Biomedical Imaging Applications Research Articles

Polarization‐Sensitive and Self‐Driven Pyro‐Phototronic Photodetectors Based on MoS2‐Water Heterojunctions

AbstractPolarization‐sensitive and self‐driven pyroelectric‐based photodetectors have recently gained interest due to their potential application in artificial electronic eyes, biomedical imaging, and optical switches. Here, a photodetector based on light modulation‐induced polarization and depolarization of water molecules on the surface of a 2D MoS2 crystal is reported. The MoS2‐water heterostructure photodetector serves as a self‐driven pyro‐phototronic device that converts light‐induced thermal energy to electrical signals, leading to a transient photoresponsivity as high as 24.6 mA W−1 and a specific detectivity of 2.85 × 108 Jones under 470 nm wavelength at zero bias. Due to the formation of a built‐in electric field at the MoS2‐water interface, this structure also has a high steady–state responsivity of 3.62 A W−1 and detectivity of 9.18 × 108 Jones at 3 V bias, along with a fast response time of ≈0.74 ms. Moreover, due to the rearrangement of the hydrogen bond network in the liquid water upon visible light illumination, the MoS2‐water photodetector is light polarization‐sensitive. The simple fabrication process, low cost, polarization sensitivity, and high performance of the MoS2‐water structure make it an excellent candidate for liquid‐compatible photodetectors.

An intelligent neural network model to detect red blood cells for various blood structure classification in microscopic medical images

Biomedical image analysis plays a crucial role in enabling high-performing imaging and various clinical applications. For the proper diagnosis of blood diseases related to red blood cells, red blood cells must be accurately identified and categorized. Manual analysis is time-consuming and prone to mistakes. Analyzing multi-label samples, which contain clusters of cells, is challenging due to difficulties in separating individual cells, such as touching or overlapping cells. High-performance biomedical imaging and several medical applications are made possible by advanced biosensors. We develop an intelligent neural network model that can automatically identify and categorize red blood cells from microscopic medical images using region-based convolutional neural networks (RCNN) and cutting-edge biosensors. Our model successfully navigates obstacles like touching or overlapping cells and accurately recognizes various blood structures. Additionally, we utilized data augmentation as a pre-processing method on microscopic images to enhance the model's computational efficiency and expand the sample size. To refine the data and eliminate noise from the dataset, we utilized the Radial Gradient Index filtering algorithm for imaging data equalization. We exhibit improved detection accuracy and a reduced model loss rate when using medical imagery datasets to apply our proposed model in comparison to existing ResNet and GoogleNet models. Our model precisely detected red blood cells in a collection of medical images with 99% training accuracy and 91.21% testing accuracy. Our proposed model outperformed earlier models like ResNet-50 and GoogleNet by 10-15%. Our results demonstrated that Artificial intelligence (AI)-assisted automated red blood cell detection has the potential to revolutionize and speed up blood cell analysis, minimizing human error and enabling early illness diagnosis.

A Method to Obtain the Transducers Impulse Response (TIR) in Photoacoustic Imaging

Photoacoustic tomography (PAT) is an emerging imaging technique with great potential for a wide range of biomedical imaging applications. The transducers impulse response (TIR) is a key factor affecting the performance of photoacoustic imaging (PAI). It is customary in PAI to assume that TIR is known or obtain it from experiments. In this paper, we investigate the possibility of obtaining TIR in another way. A new method is proposed to extract TIR from observed optoacoustic signal (OPAS) data, without prior knowledge, as a known condition. It is based on the relation between the OPAS data and the photoacoustic pressure signal (PAPS) at transducer positions. The relation can be expressed as a homogeneous linear equation. The TIR is solved by solving the homogeneous equation. The numerical test verifies the effectiveness of the presented method. This article also discusses the effect of calculation parameters on the extracting precision of TIR.

Frequency selection rule for the HDHF Lissajous scanning imaging with a low-voltage one axis actuated PZT scanner based on an asymmetric fiber cantilever.

Lissajous micro scanners are very attractive in compact laser scanning applications for biomedical endoscopic imaging, such as confocal microscopy, endomicroscopy or optical coherence tomography. The scanning frequencies have a very important effect on the quality of the resulting Lissajous scanning imaging. In this paper, we propose a frequency selection rule for high definition and high frame-rate (HDHF) Lissajous scanning imaging, by deriving the relationship among the scanning field of view (FOV), actuation frequencies and pixel size based on the characteristics of the scanning trajectory. The minimum sampling rate based on the proposed frequency selection rule is further discussed. We report a lead zirconate titanate piezoelectric ceramic (PZT) based Lissajous fiber scanner to achieve HDHF Lissajous scanning imaging. Based on the frequency selection rule, different frequency combinations are calculated, under which the Lissajous fiber scanner can work at the frame rate (FR) of 10 Hz, 20 Hz, 40 Hz and 52 Hz. The trajectory evolution of the Lissajous scanning at the frame rate of 10 Hz has been obtained to verify the applicability of the proposed rule. The measured resolution of the scanner is 50.8 lp/mm at the unit optical magnification, and the measured FOV at the FR of 10 Hz and 40 Hz are 1.620 mm ×1.095 mm and 0.405 mm ×0.27 mm, respectively. HDHF Lissajous scanning images of the customized spatial varying binary pattern are obtained and reconstructed at the FR of 10 Hz and 40 Hz, demonstrating the practicability of the frequency selection rule.

Awakening the Dumb Site to Realize Ultra‐Broadband NIR Phosphor

AbstractNear‐infrared (NIR) light sources have gained immense popularity in recent years due to their wide range of applications in various fields, including spectroscopy and biomedical imaging. However, the limited emission bandwidth of NIR phosphors is a significant bottleneck in their development. Here, a novel strategy is reported to broaden the emission bandwidth of NIR phosphors by awakening the dumb site. Na4M3Ta(PO4)6: Cr3+ (M = Al3+, Ga3+, In3+) phosphor is synthesized, which exhibits a greatly broadened bandwidth from 134 to 232 nm. Structural and spectral analysis reveals that the NaO6 octahedral site has a severe t2g‐type distortion, making it a dumb site for Cr3+. By introducing larger In3+ at the M site, the angular distortion at the NaO6 site decreases to the normal range, enabling the luminescence of Cr3+ again. Along with the broadened bandwidth, the emission peak also redshifts from 802 to 977 nm, giving advantages in NIR spectroscopy applications. Interestingly, the awakened luminescence at the NaO6 site shows even better luminescence properties than the original M/TaO6 octahedral site. These findings reveal a novel insight into the luminescence of Cr3+ at the octahedral site, which could potentially revolutionize the design of NIR phosphors.

Full-color peptide-based fluorescent nanomaterials assembled under the control of amino acid doping.

Peptide-based biofluorescents are of great interest due to their controllability and biocompatibility, as well as their potential applications in biomedical imaging and biosensing. Here, we present a simple approach to synthesizing full-color fluorescent nanomaterials with broad-spectrum fluorescence emissions, high optical stability, and long fluorescence lifetimes. By doping amino acids during the enzyme-catalyzed oxidative self-assembly of tyrosine-based peptides, we can precisely control the intermolecular interactions to obtain nanoparticles with fluorescence emission at different wavelengths. The synthesized peptide-based fluorescent nanomaterials with excellent biocompatibility and stable near-infrared fluorescence emission were shown to have potential for bioimaging applications. This research provides new ideas for the development of new bioluminescent materials that are cost-effective, environmentally friendly, and safe for biomedical use.

Low voltage-driven, high-performance TiO2 thin film transistors with MHz switching speed.

High-speed circuits based on thin film transistors (TFTs) show promising potential applications in biomedical imaging and human-machine interactions. One of the critical requirements for high-speed electronic devices lies in high-frequency switching or amplification at low voltages, typically driven by batteries (∼3.0 V). To date, however, most electrical performances of metal oxide TFTs are measured under direct current (DC) conditions, and their dynamic switching behaviour is scarcely explored and studied systematically. Here in this work, we present low voltage-driven, high-performance TiO2 thin film transistors, which can be operated at a switching speed of MHz. Our proposed TiO2 TFTs demonstrated a high on-off ratio of 107, together with a subthreshold swing (SS) of ∼150 mV Dec-1 averaged over four orders of magnitude, which can be further reduced below 100 mV Dec-1 when the temperature cools to 77 K. Additionally, the TiO2 TFTs exhibit excellent gate-pulse switching at various frequencies ranging from 1.0 Hz to 1.0 MHz. We also explored the potential application of the TiO2 TFTs as logic gates by constructing a resistive-loaded inverter, which shows stable operation at 10 kHz frequency and various temperatures. Thus, our results show the great potential of TiO2 TFTs as a new platform for high-speed electronic applications.

Multi-functional GdEuxTb1-xO3 (x = 0 to 1) nanoparticles: colour tuning optical properties, water proton spin relaxivities, and X-ray attenuation properties.

Multi-functional nanoparticles are useful for various applications, such as biomedical imaging, detection, and display technologies. Colour-tunable GdEuxTb1-xO3 nanoparticles were synthesized with emission colour ranging from green (545 nm) to red (616 nm) by varying x (x = 0, 0.1, 0.3, 0.5, 0.7, 0.9, and 1). These nanoparticles were surface-grafted with polyacrylic acid and a small quantity of 2,6-pyridinedicarboxylic acid. This modification aimed to ensure long-term colloidal stability (>1 year without precipitation) and high quantum yields (>30%) in aqueous media. Additionally, they exhibited long emission lifetimes (∼1 ms), high longitudinal water proton spin relaxivities (>30 s-1mM-1), and high X-ray attenuation efficiencies (∼10 HU mM-1). These multiple exceptional properties within a single nanoparticle make them highly valuable for applications in biomedical imaging, noise-free signal detection, and colour display.

On transient absorption and dual emission of the atomically precise, DNA-stabilized silver nanocluster Ag16Cl2.

DNA-stabilized silver nanoclusters with 10 to 30 silver atoms are interesting biocompatible nanomaterials with intriguing fluorescence properties. However, they are not well understood, since atom-scale high level theoretical calculations have not been possible due to a lack of firm experimental structural information. Here, by using density functional theory (DFT), we study the recently atomically resolved (DNA)2-Ag16Cl2 nanocluster in solvent under the lowest-lying singlet (S1) and triplet (T1) excited states, estimate the relative emission maxima for the allowed (S1 → S0) and dark (T1 → S0) transitions, and evaluate the transient absorption spectra. Our results offer a potential interpretation of the recently reported transient absorption and dual emission of similar DNA-stabilized silver nanoclusters, providing a mechanistic view on their photophysical properties that are attractive for applications in biomedical imaging and biophotonics.

Piezoelectric PVDF and its copolymers in biomedicine: innovations and applications.

In recent years, poly(vinylidene fluoride) (PVDF) has emerged as a versatile polymer with a wide range of applications across various fields. PVDF's piezosensitivity, versatility, crystalline structure, and tunable parameters have established it as a highly sought-after material. Furthermore, PVDF and its copolymers exhibit excellent processability and chemical resistance to a diverse array of substances. Of particular significance is its remarkable structural stability in physiological media, which highlights its potential for use in the development of biomedical products. This review offers a comprehensive overview of the latest advancements in PVDF-based biomedical systems. It examines the fabrication of stimulus-responsive delivery systems, bioelectric therapy devices, and tissue-regenerating scaffolds, all of which harness the piezosensitivity of PVDF. Moreover, the potential of PVDF in the fabrication of both invasive and non-invasive diagnostic tools is investigated, with particular emphasis on its flexibility, transparency, and piezoelectric efficiency. The material's high biocompatibility and physiological stability are of paramount importance in the development of implantable sensors for long-term health monitoring, which is crucial for the management of chronic diseases and postoperative care. Additionally,we discuss a novel approach to photoacoustic microscopy that employs a PVDF sensor, thereby eliminating the necessity for external contrast agents. This technique provides a new avenue for non-invasive imaging in biomedical applications. Finally, we explore the challenges and prospects for the development of PVDF-based systems for a range of biomedical applications. This review is distinctive in comparison to other reviews on PVDF due to its concentrated examination of biomedical applications, including pioneering imaging techniques, long-term health monitoring, and a detailed account of advancements in the field. Collectively, these elements illustrate the potential of PVDF to markedly influence biomedical engineering and patient care, distinguishing it from existing literature. By leveraging the distinctive attributes of PVDF and its copolymers, researchers can continue to advance the frontiers of biomedical engineering, with the potential to transform patient care and treatment outcomes.

Broadband short-wave infrared Mg4Nb2O9:Cr3+,Li+ phosphor for nondestructive safety detection and biomedical imaging

Blue-excitable broadband short-wave infrared Mg4Nb2O9: 3%Cr3+,Li+ phosphors with high crystallinity and enhanced emission were innovatively developed for pc-LED applications in nondestructive safety detection, biomedical imaging, and other fields.

Optimization of a nanoparticle uptake protocol applied to amniotic-derived cells: unlocking the therapeutic potential.

Stem cell-based therapy implementation relies heavily on advancements in cell tracking. The present research has been designed to develop a gold nanorod (AuNR) labeling protocol applied to amniotic epithelial cells (AECs) leveraging the pro-regenerative properties of this placental stem cell source which is widely used for both human and veterinary biomedical regenerative applications, although not yet exploited with tracking technologies. Ovine AECs, in native or induced mesenchymal (mAECs) phenotypes via epithelial-mesenchymal transition (EMT), served as the model. Initially, various uptake methods validated on other sources of mesenchymal stromal cells (MSCs) were assessed on mAECs before optimization for AECs. Furthermore, the protocol was implemented by adopting the biological strategy of MitoCeption to improve endocytosis. The results indicate that the most efficient, affordable, and easy protocol leading to internalization of AuNRs in living mAECs recognized the combination of the one-step uptake condition (cell in suspension), centrifugation-mediated internalization method (G-force) and MitoCeption (mitochondrial isolated from mAECs). This protocol produced labeled vital mAECs within minutes, suitable for preclinical and clinical trials. The optimized protocol has the potential to yield feasible labeled amniotic-derived cells for biomedical purposes: up to 10 million starting from a single amniotic membrane. Similar and even higher efficiency was found when the protocol was applied to ovine and human AECs, thereby demonstrating the transferability of the method to cells of different phenotypes and species-specificity, hence validating its great potential for the development of improved biomedical applications in cell-based therapy and diagnostic imaging.

Plasmon-enhanced optoacoustic transducer with Ecoflex thin film for broadband ultrasound generation using overdriven pulsed laser diode.

Ultrasonic transducers facilitate noninvasive biomedical imaging and therapeutic applications. Optoacoustic generation using nanoplasmonic structures provides a technical solution for highly efficient broadband ultrasonic transducer. However, bulky and high-cost nanosecond lasers as conventional excitation sources hinder a compact configuration of transducer. Here, we report a plasmon-enhanced optoacoustic transducer (PEAT) for broadband ultrasound generation, featuring an overdriven pulsed laser diode (LD) and an Ecoflex thin film. The PEAT module consists of an LD, a collimating lens, a focusing lens, and an Ecoflex-coated 3D nanoplasmonic substrate (NPS). The LD is overdriven above its nominal current and precisely modulated to achieve nanosecond pulsed beam with high optical peak power. The focused laser beam is injected on the NPS with high-density electromagnetic hotspots, which allows for the efficient plasmonic photothermal effect. The thermal expansion of Ecoflex finally generates broadband ultrasound. The overdriven pulsed LD achieves a maximum optical peak power of 40W, exceeding the average optical power of 3W. The thick Ecoflex-coated NPS exhibits an eightfold optoacoustic enhancement with a fractional bandwidth higher than 160% and a peak frequency of 2.5MHz. In addition, the optoacoustic amplitude is precisely controlled by the optical peak power or the laser pulse width. The PEAT-integrated microfluidic chip clearly demonstrates acoustic atomization by generating aerosol droplets at the air-liquid interface. Plasmon-enhanced optoacoustic generation using PEAT can provide an approach for compact and on-demand biomedical applications, such as ultrasound imaging and lab-on-a-chip technologies.

Metalens array miniaturized microscope for large-field-of-view imaging

Miniaturized microscopes with large field-of-view (FOV) have wide applications in biomedical imaging and automated machine vision. Conventional microscopes with a single objective lens have tradeoffs among FOV, resolution and device thickness. Thanks to the high compactness and design flexibility, metalens has a great potential for building the next generation compact imagers. However, there have been various challenges and performance tradeoffs in the design, fabrication and implementation of metalens that could support a large FOV. Here, we present a metalens array based miniaturized microscope that provides extremely high compactness and large FOV. Each metalens unit can image the object tile immediately below it. By tiling such metalens units, we can scale up the FOV while keeping the same device thickness and imaging quality as the microscope with a single metalens unit. Our metalens array enables a compact microscope that can perform large FOV imaging through arbitrary polarized light. We experimentally demonstrated the miniaturized metalens array microscope in 1310 nm wavelength, which has an FOV of 3 × 4 mm2 and can resolve 6.9 μm lines, with 4 mm distance between the sample surface to the camera sensor. Although this is a proof-of-concept demonstration, our metalens array microscope provides a promising solution for portable and implantable camera for large-FOV high-resolution imaging.

Ultrathin film optical coatings for all-optical mathematical operations with ultrahigh numerical aperture

Optical analog computation is garnering increasing attention due to its innate parallel processing capabilities, swift computational speeds, and minimal energy requirements. However, traditional optical components employed for such computations are usually bulky. Recently, there has been a substantial shift toward utilizing nanophotonic structures to downsize these bulky optical elements. Nevertheless, these nanophotonic structures are typically realized in planar subwavelength nanostructures, demanding intricate fabrication processes and presenting limitations in their numerical apertures. In this study, we present a three-layer thin-film optical coating different from the conventional Fabry–Pérot nanocavity. Our design functions as a real-time Laplacian operator for spatial differentiation, and it remarkably boasts an ultrahigh numerical aperture of up to 0.7, enabling the detected edges to be sharper and have closely matched intensities. We also experimentally demonstrate its capacity for effective edge detection. This ultracompact and facile-to-fabricate thin-film spatial differentiator holds promising prospects for applications in ultrafast optical processing and biomedical imaging.

Synthesis of Thiazoloindole α-Amino Acids: Chromophores Amenable to One- and Two-Photon Induced Fluorescence.

Thiazoloindole α-amino acids have been synthesized in four steps from tryptophan using a dual-catalytic thiolation reaction and a copper-mediated intramolecular N-arylation process. Late-stage diversification of the thiazoloindole core with electron-deficient aryl substituents produced chromophores that on one-photon excitation displayed blue-green emission, mega-Stokes shifts, and high quantum yields. The thiazoloindole amino acids could also be excited via two-photon absorption in the near-infrared, demonstrating their potential for biomedical imaging applications.

Solution‐Processed Ternary Organic Photodetectors with Ambipolar Small‐Bandgap Polymer for Near‐Infrared Sensing

AbstractOrganic photodetectors (OPDs) detecting light in the near‐infrared (NIR) range from 900 to 1200 nm offer numerous applications in biomedical imaging and health monitoring. However, an ultra‐low bandgap of the electron donor compound required to achieve NIR detection poses a unique challenge in selecting a complementary acceptor material with a suitable energy‐level offset. To tackle this, a solution‐processed, fullerene‐dominated, ternary device is engineered by adding an ultra‐low bandgap (0.6–0.8 eV) ambipolar polymer, polybenzobisthiadiazole‐dithienocyclopentane (PBBTCD), into the active layer of visible‐light‐responsive OPDs (bandgap of 1.8 eV) to form a ternary blend. The resulting OPD benefits from the extended absorption beyond 1000 nm. The cascaded energy level alignment within the ternary blend and the applied reverse bias both improve the overall NIR photocurrent responsivity by 2 orders of magnitude, reaching 0.4 mA W−1 at 1050 nm and −2 V for ternary devices. Furthermore, a photovoltage responsivity of 0.3 mV m2 W−1 along with significant open‐circuit voltage (Voc) of 0.12 V allow NIR detection in the Voc mode. Prominently, this ability is accomplished with a minimal presence of PBBTCD. Taken together, this work indicates potential strategies for extending the spectral activity of conventional OPDs through introduction of an ambipolar ultra‐low bandgap polymer as a minor element.

Volumetric photoacoustic imaging with symmetric spatial resolution in transverse plane from the asymmetric array using a virtual-transducer concept

Volumetric photoacoustic imaging based on the one-dimensional array has shown increasing applications for its low cost and convenient integration. However, due to the asymmetric angular detection aperture, the image obtained from such arrays faces challenges of asymmetric spatial resolution and artifacts. To address these issues, a virtual-transducer-based approach is proposed to achieve a volumetric image with symmetric resolution and low artifacts. By considering the asymmetric array as a symmetrical spherical-focused virtual transducer, the method ensures a symmetric angular detection aperture. The entire image reconstruction is then based on the equivalent symmetric data. Simulation and phantom experiment demonstrate excellent symmetric resolution and low artifact performance. The ratio of the average intensity between targets and artifacts is suppressed up to 25.09 dB. The in vivo experiment validates the biomedical practicability of the proposed method. This approach exhibits a general value and holds significant promise for low-cost, convenient, and high-quality volumetric photoacoustic imaging in biomedical applications.

Insights on salting-out triggering aggregation-induced emission in nitrogen-doped graphene quantum dots

A straightforward methodology for obtaining Nitrogen-doped Graphene Quantum Dots (N-GQDs) with aggregation-induced emission (AIE) using salting-out purification processes is presented in this work. Various salts, including NaCl at concentrations of 50 mM, were found to be effective for stratification of graphene-based materials (GBMs) by salting-out treatments. These salts were shown to be safer, more cost-effective, and environmentally sustainable alternatives to (NH4)2SO4 reported in previous works. Remarkably, this method demonstrated the ability to promote the self-assembly of N-GQDs into stable J-aggregates-like arrays with an average fluorescence decay time of ca. 4 ns and absolute quantum yield with values of 3.5 % and 6.9 % for 100 mM and 2 M, respectively. In contrast to a typical quenching effect caused by π-stacking, these arrays exhibited aggregation-induced emissions, as evidenced by the presence of new excitation and emission bands at 532 and 600 nm, respectively. The scalability of the process, along with the absence of additional purification steps, renders these results of great scientific and technological interest. Furthermore, the modulable fluorescence, size, and stability of these GBMs suggest their potential application in energy cells, sensors, and biomedical imaging.

Fast physic-informed mixer architecture for color Lensfree holographic reconstruction

Accurate color image reconstruction from multi-wavelength holograms is crucial in biomedical imaging applications. Current data-driven deep learning methods have made significant progress with promising reconstruction performance. Especially, untrained neural network methods have been developed to overcome data acquisition and the generalization issue. However, improving reconstruction quality requires more iterations, which can lead to longer convergence time. To address this challenge, we proposed an efficient complex-valued attention mixer (ECA-Mixer) architecture for fast and accurate physic-informed color holographic reconstruction. Our architecture consists of three core modules, an encoder, a nonlinear transformer and a decoder, each combining efficient attention mechanisms and Mixer layers for channel feature extraction and spatial information transformation. To preserve high-frequency information, we also introduced the use of 2D Haar wavelet and its inverse transform for encoding and decoding features. We then validate our method with extensive experiments on simulated and experimental samples and achieve state-of-art color reconstruction results in terms of computation time and image quality. Besides, we also demonstrate that our proposed lightweight network is capable of imaging large-size wide-field samples at a higher resolution in just a few minutes. The code is available and will be uploaded later at https://github.com/DeepPhysicVision/ECA-Mixer.git.