Optical Detection of Cancer Cells Using Lab-on-a-Chip.

The global need for accurate and efficient cancer cell detection in biomedicine and clinical diagnosis has driven extensive research and technological development in the field. Precision, high-throughput, non-invasive separation, detection, and classification of individual cells are critical requirements for successful technology. Lab-on-a-chip devices offer enormous potential for solving biological and medical problems and have become a priority research area for microanalysis and manipulating cells. This paper reviews recent developments in the detection of cancer cells using the microfluidics-based lab-on-a-chip method, focusing on describing and explaining techniques that use optical phenomena and a plethora of probes for sensing, amplification, and immobilization. The paper describes how optics are applied in each experimental method, highlighting their advantages and disadvantages. The discussion includes a summary of current challenges and prospects for cancer diagnosis.

Thin film notch filters as platforms for biological image processing.

Many image processing operations involve the modification of the spatial frequency content of images. Here we demonstrate object-plane spatial frequency filtering utilizing the angular sensitivity of a commercial spectral bandstop filter. This approach to all-optical image processing is shown to generate real-time pseudo-3D images of transparent biological and other samples, such as human cervical cancer cells. This work demonstrates the potential of non-local, non-interferometric approaches to image processing for uses in label-free biological cell imaging and dynamical monitoring.

Selective IR super-resolution imaging of ß-keratins at the bulk or interface in feather detected by using a nonlinear optical process.

We developed the new IR super-resolution microscope by using a 4-wave mixing (4-wave), which is a third-order nonlinear optical process, and carried out the IR super-resolution imaging of the cross section of the rachis of an avian feather. We clearly observed strong signals in the entire region of the rachis at the amide I vibration of ß-keratin in both of the XXYY and YYXX polarization combination. These results are different from images detected by using the vibrational sum-frequency generation (VSFG) method. While the VSFG imaging detects molecules only from the interface, the 4-wave method enables us to observe the signal from the bulk area. We concluded that the four repeating units of ß-keratins in the bulk area which are suggested by X-ray diffraction studies are visualized in the 4-wave detected method. We also applied two IR super-resolution microscopies for the barb and discuss the site dependence of the orientation, distribution and concentration of ß-keratin.

Glassfrogs conceal blood in their liver to maintain transparency.

Transparency in animals is a complex form of camouflage involving mechanisms that reduce light scattering and absorption throughout the organism. In vertebrates, attaining transparency is difficult because their circulatory system is full of red blood cells (RBCs) that strongly attenuate light. Here, we document how glassfrogs overcome this challenge by concealing these cells from view. Using photoacoustic imaging to track RBCs in vivo, we show that resting glassfrogs increase transparency two- to threefold by removing ~89% of their RBCs from circulation and packing them within their liver. Vertebrate transparency thus requires both see-through tissues and active mechanisms that "clear" respiratory pigments from these tissues. Furthermore, glassfrogs' ability to regulate the location, density, and packing of RBCs without clotting offers insight in metabolic, hemodynamic, and blood-clot research.

Dual division of focal plane polarimeters-based collinear reflection Mueller matrix fast imaging microscope.

SIGNIFICANCE: Reflection Mueller matrix imaging is suitable for characterizing the microstructure of bulk specimens and probing dynamic processes in living animals, there are always demands for speed and accuracy for such applications to avoid possible artifacts and reveal a sample's intrinsic properties. AIM: To demonstrate a design of collinear reflection Mueller matrix fast imaging microscope based on dual division of focal plane (DoFP) polarimeters (DoFPs-CRMMM) which has high measurement speed and accuracy. APPROACH: In DoFPs-CRMMM, to improve the measurement speed, we applied the dual DoFP polarimeters design on the collinear reflection system for the first time to achieve fast imaging in about 2 s. To improve the measurement accuracy, we improved the double-pass eigenvalue calibration method (dp-ECM) by background light correction, and explored the optimization of the set of reference samples. RESULTS: DoFPs-CRMMM was applied to measure the standard polarization samples and monitor the tissue optical clearing process of an artificial layered bulk tissue. Results show that the system has satisfactory performance which can capture the variation of polarization properties during the dynamic process. CONCLUSIONS: We present the establishment and demo application of DoFPs-CRMMM. The measurement speed can be further accelerated for potential applications in monitoring dynamic processes or living biomedical systems.

Quantifying tissue optical properties of human heads in vivo using continuous-wave near-infrared spectroscopy and subject-specific three-dimensional Monte Carlo models.

SIGNIFICANCE: Quantifying subject-specific optical properties (OPs) including absorption and transport scattering coefficients of tissues in the human head could improve the modeling of photon propagation for the analysis of functional near-infrared spectroscopy (fNIRS) data and dosage quantification in therapeutic applications. Current methods employ diffuse approximation, which excludes a low-scattering cerebrospinal fluid compartment and causes errors. AIM: This work aims to quantify OPs of the scalp, skull, and gray matter in vivo based on accurate Monte Carlo (MC) modeling. APPROACH: Iterative curve fitting was applied to quantify tissue OPs from multidistance continuous-wave NIR reflectance spectra. An artificial neural network (ANN) was trained using MC-simulated reflectance values based on subject-specific voxel-based tissue models to replace MC simulations as the forward model in curve fitting. To efficiently generate sufficient data for training the ANN, the efficiency of MC simulations was greatly improved by white MC simulations, increasing the detectors' acceptance angle, and building a lookup table for interpolation. RESULTS: The trained ANN was six orders of magnitude faster than the original MC simulations. OPs of the three tissue compartments were quantified from NIR reflectance spectra measured at the forehead of five healthy subjects and their uncertainties were estimated. CONCLUSIONS: This work demonstrated an MC-based iterative curve fitting method to quantify subject-specific tissue OPs in-vivo, with all OPs except for scattering coefficients of scalp within the ranges reported in the literature, which could aid the modeling of photon propagation in human heads.

Combined person classification with airborne optical sectioning.

Fully autonomous drones have been demonstrated to find lost or injured persons under strongly occluding forest canopy. Airborne optical sectioning (AOS), a novel synthetic aperture imaging technique, together with deep-learning-based classification enables high detection rates under realistic search-and-rescue conditions. We demonstrate that false detections can be significantly suppressed and true detections boosted by combining classifications from multiple AOS-rather than single-integral images. This improves classification rates especially in the presence of occlusion. To make this possible, we modified the AOS imaging process to support large overlaps between subsequent integrals, enabling real-time and on-board scanning and processing of groundspeeds up to 10 m/s.

Synthesis Mechanisms, Structural Models, and Photothermal Therapy Applications of Top-Down Carbon Dots from Carbon Powder, Graphite, Graphene, and Carbon Nanotubes.

In this study, top-down syntheses of carbon dots (CDs) from four different carbon precursors, namely, carbon nano powders, graphite, graphene, and carbon nanotubes, were carried out. Systematic study demonstrated that the optical properties and surface functionalities of the CDs were quite similar and mainly influenced by the synthesis method, while the sizes, morphologies, chemical compositions, and core structures of the CDs were heavily influenced by the carbon precursors. On the basis of these studies, the formation processes and structural models of these four top-down CDs were proposed. The cell cytotoxicity and photothermal conversion efficiency of these CDs were also carefully evaluated, demonstrating their potential applications in photothermal therapy.

3D printing of resilient biogels for omnidirectional and exteroceptive soft actuators.

Soft robotics greatly benefits from nature as a source of inspiration, introducing innate means of safe interaction between robotic appliances and living organisms. In contrast, the materials involved are often nonbiodegradable or stem from nonrenewable resources, contributing to an ever-growing environmental footprint. Furthermore, conventional manufacturing methods, such as mold casting, are not suitable for replicating or imitating the complexity of nature's creations. Consequently, the inclusion of sustainability concepts alongside the development of new fabrication procedures is required. We report a customized 3D-printing process based on fused deposition modeling, printing a fully biodegradable gelatin-based hydrogel (biogel) ink into dimensionally stable, complex objects. This process enables fast and cost-effective prototyping of resilient, soft robotic applications from gels that stretch to six times their original length, as well as an accessible recycling procedure with zero waste. We present printed pneumatic actuators performing omnidirectional movement at fast response times (less than a second), featuring integrated 3D-printed stretchable waveguides, capable of both proprio- and exteroception. These soft devices are endowed with dynamic real-time control capable of automated search-and-wipe routines to detect and remove obstacles. They can be reprinted several times or disposed of hazard-free at the end of their lifetime, potentially unlocking a sustainable future for soft robotics.

Tailoring noble metal nanoparticle designs to enable sensitive lateral flow immunoassay.

Lateral flow immunoassay (LFIA) with gold nanoparticles (AuNPs) as signal reporters is a popular point-of-care diagnostic technique. However, given the weak absorbance of traditional 20-40 nm spherical AuNPs, their sensitivity is low, which greatly limits the wide application of AuNP-based LFIA. With the rapid advances in materials science and nanotechnology, the synthesis of noble metal nanoparticles (NMNPs) has enhanced physicochemical properties such as optical, plasmonic, catalytic, and multifunctional activity by simply engineering their physical parameters, including the size, shape, composition, and external structure. Using these engineered NMNPs as an alternative to traditional AuNPs, the sensitivity of LFIA has been significantly improved, thereby greatly expanding the working range and application scenarios of LFIA, particularly in trace analysis. Therefore, in this review, we will focus on the design of engineered NMNPs and their demonstration in improving LFIA. We highlight the strategies available for tailoring NMNP designs, the effect of NMNP engineering on their performance, and the working principle of each engineering design for enhancing LFIA. Finally, current challenges and future improvements in this field are briefly discussed.

Variations in tissue optical parameters with the incident power of an infrared laser.

Infrared (IR) lasers are extensively utilized as an effective tool in many medical practices. Nevertheless, light penetration into the inspected tissue, which is highly affected by tissue optical properties, is a crucial factor for successful optical procedures. Although the optical properties are highly wavelength-dependent, they can be affected by the power of the incident laser. The present study demonstrates a considerable change in the scattering and absorption coefficients as a result of varying the incident laser power probing into biological samples at a constant laser wavelength (808 nm). The optical parameters were investigated using an integrating sphere and Kubelka-Munk model. Additionally, fluence distribution at the sample's surface was modeled using COMSOL-multiphysics software. The experimental results were validated using Receiver Operating Characteristic (ROC) curves and Monte-Carlo simulation. The results showed that tissue scattering coefficient decreases as the incident laser power increases while the absorption coefficient experienced a slight change. Moreover, the penetration depth increases with the optical parameters. The reduction in the scattering coefficients leads to wider and more diffusive fluence rate distribution at the tissue surface. The simulation results showed a good agreement with the experimental data and revealed that tissue anisotropy may be responsible for this scattering reduction. The present findings could be considered in order for the specialists to accurately specify the laser optical dose in various biomedical applications.

Circularly polarised luminescence laser scanning confocal microscopy to study live cell chiral molecular interactions.

The molecular machinery of life is founded on chiral building blocks, but no experimental technique is currently available to distinguish or monitor chiral systems in live cell bio-imaging studies. Luminescent chiral molecules encode a unique optical fingerprint within emitted circularly polarized light (CPL) carrying information about the molecular environment, conformation, and binding state. Here, we present a CPL Laser Scanning Confocal Microscope (CPL-LSCM) capable of simultaneous chiroptical contrast based live-cell imaging of endogenous and engineered CPL-active cellular probes. Further, we demonstrate that CPL-active probes can be activated using two-photon excitation, with complete CPL spectrum recovery. The combination of these two milestone results empowers the multidisciplinary imaging community, allowing the study of chiral interactions on a sub-cellular level in a new (chiral) light.

Light-driven carbon nitride microswimmers with propulsion in biological and ionic media and responsive on-demand drug delivery.

We propose two-dimensional poly(heptazine imide) (PHI) carbon nitride microparticles as light-driven microswimmers in various ionic and biological media. Their high-speed (15 to 23 micrometer per second; 9.5 ± 5.4 body lengths per second) swimming in multicomponent ionic solutions with concentrations up to 5 M and without dedicated fuels is demonstrated, overcoming one of the bottlenecks of previous light-driven microswimmers. Such high ion tolerance is attributed to a favorable interplay between the particle's textural and structural nanoporosity and optoionic properties, facilitating ionic interactions in solutions with high salinity. Biocompatibility of these microswimmers is validated by cell viability tests with three different cell lines and primary cells. The nanopores of the swimmers are loaded with a model cancer drug, doxorubicin (DOX), resulting in a high (185%) loading efficiency without passive release. Controlled drug release is reported under different pH conditions and can be triggered on-demand by illumination. Light-triggered, boosted release of DOX and its active degradation products are demonstrated under oxygen-poor conditions using the intrinsic, environmentally sensitive and light-induced charge storage properties of PHI, which could enable future theranostic applications in oxygen-deprived tumor regions. These organic PHI microswimmers simultaneously address the current light-driven microswimmer challenges of high ion tolerance, fuel-free high-speed propulsion in biological media, biocompatibility, and controlled on-demand cargo release toward their biomedical, environmental, and other potential applications.

One-Step Approach to Prepare Transparent Conductive Regenerated Silk Fibroin/PEDOT:PSS Films for Electroactive Cell Culture.

Silk fibroin (SF)-based electroactive biomaterials with favorable electroconductive property and transparency have great potential applications for cell culture and tissue engineering. Poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) is an excellent candidate as a conductive component, which has been widely used in the field of bioelectronics; however, it is hard to be directly coated onto the surface of regenerated SF (RSF) materials with good stability under a cell culture environment. In this study, a one-step facile PEDOT:PSS modification approach for RSF films based on a suitable post-treatment process of RSF was developed. PEDOT:PSS was successfully embedded and fixed into the shallow surface of an RSF film, forming a tightly conjunct conductive layer on the film surface based on the conformation transition of RSF during the post-treatment process. The conductive layer demonstrated a PSS-rich surface and a PEDOT-rich bulk structure and showed excellent stability under a cell culture environment. More specifically, the robust RSF/PEDOT:PSS film achieved in the post-treatment formula with 70% ethanol proportion possessed best comprehensive properties such as a sheet resistance of 3.833 × 103 Ω/square, a conductivity of 1.003 S/cm, and transmittance over 80% at maximum in the visible range. This kind of electroactive biomaterial also showed good electrochemical stability and degradable properties. Moreover, pheochromocytoma-derived cell line (PC12) cells were cultured on the RSF/PEDOT:PSS film, and an effective electrical stimulation cell response was demonstrated. The facile preparation strategy and the good electroconductive property and transparency make this RSF/PEDOT:PSS film an ideal candidate for neuronal tissue engineering and further for biomedical applications.

Plasmonic Optoelectronic Memristor Enabling Fully Light-Modulated Synaptic Plasticity for Neuromorphic Vision.

Exploration of optoelectronic memristors with the capability to combine sensing and processing functions is required to promote development of efficient neuromorphic vision. In this work, the authors develop a plasmonic optoelectronic memristor that relies on the effects of localized surface plasmon resonance (LSPR) and optical excitation in an Ag-TiO2 nanocomposite film. Fully light-induced synaptic plasticity (e.g., potentiation and depression) under visible and ultraviolet light stimulations is demonstrated, which enables the functional combination of visual sensing and low-level image pre-processing (including contrast enhancement and noise reduction) in a single device. Furthermore, the light-gated and electrically-driven synaptic plasticity can be performed in the same device, in which the spike-timing-dependent plasticity (STDP) learning functions can be reversibly modulated by visible and ultraviolet light illuminations. Thereby, the high-level image processing function, i.e., image recognition, can also be performed in this memristor, whose recognition rate and accuracy are obviously enhanced as a result of image pre-processing and light-gated STDP enhancement. Experimental analysis shows that the memristive switching mechanism under optical stimulation can be attributed to the oxidation/reduction of Ag nanoparticles due to the effects of LSPR and optical excitation. The authors' work proposes a new type of plasmonic optoelectronic memristor with fully light-modulated capability that may promote the future development of efficient neuromorphic vision.

Cross-Axis projection error in optically pumped magnetometers and its implication for magnetoencephalography systems.

Optically pumped magnetometers (OPMs) developed for magnetoencephalography (MEG) typically operate in the spin-exchange-relaxation-free (SERF) regime and measure a magnetic field component perpendicular to the propagation axis of the optical-pumping photons. The most common type of OPM for MEG employs alkali atoms, e.g. 87Rb, as the sensing element and one or more lasers for preparation and interrogation of the magnetically sensitive states of the alkali atoms ensemble. The sensitivity of the OPM can be greatly enhanced by operating it in the SERF regime, where the alkali atoms' spin exchange rate is much faster than the Larmor precession frequency. The SERF regime accommodates remnant static magnetic fields up to ±5 nT. However, in the presented work, through simulation and experiment, we demonstrate that multi-axis magnetic signals in the presence of small remnant static magnetic fields, not violating the SERF criteria, can introduce significant error terms in OPM's output signal. We call these deterministic errors cross-axis projection errors (CAPE), where magnetic field components of the MEG signal perpendicular to the nominal sensing axis contribute to the OPM signal giving rise to substantial amplitude and phase errors. Furthermore, through simulation, we have discovered that CAPE can degrade localization and calibration accuracy of OPM-based magnetoencephalography (OPM-MEG) systems.

Self-rated quality of vision and optical phenomena intensity of diffractive presbyopia-correcting IOLs: EDoF, trifocal vs panfocal.

PURPOSE: To investigate the self-rated quality of vision (SQV) and optical phenomena intensity of 3 diffractive multifocal intraocular lenses (mIOLs). SETTING: Department of Ophthalmology, Goethe University Frankfurt, Germany. DESIGN: Prospective comparative case series. METHODS: Patients who had bilateral implantation of a diffractive extended depth-of-focus (EDoF), trifocal, or panfocal mIOL were assessed. Outcome parameters were SQV, symptom intensity of optical phenomena under 3 lighting conditions, quality of everyday lifestyle activities, spectacle independence (SI), and contrast sensitivity (CS). RESULTS: The study comprised 108 eyes. The 3 lenses provided good total SQV under all lighting conditions. EDoF patients reported a slightly better total SQV (EDoF: 9.8 ± 6.67, trifocal: 22.2 ± 7.09, panfocal: 19.6 ± 16.25 visual analog scale, P = .041). A similar percentage of patients reported the presence of optical phenomena with no difference between mIOLs ( P > .05). EDoF, trifocal, and panfocal patients rated symptom intensity of optical phenomena mild to moderate under all lighting conditions; however, EDoF patients reported a lower symptom intensity of halos ( P < .05). Reported quality of everyday lifestyle activities and CS were comparable ( P < .05). All panfocal and trifocal patients (100%) achieved complete SI, whereas almost half (44%) of the EDoF patients used reading spectacles. CONCLUSIONS: Diffractive EDoF, trifocal, and panfocal mIOLs provided good total SQV with mild to moderate intensity of optical phenomena under all lighting conditions. EDoF patients experienced the same percentage of optical phenomena but reported a weaker symptom intensity of halos and better night-driving ability. EDoF patients would all choose the same IOL, although a significant number of them needed reading spectacles, indicating that SI is not the main factor that determines patient selection of IOLs.