and metabolic processes across multiple scales.

A versatile photodetector assisted by photovoltaic and bolometric effects.

The advent of low-dimensional materials with peculiar structure and superb band properties provides a new canonical form for the development of photodetectors. However, the limited exploitation of basic properties makes it difficult for devices to stand out. Here, we demonstrate a hybrid heterostructure with ultrathin vanadium dioxide film and molybdenum ditelluride nanoflake. Vanadium dioxide is a classical semiconductor with a narrow bandgap, a high temperature coefficient of resistance, and phase transformation. Molybdenum ditelluride, a typical two-dimensional material, is often used to construct optoelectronic devices. The heterostructure can realize three different functional modes: (i) the p-n junction exhibits ultrasensitive detection (450 nm-2 µm) with a dark current down to 0.2 pA and a response time of 17 µs, (ii) the Schottky junction works stably under extreme conditions such as a high temperature of 400 K, and (iii) the bolometer shows ultrabroad spectrum detection exceeding 10 µm. The flexible switching between the three modes makes the heterostructure a potential candidate for next-generation photodetectors from visible to longwave infrared radiation (LWIR). This type of photodetector combines versatile detection modes, shedding light on the hybrid application of novel and traditional materials, and is a prototype of advanced optoelectronic devices.

Dynamic full-field optical coherence tomography: 3D live-imaging of retinal organoids.

Optical coherence tomography offers astounding opportunities to image the complex structure of living tissue but lacks functional information. We present dynamic full-field optical coherence tomography as a technique to noninvasively image living human induced pluripotent stem cell-derived retinal organoids. Coloured images with an endogenous contrast linked to organelle motility are generated, with submicrometre spatial resolution and millisecond temporal resolution, creating a way to identify specific cell types in living tissue via their function.

Wolf phase tomography (WPT) of transparent structures using partially coherent illumination.

In 1969, Emil Wolf proposed diffraction tomography using coherent holographic imaging to extract 3D information from transparent, inhomogeneous objects. In the same era, the Wolf equations were first used to describe the propagation correlations associated with partially coherent fields. Combining these two concepts, we present Wolf phase tomography (WPT), which is a method for performing diffraction tomography using partially coherent fields. WPT reconstruction works directly in the space-time domain, without the need for Fourier transformation, and decouples the refractive index (RI) distribution from the thickness of the sample. We demonstrate the WPT principle using the data acquired by a quantitative-phase-imaging method that upgrades an existing phase-contrast microscope by introducing controlled phase shifts between the incident and scattered fields. The illumination field in WPT is partially spatially coherent (emerging from a ring-shaped pupil function) and of low temporal coherence (white light), and as such, it is well suited for the Wolf equations. From three intensity measurements corresponding to different phase-contrast frames, the 3D RI distribution is obtained immediately by computing the Laplacian and second time derivative of the measured complex correlation function. We validate WPT with measurements of standard samples (microbeads), spermatozoa, and live neural cultures. The high throughput and simplicity of this method enables the study of 3D, dynamic events in living cells across the entire multiwell plate, with an RI sensitivity on the order of 10-5.

Lensless light-field imaging through diffuser encoding.

Microlens array-based light-field imaging has been one of the most commonly used and effective technologies to record high-dimensional optical signals for developing various potential high-performance applications in many fields. However, the use of a microlens array generally suffers from an intrinsic trade-off between the spatial and angular resolutions. In this paper, we concentrate on exploiting a diffuser to explore a novel modality for light-field imaging. We demonstrate that the diffuser can efficiently angularly couple incident light rays into a detected image without needing any lens. To characterize and analyse this phenomenon, we establish a diffuser-encoding light-field transmission model, in which four-dimensional light fields are mapped into two-dimensional images via a transmission matrix describing the light propagation through the diffuser. Correspondingly, a calibration strategy is designed to flexibly determine the transmission matrix, so that light rays can be computationally decoupled from a detected image with adjustable spatio-angular resolutions, which are unshackled from the resolution limitation of the sensor. The proof-of-concept approach indicates the possibility of using scattering media for lensless four-dimensional light-field recording and processing, not just for two- or three-dimensional imaging.

Multifocal photoacoustic microscopy using a single-element ultrasonic transducer through an ergodic relay.

Optical-resolution photoacoustic microscopy (OR-PAM) has demonstrated high-spatial-resolution imaging of optical absorption in biological tissue. To date, most OR-PAM systems rely on mechanical scanning with confocally aligned optical excitation and ultrasonic detection, limiting the wide-field imaging speed of these systems. Although several multifocal OR-PA (MFOR-PA) systems have attempted to address this limitation, they are hindered by the complex design in a constrained physical space. Here, we present a two-dimensional (2D) MFOR-PAM system that utilizes a 2D microlens array and an acoustic ergodic relay. Using a single-element ultrasonic transducer, this system can detect PA signals generated from 400 optical foci in parallel and then raster scan the optical foci patterns to form an MFOR-PAM image. This system improves the imaging resolution of an acoustic ergodic relay system from 220 to 13 µm and enables 400-folds shorter scanning time than that of a conventional OR-PAM system at the same resolution and laser repetition rate. We demonstrated the imaging ability of the system with both in vitro and in vivo experiments.