Multimodal, Multifunctional Biosensors or Imaging Systems and Their Biomedical Applications

A special issue of Biosensors (ISSN 2079-6374). This special issue belongs to the section "Biosensors and Healthcare".

Deadline for manuscript submissions: closed (24 December 2022) | Viewed by 43147

Special Issue Editor

Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli 350, Taiwan
Interests: neurophotonics; biosensors; neuroengineering; brain-computer interface; experimental neuroscience

Special Issue Information

Dear Colleagues,

To investigate the dynamics of biological processes, it is necessary to have technology which can capture the various states from the biological system. One or more biosensors or imaging systems can be of help to further reveal their real states. That is, the importance of using multimodal and multifunctional biosensing and bioimaging techniques has grown intensively within the last few decades, especially the use of those techniques for direct or indirect visualization of biological tissues. We aim to publish high-quality research and review papers related to different biosensors or imaging systems and their biomedical applications, which help toward better understanding biological processes and apply biosensor methods in experimental or biomedical engineering or even clinical medicine. It will not only be exciting but also of great benefit to the scientific society to discuss recent developments and improvements in these biosensors or imaging systems.

Dr. Lun-De Liao
Guest Editor

Manuscript Submission Information

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Keywords

  • biosensors
  • cell-based sensors
  • optical-based sensors
  • wearable sensors
  • real-time monitoring
  • drug screening
  • biomedical optical imaging (voltage-sensitive dye imaging, photoacoustic microscopy, optical coherence tomography, near-infrared microscopy, hybrid imaging methods)
  • ex vivo or in vivo applications
  • biosensors in clinical applications

Published Papers (14 papers)

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Research

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19 pages, 7968 KiB  
Article
Upper-Arm Photoplethysmographic Sensor with One-Time Calibration for Long-Term Blood Pressure Monitoring
by Ching-Fu Wang, Ting-Yun Wang, Pei-Hsin Kuo, Han-Lin Wang, Shih-Zhang Li, Chia-Ming Lin, Shih-Chieh Chan, Tzu-Yu Liu, Yu-Chun Lo, Sheng-Huang Lin and You-Yin Chen
Biosensors 2023, 13(3), 321; https://doi.org/10.3390/bios13030321 - 25 Feb 2023
Cited by 3 | Viewed by 2805
Abstract
Wearable cuffless photoplethysmographic blood pressure monitors have garnered widespread attention in recent years; however, the long-term performance values of these devices are questionable. Most cuffless blood pressure monitors require initial baseline calibration and regular recalibrations with a cuffed blood pressure monitor to ensure [...] Read more.
Wearable cuffless photoplethysmographic blood pressure monitors have garnered widespread attention in recent years; however, the long-term performance values of these devices are questionable. Most cuffless blood pressure monitors require initial baseline calibration and regular recalibrations with a cuffed blood pressure monitor to ensure accurate blood pressure estimation, and their estimation accuracy may vary over time if left uncalibrated. Therefore, this study assessed the accuracy and long-term performance of an upper-arm, cuffless photoplethysmographic blood pressure monitor according to the ISO 81060-2 standard. This device was based on a nonlinear machine-learning model architecture with a fine-tuning optimized method. The blood pressure measurement protocol followed a validation procedure according to the standard, with an additional four weekly blood pressure measurements over a 1-month period, to assess the long-term performance values of the upper-arm, cuffless photoplethysmographic blood pressure monitor. The results showed that the photoplethysmographic signals obtained from the upper arm had better qualities when compared with those measured from the wrist. When compared with the cuffed blood pressure monitor, the means ± standard deviations of the difference in BP at week 1 (baseline) were −1.36 ± 7.24 and −2.11 ± 5.71 mmHg for systolic and diastolic blood pressure, respectively, which met the first criterion of ≤5 ± ≤8.0 mmHg and met the second criterion of a systolic blood pressure ≤ 6.89 mmHg and a diastolic blood pressure ≤ 6.84 mmHg. The differences in the uncalibrated blood pressure values between the test and reference blood pressure monitors measured from week 2 to week 5 remained stable and met both criteria 1 and 2 of the ISO 81060-2 standard. The upper-arm, cuffless photoplethysmographic blood pressure monitor in this study generated high-quality photoplethysmographic signals with satisfactory accuracy at both initial calibration and 1-month follow-ups. This device could be a convenient and practical tool to continuously measure blood pressure over long periods of time. Full article
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19 pages, 2692 KiB  
Article
Proof of Concept for Sustainable Manufacturing of Neural Electrode Array for In Vivo Recording
by Szu-Ying Li, Hsin-Yi Tseng, Bo-Wei Chen, Yu-Chun Lo, Huai-Hsuan Shao, Yen-Ting Wu, Ssu-Ju Li, Ching-Wen Chang, Ta-Chung Liu, Fu-Yu Hsieh, Yi Yang, Yan-Bo Lai, Po-Chun Chen and You-Yin Chen
Biosensors 2023, 13(2), 280; https://doi.org/10.3390/bios13020280 - 16 Feb 2023
Viewed by 2426
Abstract
Increasing requirements for neural implantation are helping to expand our understanding of nervous systems and generate new developmental approaches. It is thanks to advanced semiconductor technologies that we can achieve the high-density complementary metal-oxide-semiconductor electrode array for the improvement of the quantity and [...] Read more.
Increasing requirements for neural implantation are helping to expand our understanding of nervous systems and generate new developmental approaches. It is thanks to advanced semiconductor technologies that we can achieve the high-density complementary metal-oxide-semiconductor electrode array for the improvement of the quantity and quality of neural recordings. Although the microfabricated neural implantable device holds much promise in the biosensing field, there are some significant technological challenges. The most advanced neural implantable device relies on complex semiconductor manufacturing processes, which are required for the use of expensive masks and specific clean room facilities. In addition, these processes based on a conventional photolithography technique are suitable for mass production, which is not applicable for custom-made manufacturing in response to individual experimental requirements. The microfabricated complexity of the implantable neural device is increasing, as is the associated energy consumption, and corresponding emissions of carbon dioxide and other greenhouse gases, resulting in environmental deterioration. Herein, we developed a fabless fabricated process for a neural electrode array that was simple, fast, sustainable, and customizable. An effective strategy to produce conductive patterns as the redistribution layers (RDLs) includes implementing microelectrodes, traces, and bonding pads onto the polyimide (PI) substrate by laser micromachining techniques combined with the drop coating of the silver glue to stack the laser grooving lines. The process of electroplating platinum on the RDLs was performed to increase corresponding conductivity. Sequentially, Parylene C was deposited onto the PI substrate to form the insulation layer for the protection of inner RDLs. Following the deposition of Parylene C, the via holes over microelectrodes and the corresponding probe shape of the neural electrode array was also etched by laser micromachining. To increase the neural recording capability, three-dimensional microelectrodes with a high surface area were formed by electroplating gold. Our eco-electrode array showed reliable electrical characteristics of impedance under harsh cyclic bending conditions of over 90 degrees. For in vivo application, our flexible neural electrode array demonstrated more stable and higher neural recording quality and better biocompatibility as well during the 2-week implantation compared with those of the silicon-based neural electrode array. In this study, our proposed eco-manufacturing process for fabricating the neural electrode array reduced 63 times of carbon emissions compared to the traditional semiconductor manufacturing process and provided freedom in the customized design of the implantable electronic devices as well. Full article
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21 pages, 6066 KiB  
Article
Experimental Verification for Numerical Simulation of Thalamic Stimulation-Evoked Calcium-Sensitive Fluorescence and Electrophysiology with Self-Assembled Multifunctional Optrode
by Yao-Wen Liang, Ming-Liang Lai, Feng-Mao Chiu, Hsin-Yi Tseng, Yu-Chun Lo, Ssu-Ju Li, Ching-Wen Chang, Po-Chuan Chen and You-Yin Chen
Biosensors 2023, 13(2), 265; https://doi.org/10.3390/bios13020265 - 13 Feb 2023
Cited by 1 | Viewed by 2322
Abstract
Owing to its capacity to eliminate a long-standing methodological limitation, fiber photometry can assist research gaining novel insight into neural systems. Fiber photometry can reveal artifact-free neural activity under deep brain stimulation (DBS). Although evoking neural potential with DBS is an effective method [...] Read more.
Owing to its capacity to eliminate a long-standing methodological limitation, fiber photometry can assist research gaining novel insight into neural systems. Fiber photometry can reveal artifact-free neural activity under deep brain stimulation (DBS). Although evoking neural potential with DBS is an effective method for mediating neural activity and neural function, the relationship between DBS-evoked neural Ca2+ change and DBS-evoked neural electrophysiology remains unknown. Therefore, in this study, a self-assembled optrode was demonstrated as a DBS stimulator and an optical biosensor capable of concurrently recording Ca2+ fluorescence and electrophysiological signals. Before the in vivo experiment, the volume of tissue activated (VTA) was estimated, and the simulated Ca2+ signals were presented using Monte Carlo (MC) simulation to approach the realistic in vivo environment. When VTA and the simulated Ca2+ signals were combined, the distribution of simulated Ca2+ fluorescence signals matched the VTA region. In addition, the in vivo experiment revealed a correlation between the local field potential (LFP) and the Ca2+ fluorescence signal in the evoked region, revealing the relationship between electrophysiology and the performance of neural Ca2+ concentration behavior. Concurrent with the VTA volume, simulated Ca2+ intensity, and the in vivo experiment, these data suggested that the behavior of neural electrophysiology was consistent with the phenomenon of Ca2+ influx to neurons. Full article
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22 pages, 5003 KiB  
Article
Visible CCD Camera-Guided Photoacoustic Imaging System for Precise Navigation during Functional Rat Brain Imaging
by Yuhling Wang, Yu-Lin Chen, Chih-Mao Huang, Li-Tzong Chen and Lun-De Liao
Biosensors 2023, 13(1), 107; https://doi.org/10.3390/bios13010107 - 06 Jan 2023
Cited by 2 | Viewed by 1844
Abstract
In photoacoustic (PA) imaging, tissue absorbs specific wavelengths of light. The absorbed energy results in thermal expansion that generates ultrasound waves that are reconstructed into images. Existing commercial PA imaging systems for preclinical brain imaging are limited by imprecise positioning capabilities and inflexible [...] Read more.
In photoacoustic (PA) imaging, tissue absorbs specific wavelengths of light. The absorbed energy results in thermal expansion that generates ultrasound waves that are reconstructed into images. Existing commercial PA imaging systems for preclinical brain imaging are limited by imprecise positioning capabilities and inflexible user interfaces. We introduce a new visible charge-coupled device (CCD) camera-guided photoacoustic imaging (ViCPAI) system that integrates an ultrasound (US) transducer and a data acquisition platform with a CCD camera for positioning. The CCD camera accurately positions the US probe at the measurement location. The programmable MATLAB-based platform has an intuitive user interface. In vitro carbon fiber and in vivo animal experiments were performed to investigate the precise positioning and imaging capabilities of the ViCPAI system. We demonstrated real-time capturing of bilateral cerebral hemodynamic changes during (1) forelimb electrical stimulation under normal conditions, (2) forelimb stimulation after right brain focal photothrombotic ischemia (PTI) stroke, and (3) progression of KCl-induced cortical spreading depression (CSD). The ViCPAI system accurately located target areas and achieved reproducible positioning, which is crucial in animal and clinical experiments. In animal experiments, the ViCPAI system was used to investigate bilateral cerebral cortex responses to left forelimb electrical stimulation before and after stroke, showing that the CBV and SO2 in the right primary somatosensory cortex of the forelimb (S1FL) region were significantly changed by left forelimb electrical stimulation before stroke. No CBV or SO2 changes were observed in the bilateral cortex in the S1FL area in response to left forelimb electrical stimulation after stroke. While monitoring CSD progression, the ViCPAI system accurately locates the S1FL area and returns to the same position after the probe moves, demonstrating reproducible positioning and reducing positioning errors. The ViCPAI system utilizes the real-time precise positioning capability of CCD cameras to overcome various challenges in preclinical and clinical studies. Full article
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14 pages, 7887 KiB  
Article
Motion Compensation for 3D Multispectral Handheld Photoacoustic Imaging
by Chiho Yoon, Changyeop Lee, Keecheol Shin and Chulhong Kim
Biosensors 2022, 12(12), 1092; https://doi.org/10.3390/bios12121092 - 29 Nov 2022
Cited by 3 | Viewed by 1568
Abstract
Three-dimensional (3D) handheld photoacoustic (PA) and ultrasound (US) imaging performed using mechanical scanning are more useful than conventional 2D PA/US imaging for obtaining local volumetric information and reducing operator dependence. In particular, 3D multispectral PA imaging can capture vital functional information, such as [...] Read more.
Three-dimensional (3D) handheld photoacoustic (PA) and ultrasound (US) imaging performed using mechanical scanning are more useful than conventional 2D PA/US imaging for obtaining local volumetric information and reducing operator dependence. In particular, 3D multispectral PA imaging can capture vital functional information, such as hemoglobin concentrations and hemoglobin oxygen saturation (sO2), of epidermal, hemorrhagic, ischemic, and cancerous diseases. However, the accuracy of PA morphology and physiological parameters is hampered by motion artifacts during image acquisition. The aim of this paper is to apply appropriate correction to remove the effect of such motion artifacts. We propose a new motion compensation method that corrects PA images in both axial and lateral directions based on structural US information. 3D PA/US imaging experiments are performed on a tissue-mimicking phantom and a human wrist to verify the effects of the proposed motion compensation mechanism and the consequent spectral unmixing results. The structural motions and sO2 values are confirmed to be successfully corrected by comparing the motion-compensated images with the original images. The proposed method is expected to be useful in various clinical PA imaging applications (e.g., breast cancer, thyroid cancer, and carotid artery disease) that are susceptible to motion contamination during multispectral PA image analysis. Full article
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12 pages, 1325 KiB  
Article
Development of Stereo NIR-II Fluorescence Imaging System for 3D Tumor Vasculature in Small Animals
by Shih-Po Su, Syue-Liang Lin, Yang-Hsiang Chan, Yi-Jang Lee, Yun-Chen Lee, Pin-Xuan Zeng, Yi-Xuan Li, Muh-Hwa Yang and Huihua Kenny Chiang
Biosensors 2022, 12(2), 85; https://doi.org/10.3390/bios12020085 - 30 Jan 2022
Cited by 3 | Viewed by 3638
Abstract
Near-infrared-II (NIR-II, 1000–1700 nm) fluorescence imaging boasts high spatial resolution and deep tissue penetration due to low light scattering, reduced photon absorption, and low tissue autofluorescence. NIR-II biological imaging is applied mainly in the noninvasive visualization of blood vessels and tumors in deep [...] Read more.
Near-infrared-II (NIR-II, 1000–1700 nm) fluorescence imaging boasts high spatial resolution and deep tissue penetration due to low light scattering, reduced photon absorption, and low tissue autofluorescence. NIR-II biological imaging is applied mainly in the noninvasive visualization of blood vessels and tumors in deep tissue. In the study, a stereo NIR-II fluorescence imaging system was developed for acquiring three-dimension (3D) images on tumor vasculature in real-time, on top of the development of fluorescent semiconducting polymer dots (IR-TPE Pdots) with ultra-bright NIR-II fluorescence (1000–1400 nm) and high stability to perform long-term fluorescence imaging. The NIR-II imaging system only consists of one InGaAs camera and a moving stage to simulate left-eye view and right-eye view for the construction of 3D in-depth blood vessel images. The system was validated with blood vessel phantom of tumor-bearing mice and was applied successfully in obtaining 3D blood vessel images with 0.6 mm- and 5 mm-depth resolution and 0.15 mm spatial resolution. The NIR-II stereo vision provides precise 3D information on the tumor microenvironment and blood vessel path. Full article
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18 pages, 1920 KiB  
Article
Quantification Analysis of Sleep Based on Smartwatch Sensors for Parkinson’s Disease
by Yi-Feng Ko, Pei-Hsin Kuo, Ching-Fu Wang, Yu-Jen Chen, Pei-Chi Chuang, Shih-Zhang Li, Bo-Wei Chen, Fu-Chi Yang, Yu-Chun Lo, Yi Yang, Shuan-Chu Vina Ro, Fu-Shan Jaw, Sheng-Huang Lin and You-Yin Chen
Biosensors 2022, 12(2), 74; https://doi.org/10.3390/bios12020074 - 27 Jan 2022
Cited by 14 | Viewed by 5155
Abstract
Rapid eye movement (REM) sleep behavior disorder (RBD) is associated with Parkinson’s disease (PD). In this study, a smartwatch-based sensor is utilized as a convenient tool to detect the abnormal RBD phenomenon in PD patients. Instead, a questionnaire with sleep quality assessment and [...] Read more.
Rapid eye movement (REM) sleep behavior disorder (RBD) is associated with Parkinson’s disease (PD). In this study, a smartwatch-based sensor is utilized as a convenient tool to detect the abnormal RBD phenomenon in PD patients. Instead, a questionnaire with sleep quality assessment and sleep physiological indices, such as sleep stage, activity level, and heart rate, were measured in the smartwatch sensors. Therefore, this device can record comprehensive sleep physiological data, offering several advantages such as ubiquity, long-term monitoring, and wearable convenience. In addition, it can provide the clinical doctor with sufficient information on the patient’s sleeping patterns with individualized treatment. In this study, a three-stage sleep staging method (i.e., comprising sleep/awake detection, sleep-stage detection, and REM-stage detection) based on an accelerometer and heart-rate data is implemented using machine learning (ML) techniques. The ML-based algorithms used here for sleep/awake detection, sleep-stage detection, and REM-stage detection were a Cole–Kripke algorithm, a stepwise clustering algorithm, and a k-means clustering algorithm with predefined criteria, respectively. The sleep staging method was validated in a clinical trial. The results showed a statistically significant difference in the percentage of abnormal REM between the control group (1.6 ± 1.3; n = 18) and the PD group (3.8 ± 5.0; n = 20) (p = 0.04). The percentage of deep sleep stage in our results presented a significant difference between the control group (38.1 ± 24.3; n = 18) and PD group (22.0 ± 15.0, n = 20) (p = 0.011) as well. Further, our results suggested that the smartwatch-based sensor was able to detect the difference of an abnormal REM percentage in the control group (1.6 ± 1.3; n = 18), PD patient with clonazepam (2.0 ± 1.7; n = 10), and without clonazepam (5.7 ± 7.1; n = 10) (p = 0.007). Our results confirmed the effectiveness of our sensor in investigating the sleep stage in PD patients. The sensor also successfully determined the effect of clonazepam on reducing abnormal REM in PD patients. In conclusion, our smartwatch sensor is a convenient and effective tool for sleep quantification analysis in PD patients. Full article
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25 pages, 55289 KiB  
Article
Objective Numerical Evaluation of Diffuse, Optically Reconstructed Images Using Structural Similarity Index
by Vicky Mudeng, Minseok Kim and Se-woon Choe
Biosensors 2021, 11(12), 504; https://doi.org/10.3390/bios11120504 - 08 Dec 2021
Cited by 1 | Viewed by 2440
Abstract
Diffuse optical tomography is emerging as a non-invasive optical modality used to evaluate tissue information by obtaining the optical properties’ distribution. Two procedures are performed to produce reconstructed absorption and reduced scattering images, which provide structural information that can be used to locate [...] Read more.
Diffuse optical tomography is emerging as a non-invasive optical modality used to evaluate tissue information by obtaining the optical properties’ distribution. Two procedures are performed to produce reconstructed absorption and reduced scattering images, which provide structural information that can be used to locate inclusions within tissues with the assistance of a known light intensity around the boundary. These methods are referred to as a forward problem and an inverse solution. Once the reconstructed image is obtained, a subjective measurement is used as the conventional way to assess the image. Hence, in this study, we developed an algorithm designed to numerically assess reconstructed images to identify inclusions using the structural similarity (SSIM) index. We compared four SSIM algorithms with 168 simulated reconstructed images involving the same inclusion position with different contrast ratios and inclusion sizes. A multiscale, improved SSIM containing a sharpness parameter (MS-ISSIM-S) was proposed to represent the potential evaluation compared with the human visible perception. The results indicated that the proposed MS-ISSIM-S is suitable for human visual perception by demonstrating a reduction of similarity score related to various contrasts with a similar size of inclusion; thus, this metric is promising for the objective numerical assessment of diffuse, optically reconstructed images. Full article
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15 pages, 5248 KiB  
Article
Assessment of Brain Functional Activity Using a Miniaturized Head-Mounted Scanning Photoacoustic Imaging System in Awake and Freely Moving Rats
by Yuhling Wang, Tsung-Sheng Chu, Yan-Ren Lin, Chia-Hui Tsao, Chia-Hua Tsai, Tzong-Rong Ger, Li-Tzong Chen, Wun-Shaing Wayne Chang and Lun-De Liao
Biosensors 2021, 11(11), 429; https://doi.org/10.3390/bios11110429 - 30 Oct 2021
Cited by 4 | Viewed by 2386
Abstract
Understanding the relationship between brain function and natural behavior remains a significant challenge in neuroscience because there are very few convincing imaging/recording tools available for the evaluation of awake and freely moving animals. Here, we employed a miniaturized head-mounted scanning photoacoustic imaging (hmPAI) [...] Read more.
Understanding the relationship between brain function and natural behavior remains a significant challenge in neuroscience because there are very few convincing imaging/recording tools available for the evaluation of awake and freely moving animals. Here, we employed a miniaturized head-mounted scanning photoacoustic imaging (hmPAI) system to image real-time cortical dynamics. A compact photoacoustic (PA) probe based on four in-house optical fiber pads and a single custom-made 48-MHz focused ultrasound transducer was designed to enable focused dark-field PA imaging, and miniature linear motors were included to enable two-dimensional (2D) scanning. The total dimensions and weight of the proposed hmPAI system are only approximately 50 × 64 × 48 mm and 58.7 g (excluding cables). Our ex vivo phantom experimental tests revealed that a spatial resolution of approximately 0.225 mm could be achieved at a depth of 9 mm. Our in vivo results further revealed that the diameters of cortical vessels draining into the superior sagittal sinus (SSS) could be clearly imaged and continuously observed in both anesthetized rats and awake, freely moving rats. Statistical analysis showed that the full width at half maximum (FWHM) of the PA A-line signals (relative to the blood vessel diameter) was significantly increased in the selected SSS-drained cortical vessels of awake rats (0.58 ± 0.17 mm) compared with those of anesthetized rats (0.31 ± 0.09 mm) (p < 0.01, paired t-test). In addition, the number of pixels in PA B-scan images (relative to the cerebral blood volume (CBV)) was also significantly increased in the selected SSS-drained blood vessels of awake rats (107.66 ± 23.02 pixels) compared with those of anesthetized rats (81.99 ± 21.52 pixels) (p < 0.01, paired t-test). This outcome may result from a more active brain in awake rats than in anesthetized rats, which caused cerebral blood vessels to transport more blood to meet the increased nutrient demand of the tissue, resulting in an obvious increase in blood vessel volume. This hmPAI system was further validated for utility in the brains of awake and freely moving rats, showing that their natural behavior was unimpaired during vascular imaging, thereby providing novel opportunities for studies of behavior, cognition, and preclinical models of brain diseases. Full article
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17 pages, 40084 KiB  
Article
An Adjustable Dark-Field Acoustic-Resolution Photoacoustic Imaging System with Fiber Bundle-Based Illumination
by Yuhling Wang, De-Fu Jhang, Tsung-Sheng Chu, Chia-Hui Tsao, Chia-Hua Tsai, Chiung-Cheng Chuang, Tzong-Rong Ger, Li-Tzong Chen, Wun-Shaing Wayne Chang and Lun-De Liao
Biosensors 2021, 11(8), 262; https://doi.org/10.3390/bios11080262 - 03 Aug 2021
Cited by 4 | Viewed by 2559
Abstract
Photoacoustic (PA) imaging has become one of the major imaging methods because of its ability to record structural information and its high spatial resolution in biological tissues. Current commercialized PA imaging instruments are limited to varying degrees by their bulky size (i.e., the [...] Read more.
Photoacoustic (PA) imaging has become one of the major imaging methods because of its ability to record structural information and its high spatial resolution in biological tissues. Current commercialized PA imaging instruments are limited to varying degrees by their bulky size (i.e., the laser or scanning stage) or their use of complex optical components for light delivery. Here, we present a robust acoustic-resolution PA imaging system that consists of four adjustable optical fibers placed 90° apart around a 50 MHz high-frequency ultrasound (US) transducer. In the compact design concept of the PA probe, the relative illumination parameters (i.e., angles and fiber size) can be adjusted to fit different imaging applications in a single setting. Moreover, this design concept involves a user interface built in MATLAB. We first assessed the performance of our imaging system using in vitro phantom experiments. We further demonstrated the in vivo performance of the developed system in imaging (1) rat ear vasculature, (2) real-time cortical hemodynamic changes in the superior sagittal sinus (SSS) during left-forepaw electrical stimulation, and (3) real-time cerebral indocyanine green (ICG) dynamics in rats. Collectively, this alignment-free design concept of a compact PA probe without bulky optical lens systems is intended to satisfy the diverse needs in preclinical PA imaging studies. Full article
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14 pages, 2831 KiB  
Article
Measurement of Low Concentration of Micro-Plastics by Detection of Bioaffinity-Induced Particle Retention Using Surface Plasmon Resonance Biosensors
by Chen-Ji Huang, Gudivada Vijaya Narasimha, Yu-Cheng Chen, Jen-Kun Chen and Guo-Chung Dong
Biosensors 2021, 11(7), 219; https://doi.org/10.3390/bios11070219 - 03 Jul 2021
Cited by 9 | Viewed by 5337
Abstract
The issue of micro-plastics is becoming more and more important due to their ubiquity and the harm they cause to the human body. Therefore, evaluating the biological–physical interaction of micro-plastics with health cells has become the focus of many research efforts. This study [...] Read more.
The issue of micro-plastics is becoming more and more important due to their ubiquity and the harm they cause to the human body. Therefore, evaluating the biological–physical interaction of micro-plastics with health cells has become the focus of many research efforts. This study focuses on the movement mode and low concentration detection development for micro-plastics in surface plasmon resonance (SPR). Firstly, 20-micrometer micro-plastics were prepared by grinding and filtering, and the movement mode was explored; then, the characteristics were investigated by SPR. Chromatographic analysis showed that the surface charge of micro-plastics dominated the elution time, and estrogen receptors (ERs) played a supporting role. A difference of micro-plastics in SPR sensorgram was observed, inferring the micro-plastics’ movement in rolling mode on the ERs. Characteristics analysis indicated that the low particle number of micro-plastics on SPR showed a linear relationship with the response unit (RU). When ERs were immobilized on the biosensor, the force of the binding of micro-plastics to ERs under an ultra-low background was equivalent to the dissociation rate constant shown as follows: PS (0.05 nM) > PVC (0.09 nM) > PE (0.14 nM). The ELISA-like magnetic beads experiment verified the specificity between ERs and micro-plastics. Therefore, by using the SPR technique, a biological-derived over-occupation of PS was found via higher binding force with ERs and longer retention time. In the future, there will be considerable potential for micro-plastics issues, such as identification in natural samples, biomarking, real-time detection in specific environments/regions and human health subject. Full article
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Review

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20 pages, 4217 KiB  
Review
Assessment of Nanoparticle-Mediated Tumor Oxygen Modulation by Photoacoustic Imaging
by Maharajan Sivasubramanian and Leu-Wei Lo
Biosensors 2022, 12(5), 336; https://doi.org/10.3390/bios12050336 - 13 May 2022
Cited by 7 | Viewed by 2821
Abstract
Photoacoustic imaging (PAI) is an invaluable tool in biomedical imaging, as it provides anatomical and functional information in real time. Its ability to image at clinically relevant depths with high spatial resolution using endogenous tissues as contrast agents constitutes its major advantage. One [...] Read more.
Photoacoustic imaging (PAI) is an invaluable tool in biomedical imaging, as it provides anatomical and functional information in real time. Its ability to image at clinically relevant depths with high spatial resolution using endogenous tissues as contrast agents constitutes its major advantage. One of the most important applications of PAI is to quantify tissue oxygen saturation by measuring the differential absorption characteristics of oxy and deoxy Hb. Consequently, PAI can be utilized to monitor tumor-related hypoxia, which is a crucial factor in tumor microenvironments that has a strong influence on tumor invasiveness. Reactive oxygen species (ROS)-based therapies, such as photodynamic therapy, radiotherapy, and sonodynamic therapy, are oxygen-consuming, and tumor hypoxia is detrimental to their efficacy. Therefore, a persistent demand exists for agents that can supply oxygen to tumors for better ROS-based therapeutic outcomes. Among the various strategies, NP-mediated supplemental tumor oxygenation is especially encouraging due to its physio-chemical, tumor targeting, and theranostic properties. Here, we focus on NP-based tumor oxygenation, which includes NP as oxygen carriers and oxygen-generating strategies to alleviate hypoxia monitored by PAI. The information obtained from quantitative tumor oxygenation by PAI not only supports optimal therapeutic design but also serves as a highly effective tool to predict therapeutic outcomes. Full article
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18 pages, 15648 KiB  
Review
Double-Clad Fiber-Based Multifunctional Biosensors and Multimodal Bioimaging Systems: Technology and Applications
by Kathy Beaudette, Jiawen Li, Joseph Lamarre, Lucas Majeau and Caroline Boudoux
Biosensors 2022, 12(2), 90; https://doi.org/10.3390/bios12020090 - 01 Feb 2022
Cited by 4 | Viewed by 2726
Abstract
Optical fibers have been used to probe various tissue properties such as temperature, pH, absorption, and scattering. Combining different sensing and imaging modalities within a single fiber allows for increased sensitivity without compromising the compactness of an optical fiber probe. A double-clad fiber [...] Read more.
Optical fibers have been used to probe various tissue properties such as temperature, pH, absorption, and scattering. Combining different sensing and imaging modalities within a single fiber allows for increased sensitivity without compromising the compactness of an optical fiber probe. A double-clad fiber (DCF) can sustain concurrent propagation modes (single-mode, through its core, and multimode, through an inner cladding), making DCFs ideally suited for multimodal approaches. This study provides a technological review of how DCFs are used to combine multiple sensing functionalities and imaging modalities. Specifically, we discuss the working principles of DCF-based sensors and relevant instrumentation as well as fiber probe designs and functionalization schemes. Secondly, we review different applications using a DCF-based probe to perform multifunctional sensing and multimodal bioimaging. Full article
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25 pages, 5674 KiB  
Review
Traditional Microscopic Techniques Employed in Dental Adhesion Research—Applications and Protocols of Specimen Preparation
by Agnieszka Nawrocka, Ireneusz Piwonski, Salvatore Sauro, Annalisa Porcelli, Louis Hardan and Monika Lukomska-Szymanska
Biosensors 2021, 11(11), 408; https://doi.org/10.3390/bios11110408 - 21 Oct 2021
Cited by 8 | Viewed by 3148
Abstract
Microscopy is a traditional method to perform ex vivo/in vitro dental research. Contemporary microscopic techniques offer the opportunity to observe dental tissues and materials up to nanoscale level. The aim of this paper was to perform a literature review on four microscopic methods, [...] Read more.
Microscopy is a traditional method to perform ex vivo/in vitro dental research. Contemporary microscopic techniques offer the opportunity to observe dental tissues and materials up to nanoscale level. The aim of this paper was to perform a literature review on four microscopic methods, which are widely employed in dental studies concerning the evaluation of resin-dental adhesive interfaces—confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and atomic force microscopy (AFM). The literature search was performed using digital databases: PubMed, Web of Science and Scopus. On the basis of key words relevant to the topic and established eligibility criteria, finally 84 papers were included in the review. Presented microscopic techniques differ in their principle of operation and require specific protocols for specimen preparation. With regard to adhesion studies, microscopy assists in the description of several elements involved in adhesive bonding, as well as in the assessment of the condition of enamel surface and the most appropriate etching procedures. There are several factors determining the quality of the interaction between the substrates which could be recognized and a potential for further implementation of microscopic techniques in dental research could be recognized, especially when these techniques are used simultaneously or combined with spectroscopic methods. Through such microscopy techniques it is possible to provide clinically relevant conclusions and recommendations, which can be easily introduced for enamel-safe bonding and bonding protocols, as well as optimal pretreatments in dentine preparation. Full article
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