Mapping cutaneous field carcinogenesis of nonmelanoma skin cancer using mesoscopic imaging of pro-inflammation cues.

Nonmelanoma skin cancers remain the most widely diagnosed types of cancers globally. Thus, for optimal patient management, it has become imperative that we focus our efforts on the detection and monitoring of cutaneous field carcinogenesis. The concept of field cancerization (or field carcinogenesis), introduced by Slaughter in 1953 in the context of oral cancer, suggests that invasive cancer may emerge from a molecularly and genetically altered field affecting a substantial area of underlying tissue including the skin. A carcinogenic field alteration, present in precancerous tissue over a relatively large area, is not easily detected by routine visualization. Conventional dermoscopy and microscopy imaging are often limited in assessing the entire carcinogenic landscape. Recent efforts have suggested the use of noninvasive mesoscopic (between microscopic and macroscopic) optical imaging methods that can detect chronic inflammatory features to identify pre-cancerous and cancerous angiogenic changes in tissue microenvironments. This concise review covers major types of mesoscopic optical imaging modalities capable of assessing pro-inflammatory cues by quantifying blood haemoglobin parameters and hemodynamics. Importantly, these imaging modalities demonstrate the ability to detect angiogenesis and inflammation associated with actinically damaged skin. Representative experimental preclinical and human clinical studies using these imaging methods provide biological and clinical relevance to cutaneous field carcinogenesis in altered tissue microenvironments in the apparently normal epidermis and dermis. Overall, mesoscopic optical imaging modalities assessing chronic inflammatory hyperemia can enhance the understanding of cutaneous field carcinogenesis, offer a window of intervention and monitoring for actinic keratoses and nonmelanoma skin cancers and maximise currently available treatment options.

A Pearl Spectrometer.

Information recovery from incomplete measurements, typically performed by a numerical means, is beneficial in a variety of classical and quantum signal processing. Random and sparse sampling with nanophotonic and light scattering approaches has received attention to overcome the hardware limitations of conventional spectrometers and hyperspectral imagers but requires high-precision nanofabrications and bulky media. We report a simple spectral information processing scheme in which light transport through an Anderson-localized medium serves as an entropy source for compressive sampling directly in the frequency domain. As implied by the "lustrous" reflection originating from the exquisite multilayered nanostructures, a pearl (or mother-of-pearl) allows us to exploit the spatial and spectral intensity fluctuations originating from strong light localization for extracting salient spectral information with a compact and thin form factor. Pearl-inspired light localization in low-dimensional structures can offer an alternative of spectral information processing by hybridizing digital and physical properties at a material level.

Transgenic and Diet-Enhanced Silk Production for Reinforced Biomaterials: A Metamaterial Perspective.

Silk fibers, which are protein-based biopolymers produced by spiders and silkworms, are fascinating biomaterials that have been extensively studied for numerous biomedical applications. Silk fibers often have remarkable physical and biological properties that typical synthetic materials do not exhibit. These attributes have prompted a wide variety of silk research, including genetic engineering, biotechnological synthesis, and bioinspired fiber spinning, to produce silk proteins on a large scale and to further enhance their properties. In this review, we describe the basic properties of spider silk and silkworm silk and the important production methods for silk proteins. We discuss recent advances in reinforced silk using silkworm transgenesis and functional additive diets with a focus on biomedical applications. We also explain that reinforced silk has an analogy with metamaterials such that user-designed atypical responses can be engineered beyond what naturally occurring materials offer. These insights into reinforced silk can guide better engineering of superior synthetic biomaterials and lead to discoveries of unexplored biological and medical applications of silk.

Compressive recovery of smartphone RGB spectral sensitivity functions.

Spectral response (or sensitivity) functions of a three-color image sensor (or trichromatic camera) allow a mapping from spectral stimuli to RGB color values. Like biological photosensors, digital RGB spectral responses are device dependent and significantly vary from model to model. Thus, the information on the RGB spectral response functions of a specific device is vital in a variety of computer vision as well as mobile health (mHealth) applications. Theoretically, spectral response functions can directly be measured with sophisticated calibration equipment in a specialized laboratory setting, which is not easily accessible for most application developers. As a result, several mathematical methods have been proposed relying on standard color references. Typical optimization frameworks with constraints are often complicated, requiring a large number of colors. We report a compressive sensing framework in the frequency domain for accurately predicting RGB spectral response functions only with several primary colors. Using a scientific camera, we first validate the estimation method with direct spectral sensitivity measurements and ensure that the root mean square errors between the ground truth and recovered RGB spectral response functions are negligible. We further recover the RGB spectral response functions of smartphones and validate with an expanded color checker reference. We expect that this simple yet reliable estimation method of RGB spectral sensitivity can easily be applied for color calibration and standardization in machine vision, hyperspectral filters, and mHealth applications that capitalize on the built-in cameras of smartphones.

Visible light biophotosensors using biliverdin from Antheraea yamamai.

We report an endogenous photoelectric biomolecule and demonstrate that such a biomolecule can be used to detect visible light. We identify the green pigment abundantly present in natural silk cocoons of Antheraea yamamai (Japanese oak silkmoth) as biliverdin, using mass spectroscopy and optical spectroscopy. Biliverdin extracted from the green silk cocoons generates photocurrent upon light illumination with distinct colors. We further characterize the basic performance, responsiveness, and stability of the biliverdin-based biophotosensors at a photovoltaic device level using blue, green, orange, and red light illumination. Biliverdin could potentially serve as an optoelectric biomolecule toward the development of next-generation implantable photosensors and artificial photoreceptors.

Controlling Random Lasing with Three-Dimensional Plasmonic Nanorod Metamaterials.

Plasmonics has brought revolutionary advances to laser science by enabling deeply subwavelength nanolasers through surface plasmon amplification. However, the impact of plasmonics on other promising laser systems has so far remained elusive. Here, we present a class of random lasers enabled by three-dimensional plasmonic nanorod metamaterials. While dense metallic nanostructures are usually detrimental to laser performance due to absorption losses, here the lasing threshold keeps decreasing as the volume fraction of metal is increased up to ∼0.07. This is ∼460 times higher than the optimal volume fraction reported thus far. The laser supports spatially confined lasing modes and allows for efficient modulation of spectral profiles by simply tuning the polarization of the pump light. Full-field speckle-free imaging at micron-scales has been achieved by using plasmonic random lasers as the illumination sources. Our findings show that plasmonic metamaterials hold potential to enable intriguing coherent optical sources.

Telecentric suppression of diffuse light in imaging of highly anisotropic scattering media.

The telecentric lens, which was originally used in the machine vision industry, has often been utilized in biomedical imaging systems due to its commonly known properties, such as large transverse field of view, constant magnification, and long working distance. However, its potential advantages in optical imaging of biological tissue, which is highly diffusive, have not been fully explored. We revisit the idea that a telecentric lens system can bring an alternative yet simple method for reducing unwanted scattering or diffuse light in biological tissue, owing to its highly anisotropic scattering properties. Using biological tissue and tissue phantoms, we demonstrate advantages attributed to the use of telecentric lens in tissue imaging compared with imaging using conventional nontelecentric optics. Directional or angular gating (or filtering) using a telecentric lens is beneficial for removing a portion of diffuse light in highly anisotropic scattering media with high values of the scattering anisotropy factor. We envision that a telecentric lens could be potentially incorporated into an instrument of modest design and cost, increasing rapid practical adoption.

Dispersion Curve Engineering of TiO2/Silver Hybrid Substrates for Enhanced Surface Plasmon Resonance Detection.

As surface plasmon resonance (SPR)-based biosensors are well translated into biological, chemical, environmental, and clinical fields, it is critical to further realize stable and sustainable systems, avoiding oxidation susceptibility of metal films-in particular, silver substrates. We report an enhanced SPR detection performance by incorporating a TiO2 layer on top of a thin silver film. A uniform TiO2 film fabricated by electron beam evaporation at room temperature is an effective alternative in bypassing oxidation of a silver film. Based on our finding that the sensor sensitivity is strongly correlated with the slope of dispersion curves, SPR sensing results obtained by parylene film deposition shows that TiO2/silver hybrid substrates provide notable sensitivity improvement compared to a conventional bare silver film, which confirms the possibility of engineering the dispersion characteristic according to the incidence wavelength. The reported SPR structures with TiO2 films enhance the sensitivity significantly in water and air environments and its overall qualitative trend in sensitivity improvement is consistent with numerical simulations. Thus, we expect that our approach can extend the applicability of TiO2-mediated SPR biosensors to highly sensitive detection for biomolecular binding events of low concentrations, while serving a practical and reliable biosensing platform.

Excitation of multiple resonances in 1D Anderson localized systems for efficient light amplification.

Excitation of hybridized multiple resonances can be an effective route for coherent light generation in irregular 1D systems larger than the localization length of light. Necklace states are often considered to have nonlocalized states. However, we propose that some hybridized/coupled states can have high-resonant tunneling with spatially extended fields. If strong localization properties are preserved in hybridized resonances, the excitation of such states allows for deposition of the excitation energy deep into the structure and spatial overlap with local gain regions. This result could allow for better utilizing hybridized resonances in biological or natural photonic systems.

Heteronanostructured Field-Effect Transistors for Enhancing Entropy and Parameter Space in Electrical Unclonable Primitives.

Hardware security is not a new problem but is ever-growing in consumer and medical domains owing to hyperconnectivity. A physical unclonable function (PUF) offers a promising hardware security solution for cryptographic key generation, identification, and authentication. However, electrical PUFs using nanomaterials or two-dimensional (2D) transition metal dichalcogenides (TMDCs) often have limited entropy and parameter space sources, both of which increase the vulnerability to attacks and act as bottlenecks for practical applications. We report an electrical PUF with enhanced entropy as well as parameter space by incorporating 2D TMDC heteronanostructures into field-effect transistors (FETs). Lateral heteronanostructures of 2D molybdenum disulfide and tungsten disulfide serve as a potent entropy source. The variable feature of FETs is further leveraged to enhance the parameter space that provides multiple challenge-response pairs, which are essential for PUFs. This combination results in stably repeatable yet highly variable FET characteristics as alternative electrical PUFs. Comprehensive PUF performance analyses validate the bit uniformity, reproducibility, uniqueness, randomness, false rates, and encoding capacity. The 2D material heteronanostructure-driven electrical PUFs with strong FET-to-FET variability can potentially be augmented as an immediately deployable and scalable security solution for various hardware devices.

Rapid Self-Healing Hydrogel with Ultralow Electrical Hysteresis for Wearable Sensing.

Self-healing hydrogels are in high demand for wearable sensing applications due to their remarkable deformability, high ionic and electrical conductivity, self-adhesiveness to human skin, as well as resilience to both mechanical and electrical damage. However, these hydrogels face challenges such as delayed healing times and unavoidable electrical hysteresis, which limit their practical effectiveness. Here, we introduce a self-healing hydrogel that exhibits exceptionally rapid healing with a recovery time of less than 0.12 s and an ultralow electrical hysteresis of less than 0.64% under cyclic strains of up to 500%. This hydrogel strikes an ideal balance, without notable trade-offs, between properties such as softness, deformability, ionic and electrical conductivity, self-adhesiveness, response and recovery times, durability, overshoot behavior, and resistance to nonaxial deformations such as twisting, bending, and pressing. Owing to this unique combination of features, the hydrogel is highly suitable for long-term, durable use in wearable sensing applications, including monitoring body movements and electrophysiological activities on the skin.

A machine-learning-enabled smart neckband for monitoring dietary intake.

The increasing need for precise dietary monitoring across various health scenarios has led to innovations in wearable sensing technologies. However, continuously tracking food and fluid intake during daily activities can be complex. In this study, we present a machine-learning-powered smart neckband that features wireless connectivity and a comfortable, foldable design. Initially considered beneficial for managing conditions such as diabetes and obesity by facilitating dietary control, the device's utility extends beyond these applications. It has proved to be valuable for sports enthusiasts, individuals focused on diet control, and general health monitoring. Its wireless connectivity, ergonomic design, and advanced classification capabilities offer a promising solution for overcoming the limitations of traditional dietary tracking methods, highlighting its potential in personalized healthcare and wellness strategies.

mHealth hyperspectral learning for instantaneous spatiospectral imaging of hemodynamics.

Hyperspectral imaging acquires data in both the spatial and frequency domains to offer abundant physical or biological information. However, conventional hyperspectral imaging has intrinsic limitations of bulky instruments, slow data acquisition rate, and spatiospectral trade-off. Here we introduce hyperspectral learning for snapshot hyperspectral imaging in which sampled hyperspectral data in a small subarea are incorporated into a learning algorithm to recover the hypercube. Hyperspectral learning exploits the idea that a photograph is more than merely a picture and contains detailed spectral information. A small sampling of hyperspectral data enables spectrally informed learning to recover a hypercube from a red-green-blue (RGB) image without complete hyperspectral measurements. Hyperspectral learning is capable of recovering full spectroscopic resolution in the hypercube, comparable to high spectral resolutions of scientific spectrometers. Hyperspectral learning also enables ultrafast dynamic imaging, leveraging ultraslow video recording in an off-the-shelf smartphone, given that a video comprises a time series of multiple RGB images. To demonstrate its versatility, an experimental model of vascular development is used to extract hemodynamic parameters via statistical and deep learning approaches. Subsequently, the hemodynamics of peripheral microcirculation is assessed at an ultrafast temporal resolution up to a millisecond, using a conventional smartphone camera. This spectrally informed learning method is analogous to compressed sensing; however, it further allows for reliable hypercube recovery and key feature extractions with a transparent learning algorithm. This learning-powered snapshot hyperspectral imaging method yields high spectral and temporal resolutions and eliminates the spatiospectral trade-off, offering simple hardware requirements and potential applications of various machine learning techniques.

In Situ Spray Polymerization of Conductive Polymers for Personalized E-textiles.

E-textiles, also known as electronic textiles, seamlessly merge wearable technology with fabrics, offering comfort and unobtrusiveness and establishing a crucial role in health monitoring systems. In this field, the integration of custom sensor designs with conductive polymers into various fabric types, especially in large areas, has presented significant challenges. Here, we present an innovative additive patterning method that utilizes a dual-regime spray system, eliminating the need for masks and allowing for the programmable inscription of sensor arrays onto consumer textiles. Unlike traditional spray techniques, this approach enables in situ, on-the-fly polymerization of conductive polymers, enabling intricate designs with submillimeter resolution across fabric areas spanning several meters. Moreover, it addresses the nozzle clogging issues commonly encountered in such applications. The resulting e-textiles preserve essential fabric characteristics such as breathability, wearability, and washability while delivering exceptional sensing performance. A comprehensive investigation, combining experimental, computational, and theoretical approaches, was conducted to examine the critical factors influencing the operation of the dual-regime spraying system and its role in e-textile fabrication. These findings provide a flexible solution for producing e-textiles on consumer fabric items and hold significant implications for a diverse range of wearable sensing applications.

Revisiting silk: a lens-free optical physical unclonable function.

For modern security, devices, individuals, and communications require unprecedentedly unique identifiers and cryptographic keys. One emerging method for guaranteeing digital security is to take advantage of a physical unclonable function. Surprisingly, native silk, which has been commonly utilized in everyday life as textiles, can be applied as a unique tag material, thereby removing the necessary apparatus for optical physical unclonable functions, such as an objective lens or a coherent light source. Randomly distributed fibers in silk generate spatially chaotic diffractions, forming self-focused spots on the millimeter scale. The silk-based physical unclonable function has a self-focusing, low-cost, and eco-friendly feature without relying on pre-/post-process for security tag creation. Using these properties, we implement a lens-free, optical, and portable physical unclonable function with silk identification cards and study its characteristics and reliability in a systemic manner. We further demonstrate the feasibility of the physical unclonable functions in two modes: authentication and data encryption.

Edible Matrix Code with Photogenic Silk Proteins.

Counterfeit medicines are a healthcare security problem, posing not only a direct threat to patient safety and public health but also causing heavy economic losses. Current anticounterfeiting methods are limited due to the toxicity of the constituent materials and the focus of secondary packaging level protections. We introduce an edible, imperceptible, and scalable matrix code of information representation and data storage for pharmaceutical products. This matrix code is digestible as it is composed of silk fibroin genetically encoded with fluorescent proteins produced by ecofriendly, sustainable silkworm farming. Three distinct fluorescence emission colors are incorporated into a multidimensional parameter space with a variable encoding capacity in a format of matrix arrays. This code is smartphone-readable to extract a digitized security key augmented by a deep neural network for overcoming fabrication imperfections and a cryptographic hash function for enhanced security. The biocompatibility, photostability, thermal stability, long-term reliability, and low bit error ratio of the code support the immediate feasibility for dosage-level anticounterfeit measures and authentication features. The edible code affixed to each medicine can serve as serialization, track and trace, and authentication at the dosage level, empowering every patient to play a role in combating illicit pharmaceuticals.

Biodegradable silicon nanoneedles for ocular drug delivery.

Ocular drug delivery remains a grand challenge due to the complex structure of the eye. Here, we introduce a unique platform of ocular drug delivery through the integration of silicon nanoneedles with a tear-soluble contact lens. The silicon nanoneedles can penetrate into the cornea in a minimally invasive manner and then undergo gradual degradation over the course of months, enabling painless and long-term sustained delivery of ocular drugs. The tear-soluble contact lens can fit a variety of corneal sizes and then quickly dissolve in tear fluid within a minute, enabling an initial burst release of anti-inflammatory drugs. We demonstrated the utility of this platform in effectively treating a chronic ocular disease, such as corneal neovascularization, in a rabbit model without showing a notable side effect over current standard therapies. This platform could also be useful in treating other chronic ocular diseases.

Graphene-on-silver substrates for sensitive surface plasmon resonance imaging biosensors.

Taking advantage of the high impermeability property of graphene and the sharp surface plasmon resonance (SPR) curve of silver, we numerically demonstrate that SPR imaging biosensors with a graphene-on-silver substrate can be used to achieve the dramatically high sensitivity as well as to prevent silver oxidation. Results of our numerical study show that a silver substrate with a few graphene layers can significantly increase the imaging sensitivity, compared to the conventional gold-film-based SPR imaging biosensor. In particular, single layered graphene deposited on the 60-nm thick silver film amplifies the SPR imaging signal more than three times. Therefore, the proposed SPR substrate could potentially open a new possibility of SPR imaging detection for sensitive and high-throughput assessment of multiple biomolecular interactions.

Random laser spectroscopy for nanoscale perturbation sensing.

We report a spectroscopic method using coherent random lasers for a simple, yet nanoscale, sensing approach. Unique spectral properties of coherent random laser emission can be detectably altered when introducing nanoscale perturbations to a simple nanocomposite film that consists of dielectric nanospheres and laser-dye-doped polymer to serve as a transducer. Random lasing action provides a means to amplify subtle perturbations to readily detectable spectral shifts in multiple discrete emission peaks. Owing to several advantages, such as large-area detection, narrow and multiple emission peaks, straightforward detection, and simple fabrication, random laser spectroscopy has the potential for ultrasensitive, yet simple, biosensors in various applications.

Random lasing in bone tissue.

Owing to the low-loss and high refractive index variations derived from the basic building block of bone structure, we, for the first time to our knowledge, demonstrate coherent random lasing action originated from the bone structure infiltrated with laser dye, revealing that bone tissue is an ideal biological material for random lasing. Our numerical simulation shows that random lasers are extremely sensitive to subtle structural changes even at nanoscales and can potentially be an excellent tool for probing nanoscale structural alterations in real time as a novel spectroscopic modality.