Biosensors

13 pages, 2462 KiB

Open AccessArticle

Folic Acid-Modified Fluorescent-Magnetic Nanoparticles for Efficient Isolation and Identification of Circulating Tumor Cells in Ovarian Cancer

by Yue Pan, Zhili Wang, Jialing Ma, Tongping Zhou, Zeen Wu, Pi Ding, Na Sun, Lifen Liu, Renjun Pei and Weipei Zhu

Biosensors 2022, 12(3), 184; https://doi.org/10.3390/bios12030184 - 21 Mar 2022

Cited by 15 | Viewed by 4112

Abstract

Ovarian cancer (OC) is a lethal disease occurring in women worldwide. Due to the lack of obvious clinical symptoms and sensitivity biomarkers, OC patients are often diagnosed in advanced stages and suffer a poor prognosis. Circulating tumor cells (CTCs), released from tumor sites [...] Read more.

Ovarian cancer (OC) is a lethal disease occurring in women worldwide. Due to the lack of obvious clinical symptoms and sensitivity biomarkers, OC patients are often diagnosed in advanced stages and suffer a poor prognosis. Circulating tumor cells (CTCs), released from tumor sites into the peripheral blood, have been recognized as promising biomarkers in cancer prognosis, treatment monitoring, and metastasis diagnosis. However, the number of CTCs in peripheral blood is low, and it is a technical challenge to isolate, enrich, and identify CTCs from the blood samples of patients. This work develops a simple, effective, and inexpensive strategy to capture and identify CTCs from OC blood samples using the folic acid (FA) and antifouling-hydrogel-modified fluorescent-magnetic nanoparticles. The hydrogel showed a good antifouling property against peripheral blood mononuclear cells (PBMCs). The FA was coupled to the hydrogel surface as the targeting molecule for the CTC isolation, held a good capture efficiency for SK-OV-3 cells (95.58%), and successfully isolated 2–12 CTCs from 10 OC patients’ blood samples. The FA-modified fluorescent-magnetic nanoparticles were successfully used for the capture and direct identification of CTCs from the blood samples of OC patients. Full article

(This article belongs to the Special Issue Nanoprobes for Tumor Theranostics)

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22 pages, 9460 KiB

Open AccessReview

DNA-Based Biosensors for the Biochemical Analysis: A Review

by Yu Hua, Jiaming Ma, Dachao Li and Ridong Wang

Biosensors 2022, 12(3), 183; https://doi.org/10.3390/bios12030183 - 20 Mar 2022

Cited by 63 | Viewed by 12109

Abstract

In recent years, DNA-based biosensors have shown great potential as the candidate of the next generation biomedical detection device due to their robust chemical properties and customizable biosensing functions. Compared with the conventional biosensors, the DNA-based biosensors have advantages such as wider detection [...] Read more.

In recent years, DNA-based biosensors have shown great potential as the candidate of the next generation biomedical detection device due to their robust chemical properties and customizable biosensing functions. Compared with the conventional biosensors, the DNA-based biosensors have advantages such as wider detection targets, more durable lifetime, and lower production cost. Additionally, the ingenious DNA structures can control the signal conduction near the biosensor surface, which could significantly improve the performance of biosensors. In order to show a big picture of the DNA biosensor’s advantages, this article reviews the background knowledge and recent advances of DNA-based biosensors, including the functional DNA strands-based biosensors, DNA hybridization-based biosensors, and DNA templated biosensors. Then, the challenges and future directions of DNA-based biosensors are discussed and proposed. Full article

(This article belongs to the Section Biosensor and Bioelectronic Devices)

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12 pages, 1767 KiB

Open AccessArticle

High-Sensitive Detection and Quantitative Analysis of Thyroid-Stimulating Hormone Using Gold-Nanoshell-Based Lateral Flow Immunoassay Device

by Santosh Kumar Bikkarolla, Sara E. McNamee, Paul Vance and James McLaughlin

Biosensors 2022, 12(3), 182; https://doi.org/10.3390/bios12030182 - 19 Mar 2022

Cited by 14 | Viewed by 5497

Abstract

Au nanoparticles (AuNPs) have been used as signal reporters in colorimetric lateral flow immunoassays (LFAs) for decades. However, it remains a major challenge to significantly improve the detection sensitivity of traditional LFAs due to the low brightness of AuNPs. As an alternative approach, [...] Read more.

Au nanoparticles (AuNPs) have been used as signal reporters in colorimetric lateral flow immunoassays (LFAs) for decades. However, it remains a major challenge to significantly improve the detection sensitivity of traditional LFAs due to the low brightness of AuNPs. As an alternative approach, we overcome this problem by utilizing 150 nm gold nanoshells (AuNSs) that were engineered by coating low-density silica nanoparticles with a thin layer of gold. AuNSs are dark green, have 14 times larger surface area, and are approximately 35 times brighter compared to AuNPs. In this study, we used detection of thyroid-stimulating hormone (TSH) in a proof-of-concept assay. The limit of detection (LOD) with AuNS-based LFA was 0.16 µIU/mL, which is 26 times more sensitive than the conventional colorimetric LFA that utilizes AuNP as a label. The dynamic range of the calibration curve was 0.16–9.5 µIU/mL, making it possible to diagnose both hyperthyroidism (<0.5 µIU/mL) and hypothyroidism (>5 µIU/mL) using AuNS-based LFA. Thus, the developed device has a strong potential for early screening and diagnosis of diseases related to the thyroid hormone. Full article

(This article belongs to the Section Biosensor Materials)

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15 pages, 10736 KiB

Open AccessArticle

Microfluidic-Assisted Fabrication of Dual-Coated pH-Sensitive Mesoporous Silica Nanoparticles for Protein Delivery

by Berrin Küçüktürkmen, Wali Inam, Fadak Howaili, Mariam Gouda, Neeraj Prabhakar, Hongbo Zhang and Jessica M. Rosenholm

Biosensors 2022, 12(3), 181; https://doi.org/10.3390/bios12030181 - 18 Mar 2022

Cited by 15 | Viewed by 3883

Abstract

Microfluidics has become a popular method for constructing nanosystems in recent years, but it can also be used to coat other materials with polymeric layers. The polymeric coating may serve as a diffusion barrier against hydrophilic compounds, a responsive layer for controlled release, [...] Read more.

Microfluidics has become a popular method for constructing nanosystems in recent years, but it can also be used to coat other materials with polymeric layers. The polymeric coating may serve as a diffusion barrier against hydrophilic compounds, a responsive layer for controlled release, or a functional layer introduced to a nanocomposite for achieving the desired surface chemistry. In this study, mesoporous silica nanoparticles (MSNs) with enlarged pores were synthesized to achieve high protein loading combined with high protein retention within the MSN system with the aid of a microfluidic coating. Thus, MSNs were first coated with a cationic polyelectrolyte, poly (diallyldimethylammonium chloride) (PDDMA), and to potentially further control the protein release, a second coating of a pH-sensitive polymer (spermine-modified acetylated dextran, SpAcDEX) was deposited by a designed microfluidic device. The protective PDDMA layer was first formed under aqueous conditions, whereby the bioactivity of the protein could be maintained. The second coating polymer, SpAcDEX, was preferred to provide pH-sensitive protein release in the intracellular environment. The optimized formulation was effectively taken up by the cells along with the loaded protein cargo. This proof-of-concept study thus demonstrated that the use of microfluidic technologies for the design of protein delivery systems has great potential in terms of creating multicomponent systems and preserving protein stability. Full article

(This article belongs to the Section Biosensor and Bioelectronic Devices)

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17 pages, 10725 KiB

Open AccessReview

Recent Advances in Surface Plasmon Resonance Sensors for Sensitive Optical Detection of Pathogens

by Joon-Ha Park, Yeon-Woo Cho and Tae-Hyung Kim

Biosensors 2022, 12(3), 180; https://doi.org/10.3390/bios12030180 - 17 Mar 2022

Cited by 56 | Viewed by 6823

Abstract

The advancement of science and technology has led to the recent development of highly sensitive pathogen biosensing techniques. The effective treatment of pathogen infections requires sensing technologies to not only be sensitive but also render results in real-time. This review thus summarises the [...] Read more.

The advancement of science and technology has led to the recent development of highly sensitive pathogen biosensing techniques. The effective treatment of pathogen infections requires sensing technologies to not only be sensitive but also render results in real-time. This review thus summarises the recent advances in optical surface plasmon resonance (SPR) sensor technology, which possesses the aforementioned advantages. Specifically, this technology allows for the detection of specific pathogens by applying nano-sized materials. This review focuses on various nanomaterials that are used to ensure the performance and high selectivity of SPR sensors. This review will undoubtedly accelerate the development of optical biosensing technology, thus allowing for real-time diagnosis and the timely delivery of appropriate treatments as well as preventing the spread of highly contagious pathogens. Full article

(This article belongs to the Topic Advances in Optical Sensors)

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20 pages, 1561 KiB

Open AccessReview

Microfluidics-Based Biosensing Platforms: Emerging Frontiers in Point-of-Care Testing SARS-CoV-2 and Seroprevalence

by Elda A. Flores-Contreras, Reyna Berenice González-González, Iram P. Rodríguez-Sánchez, Juan F. Yee-de León, Hafiz M. N. Iqbal and Everardo González-González

Biosensors 2022, 12(3), 179; https://doi.org/10.3390/bios12030179 - 17 Mar 2022

Cited by 13 | Viewed by 4319

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the ongoing COVID-19 (coronavirus disease-2019) outbreak and has unprecedentedly impacted the public health and economic sector. The pandemic has forced researchers to focus on the accurate and early detection of SARS-CoV-2, developing novel diagnostic tests. [...] Read more.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the ongoing COVID-19 (coronavirus disease-2019) outbreak and has unprecedentedly impacted the public health and economic sector. The pandemic has forced researchers to focus on the accurate and early detection of SARS-CoV-2, developing novel diagnostic tests. Among these, microfluidic-based tests stand out for their multiple benefits, such as their portability, low cost, and minimal reagents used. This review discusses the different microfluidic platforms applied in detecting SARS-CoV-2 and seroprevalence, classified into three sections according to the molecules to be detected, i.e., (1) nucleic acid, (2) antigens, and (3) anti-SARS-CoV-2 antibodies. Moreover, commercially available alternatives based on microfluidic platforms are described. Timely and accurate results allow healthcare professionals to perform efficient treatments and make appropriate decisions for infection control; therefore, novel developments that integrate microfluidic technology may provide solutions in the form of massive diagnostics to control the spread of infectious diseases. Full article

(This article belongs to the Special Issue Fundamentals of SARS-CoV-2 Biosensors)

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17 pages, 1971 KiB

Open AccessArticle

Application of a Novel Biosensor for Salivary Conductivity in Detecting Chronic Kidney Disease

by Chen-Wei Lin, Yuan-Hsiung Tsai, Yen-Pei Lu, Jen-Tsung Yang, Mei-Yen Chen, Tung-Jung Huang, Rui-Cian Weng and Chun-Wu Tung

Biosensors 2022, 12(3), 178; https://doi.org/10.3390/bios12030178 - 17 Mar 2022

Cited by 6 | Viewed by 3640

Abstract

The prevalence of chronic kidney disease (CKD) is increasing, and it brings an enormous healthcare burden. The traditional measurement of kidney function needs invasive blood tests, which hinders the early detection and causes low awareness of CKD. We recently designed a device with [...] Read more.

The prevalence of chronic kidney disease (CKD) is increasing, and it brings an enormous healthcare burden. The traditional measurement of kidney function needs invasive blood tests, which hinders the early detection and causes low awareness of CKD. We recently designed a device with miniaturized coplanar biosensing probes for measuring salivary conductivity at an extremely low volume (50 μL). Our preliminary data discovered that the salivary conductivity was significantly higher in the CKD patients. This cross-sectional study aims to validate the relationship between salivary conductivity and kidney function, represented by the estimated glomerular filtration rate (eGFR). We enrolled 214 adult participants with a mean age of 63.96 ± 13.53 years, of whom 33.2% were male. The prevalence rate of CKD, defined as eGFR < 60 mL/min/1.73 m², is 11.2% in our study. By multivariate linear regression analyses, we found that salivary conductivity was positively related to age and fasting glucose but negatively associated with eGFR. We further divided subjects into low, medium, and high groups according to the tertials of salivary conductivity levels. There was a significant trend for an increment of CKD patients from low to high salivary conductivity groups (4.2% vs. 12.5% vs. 16.9%, p for trend: 0.016). The receiver operating characteristic (ROC) curves disclosed an excellent performance by using salivary conductivity combined with age, gender, and body weight to diagnose CKD (AUC equal to 0.8). The adjusted odds ratio of CKD is 2.66 (95% CI, 1.10–6.46) in subjects with high salivary conductivity levels. Overall, salivary conductivity can serve as a good surrogate marker of kidney function; this real-time, non-invasive, and easy-to-use portable biosensing device may be a reliable tool for screening CKD. Full article

(This article belongs to the Special Issue Non-invasive Medical Devices for Detection and Monitoring within Healthcare)

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15 pages, 31741 KiB

Open AccessEditor’s ChoicePerspective

Preparation and Applications of Electrospun Nanofibers for Wearable Biosensors

by Tengzhou Xu, Guojing Ji, Hui Li, Jiaduo Li, Zhou Chen, Desire Emefa Awuye and Jie Huang

Biosensors 2022, 12(3), 177; https://doi.org/10.3390/bios12030177 - 17 Mar 2022

Cited by 15 | Viewed by 4506

Abstract

The emergence of nanotechnology has provided many new ideas and innovations in the field of biosensors. Electrospun nanofibers have many excellent properties such as high specific surface area, high porosity, low cost, high efficiency, and they can be combined with a variety of [...] Read more.

The emergence of nanotechnology has provided many new ideas and innovations in the field of biosensors. Electrospun nanofibers have many excellent properties such as high specific surface area, high porosity, low cost, high efficiency, and they can be combined with a variety of sensors. These remarkable features have a wide range of applications in the field of sensors such as monitoring air pollutants, highly sensitive pressure sensors, and biosensors for monitoring the pulse of the body. This paper summarizes the working principle and influencing factors of electrospinning nanofibers, and illustrates their applications in wearable biosensors. Full article

(This article belongs to the Special Issue Lab on a Chip Technology for Pathogen Detection and Disease Diagnosis)

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14 pages, 3046 KiB

Open AccessArticle

Simultaneously Acquiring Optical and Acoustic Properties of Individual Microalgae Cells Suspended in Water

by Hongjian Wang, Ran Liao, Zhihang Xiong, Zhao Wang, Jiajin Li, Qian Zhou, Yi Tao and Hui Ma

Biosensors 2022, 12(3), 176; https://doi.org/10.3390/bios12030176 - 15 Mar 2022

Cited by 5 | Viewed by 2679

Abstract

Microalgae play a vital role in aquatic ecological research, but the fine classification of these tiny and various microalgae cells is still challenging for the community. In this paper, we propose a multimodality technique to simultaneously acquire the polarized light scattering, fluorescence and [...] Read more.

Microalgae play a vital role in aquatic ecological research, but the fine classification of these tiny and various microalgae cells is still challenging for the community. In this paper, we propose a multimodality technique to simultaneously acquire the polarized light scattering, fluorescence and laser-induced acoustic wave signals originated from individual microalgae cells in water. Experiments of different species of Spirulina and different states of Microcystis have been conducted to test our experiment setup, and the results demonstrate that this method can well discriminate microalgae cells with pigment or microstructural differences. Moreover, with these modalities, the consumption of absorbed energy is evaluated quantitively, and a possible way to assess photosynthesis on a single-cell level is presented. This work is expected to be a powerful technique to probe the biophysical states of microalgae in the aquatic ecosystem. Full article

(This article belongs to the Section Environmental Biosensors and Biosensing)

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17 pages, 2921 KiB

Open AccessArticle

Fluorescence Sensors Based on Hydroxycarbazole for the Determination of Neurodegeneration-Related Halide Anions

by Víctor González-Ruiz, Ángel Cores, M. Mar Caja, Vellaisamy Sridharan, Mercedes Villacampa, M. Antonia Martín, Ana I. Olives and J. Carlos Menéndez

Biosensors 2022, 12(3), 175; https://doi.org/10.3390/bios12030175 - 14 Mar 2022

Cited by 7 | Viewed by 3008

Abstract

The environmental presence of anions of natural origin or anthropogenic origin is gradually increasing. As a tool to tackle this problem, carbazole derivatives are an attractive gateway to the development of luminescent chemosensors. Considering the different mechanisms proposed for anion recognition, the fluorescence [...] Read more.

The environmental presence of anions of natural origin or anthropogenic origin is gradually increasing. As a tool to tackle this problem, carbazole derivatives are an attractive gateway to the development of luminescent chemosensors. Considering the different mechanisms proposed for anion recognition, the fluorescence properties and anion-binding response of several newly synthesised carbazole derivatives were studied. Potential anion sensors were designed so that they combined the native fluorescence of carbazole with the presence of hydrogen bonding donor groups in critical positions for anion recognition. These compounds were synthesised by a feasible and non-expensive procedure using palladium-promoted cyclodehydrogenation of suitable diarylamine under microwave irradiation. In comparison to the other carbazole derivatives studied, 1-hydroxycarbazole proved to be useful as a fluorescent sensor for anions, as it was able to sensitively recognise fluoride and chloride anions by establishing hydrogen bond interactions through the hydrogen atoms on the pyrrolic nitrogen and the hydroxy group. Solvent effects and excited-state proton transfer (ESPT) of the carbazole derivatives are described to discard the role of the anions as Brönsted bases on the observed fluorescence behaviour of the sensors. The anion–sensor interaction was confirmed by ¹H-NMR. Molecular modelling was employed to propose a mode of recognition of the sensor in terms of complex stability and interatomic distances. 1-hydroxycarbazole was employed for the quantitation of fluoride and chloride anions in commercially available medicinal spring water and mouthwash samples. Full article

(This article belongs to the Special Issue Biosensors in Food Analysis and Environmental Detection)

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11 pages, 20017 KiB

Open AccessArticle

Cu₂O-Based Electrochemical Biosensor for Non-Invasive and Portable Glucose Detection

by Fabiane Fantinelli Franco, Richard A. Hogg and Libu Manjakkal

Biosensors 2022, 12(3), 174; https://doi.org/10.3390/bios12030174 - 14 Mar 2022

Cited by 32 | Viewed by 5869

Abstract

Electrochemical voltammetric sensors are some of the most promising types of sensors for monitoring various physiological analytes due to their implementation as non-invasive and portable devices. Advantages in reduced analysis time, cost-effectiveness, selective sensing, and simple techniques with low-powered circuits distinguish voltammetric sensors [...] Read more.

Electrochemical voltammetric sensors are some of the most promising types of sensors for monitoring various physiological analytes due to their implementation as non-invasive and portable devices. Advantages in reduced analysis time, cost-effectiveness, selective sensing, and simple techniques with low-powered circuits distinguish voltammetric sensors from other methods. In this work, we developed a Cu₂O-based non-enzymatic portable glucose sensor on a graphene paste printed on cellulose cloth. The electron transfer of Cu₂O in a NaOH alkaline medium and sweat equivalent solution at very low potential (+0.35 V) enable its implementation as a low-powered portable glucose sensor. The redox mechanism of the electrodes with the analyte solution was confirmed through cyclic voltammetry, differential pulse voltammetry, and electrochemical impedance spectroscopy studies. The developed biocompatible, disposable, and reproducible sensors showed sensing performance in the range of 0.1 to 1 mM glucose, with a sensitivity of 1082.5 ± 4.7% µA mM⁻¹ cm⁻² on Cu₂O coated glassy carbon electrode and 182.9 ± 8.83% µA mM⁻¹ cm⁻² on Cu₂O coated graphene printed electrodes, making them a strong candidate for future portable, non-invasive glucose monitoring devices on biodegradable substrates. For portable applications we demonstrated the sensor on artificial sweat in 0.1 M NaOH solution, indicating the Cu₂O nanocluster is selective to glucose from 0.0 to +0.6 V even in the presence of common interference such as urea and NaCl. Full article

(This article belongs to the Special Issue Non-invasive Medical Devices for Detection and Monitoring within Healthcare)

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13 pages, 2359 KiB

Open AccessArticle

Applying Machine Learning with Localized Surface Plasmon Resonance Sensors to Detect SARS-CoV-2 Particles

by Jiawei Liang, Wei Zhang, Yu Qin, Ying Li, Gang Logan Liu and Wenjun Hu

Biosensors 2022, 12(3), 173; https://doi.org/10.3390/bios12030173 - 13 Mar 2022

Cited by 13 | Viewed by 4130

Abstract

The sudden outbreak of COVID-19 rapidly developed into a global pandemic, which caused tens of millions of infections and millions of deaths. Although SARS-CoV-2 is known to cause COVID-19, effective approaches to detect SARS-CoV-2 using a convenient, rapid, accurate, and low-cost method are [...] Read more.

The sudden outbreak of COVID-19 rapidly developed into a global pandemic, which caused tens of millions of infections and millions of deaths. Although SARS-CoV-2 is known to cause COVID-19, effective approaches to detect SARS-CoV-2 using a convenient, rapid, accurate, and low-cost method are lacking. To date, most of the diagnostic methods for patients with early infections are limited to the detection of viral nucleic acids via polymerase chain reaction (PCR), or antigens, using an enzyme-linked immunosorbent assay or a chemiluminescence immunoassay. This study developed a novel method that uses localized surface plasmon resonance (LSPR) sensors, optical imaging, and artificial intelligence methods to directly detect the SARS-CoV-2 virus particles without any sample preparation. The virus concentration can be qualitatively and quantitatively detected in the range of 125.28 to 10⁶ vp/mL through a few steps within 12 min with a limit of detection (LOD) of 100 vp/mL. The accuracy of the SARS-CoV-2 positive or negative assessment was found to be greater than 97%, and this was demonstrated by establishing a regression machine learning model for the virus concentration prediction (R² > 0.95). Full article

(This article belongs to the Topic AI-enabled Sensor-related Technologies for Physiological Monitoring Designed to Advance Emergency Medical Care)

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21 pages, 2442 KiB

Open AccessEditor’s ChoiceArticle

Towards a Point-of-Care (POC) Diagnostic Platform for the Multiplex Electrochemiluminescent (ECL) Sensing of Mild Traumatic Brain Injury (mTBI) Biomarkers

by Milica Jović, Denis Prim, Edis Saini and Marc Emil Pfeifer

Biosensors 2022, 12(3), 172; https://doi.org/10.3390/bios12030172 - 11 Mar 2022

Cited by 7 | Viewed by 5696

Abstract

Globally, 70 million people are annually affected by TBI. A significant proportion of all TBI cases are actually mild TBI (concussion, 70–85%), which is considerably more difficult to diagnose due to the absence of apparent symptoms. Current clinical practice of diagnosing mTBI largely [...] Read more.

Globally, 70 million people are annually affected by TBI. A significant proportion of all TBI cases are actually mild TBI (concussion, 70–85%), which is considerably more difficult to diagnose due to the absence of apparent symptoms. Current clinical practice of diagnosing mTBI largely resides on the patients’ history, clinical aspects, and CT and MRI neuroimaging observations. The latter methods are costly, time-consuming, and not amenable for decentralized or accident site measurements. As an alternative (and/or complementary), mTBI diagnostics can be performed by detection of mTBI biomarkers from patients’ blood. Herein, we proposed two strategies for the detection of three mTBI-relevant biomarkers (GFAP, h-FABP, and S100β), in standard solutions and in human serum samples by using an electrochemiluminescence (ECL) immunoassay on (i) a commercial ECL platform in 96-well plate format, and (ii) a “POC-friendly” platform with disposable screen-printed carbon electrodes (SPCE) and a portable ECL reader. We further demonstrated a proof-of-concept for integrating three individually developed mTBI assays (“singleplex”) into a three-plex (“multiplex”) assay on a single SPCE using a spatially resolved ECL approach. The presented methodology demonstrates feasibility and a first step towards the development of a rapid POC multiplex diagnostic system for the detection of a mTBI biomarker panel on a single SPCE. Full article

(This article belongs to the Section Biosensors and Healthcare)

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14 pages, 13451 KiB

Open AccessArticle

A Hybrid Spiral Microfluidic Platform Coupled with Surface Acoustic Waves for Circulating Tumor Cell Sorting and Separation: A Numerical Study

by Rana Altay, Murat Kaya Yapici and Ali Koşar

Biosensors 2022, 12(3), 171; https://doi.org/10.3390/bios12030171 - 11 Mar 2022

Cited by 19 | Viewed by 5254

Abstract

The separation of circulating tumor cells (CTCs) from blood samples is crucial for the early diagnosis of cancer. During recent years, hybrid microfluidics platforms, consisting of both passive and active components, have been an emerging means for the label-free enrichment of circulating tumor [...] Read more.

The separation of circulating tumor cells (CTCs) from blood samples is crucial for the early diagnosis of cancer. During recent years, hybrid microfluidics platforms, consisting of both passive and active components, have been an emerging means for the label-free enrichment of circulating tumor cells due to their advantages such as multi-target cell processing with high efficiency and high sensitivity. In this study, spiral microchannels with different dimensions were coupled with surface acoustic waves (SAWs). Numerical simulations were conducted at different Reynolds numbers to analyze the performance of hybrid devices in the sorting and separation of CTCs from red blood cells (RBCs) and white blood cells (WBCs). Overall, in the first stage, the two-loop spiral microchannel structure allowed for the utilization of inertial forces for passive separation. In the second stage, SAWs were introduced to the device. Thus, five nodal pressure lines corresponding to the lateral position of the five outlets were generated. According to their physical properties, the cells were trapped and lined up on the corresponding nodal lines. The results showed that three different cell types (CTCs, RBCs, and WBCs) were successfully focused and collected from the different outlets of the microchannels by implementing the proposed multi-stage hybrid system. Full article

(This article belongs to the Special Issue Microfluidics for Biomedical Applications)

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17 pages, 3065 KiB

Open AccessArticle

Reverse Electrochemical Sensing of FLT3-ITD Mutations in Acute Myeloid Leukemia Using Gold Sputtered ZnO-Nanorod Configured DNA Biosensors

by Ramesh Thevendran, Kai Loong Foo, Mohd Hazwan Hussin, Emmanuel Jairaj Moses, Marimuthu Citartan, Haarindraprasad Rajintra Prasad and Solayappan Maheswaran

Biosensors 2022, 12(3), 170; https://doi.org/10.3390/bios12030170 - 10 Mar 2022

Cited by 6 | Viewed by 3163

Abstract

Detection of genetic mutations leading to hematological malignancies is a key factor in the early diagnosis of acute myeloid leukemia (AML). FLT3-ITD mutations are an alarming gene defect found commonly in AML patients associated with high cases of leukemia and low survival rates. [...] Read more.

Detection of genetic mutations leading to hematological malignancies is a key factor in the early diagnosis of acute myeloid leukemia (AML). FLT3-ITD mutations are an alarming gene defect found commonly in AML patients associated with high cases of leukemia and low survival rates. Available diagnostic assessments for FLT3-ITD are incapable of combining cost-effective detection platforms with high analytical performances. To circumvent this, we developed an efficient DNA biosensor for the recognition of AML caused by FLT3-ITD mutation utilizing electrochemical impedance characterization. The system was designed by adhering gold-sputtered zinc oxide (ZnO) nanorods onto interdigitated electrode (IDE) sensor chips. The sensing surface was biointerfaced with capture probes designed to hybridize with unmutated FLT3 sequences instead of the mutated FLT3-ITD gene, establishing a reverse manner of target detection. The developed biosensor demonstrated specific detection of mutated FLT3 genes, with high levels of sensitivity in response to analyte concentrations as low as 1 nM. The sensor also exhibited a stable functional life span of more than five weeks with good reproducibility and high discriminatory properties against FLT3 gene targets. Hence, the developed sensor is a promising tool for rapid and low-cost diagnostic applications relevant to the clinical prognosis of AML stemming from FLT3-ITD mutations. Full article

(This article belongs to the Special Issue Advances of Electrochemical Biosensors for the Detection of Oncological Disease)

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14 pages, 4384 KiB

Open AccessArticle

Ultra-Sensitive, Rapid and On-Site Sensing Harmful Ingredients Used in Aquaculture with Magnetic Fluid SERS

by Meizhen Zhang, Jingru Liao, Xianming Kong, Qian Yu, Miao Zhang and Alan X. Wang

Biosensors 2022, 12(3), 169; https://doi.org/10.3390/bios12030169 - 9 Mar 2022

Cited by 8 | Viewed by 3264

Abstract

The integration of surface-enhanced Raman scattering (SERS) spectroscopy with magnetic fluid provides significant utility in point-of-care (POC) testing applications. Bifunctional magnetic–plasmonic composites have been widely employed as SERS substrates. In this study, a simple and cost-effective approach was developed to synthesize magnetic–plasmonic SERS [...] Read more.

The integration of surface-enhanced Raman scattering (SERS) spectroscopy with magnetic fluid provides significant utility in point-of-care (POC) testing applications. Bifunctional magnetic–plasmonic composites have been widely employed as SERS substrates. In this study, a simple and cost-effective approach was developed to synthesize magnetic–plasmonic SERS substrates by decorating silver nanoparticles onto magnetic Fe₃O₄ nanoparticles (AgMNPs), which function both as SERS-active substrates and magnetic fluid particles. The strong magnetic responsivity from AgMNPs can isolate, concentrate, and detect target analytes from the irregular surface of fish skin rapidly. We fabricate a microfluid chip with three sample reservoirs that confine AgMNPs into ever smaller volumes under an applied magnetic field, which enhances the SERS signal and improves the detection limit by two orders of magnitude. The magnetic fluid POC sensor successfully detected malachite green from fish with excellent selectivity and high sensitivity down to the picomolar level. This work achieves a label-free, non-destructive optical sensing approach with promising potential for the detection of various harmful ingredients in food or the environment. Full article

(This article belongs to the Special Issue High-Efficiency Surface-Enhanced Raman Scattering Biosensing)

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9 pages, 17092 KiB

Open AccessCommunication

A Wearable Breath Sensor Based on Fiber-Tip Microcantilever

by Cong Zhao, Dan Liu, Zhihao Cai, Bin Du, Mengqiang Zou, Shuo Tang, Bozhe Li, Cong Xiong, Peng Ji, Lichao Zhang, Yuan Gong, Gaixia Xu, Changrui Liao and Yiping Wang

Biosensors 2022, 12(3), 168; https://doi.org/10.3390/bios12030168 - 7 Mar 2022

Cited by 21 | Viewed by 4577

Abstract

Respiration rate is an essential vital sign that requires monitoring under various conditions, including in strong electromagnetic environments such as in magnetic resonance imaging systems. To provide an electromagnetically-immune breath-sensing system, we propose an all-fiber-optic wearable breath sensor based on a fiber-tip microcantilever. [...] Read more.

Respiration rate is an essential vital sign that requires monitoring under various conditions, including in strong electromagnetic environments such as in magnetic resonance imaging systems. To provide an electromagnetically-immune breath-sensing system, we propose an all-fiber-optic wearable breath sensor based on a fiber-tip microcantilever. The microcantilever was fabricated on a fiber-tip by two-photon polymerization microfabrication based on femtosecond laser, so that a micro Fabry–Pérot (FP) interferometer was formed between the microcantilever and the end-face of the fiber. The cavity length of the micro FP interferometer was reduced as a result of the bending of the microcantilever induced by breath airflow. The signal of breath rate was rebuilt by detecting power variations of the FP interferometer reflected light and applying dynamic thresholds. The breath sensor achieved a high sensitivity of 0.8 nm/(m/s) by detecting the reflection spectrum upon applied flow velocities from 0.53 to 5.31 m/s. This sensor was also shown to have excellent thermal stability as its cross-sensitivity of airflow with respect to the temperature response was only 0.095 (m/s)/°C. When mounted inside a wearable surgical mask, the sensor demonstrated the capability to detect various breath patterns, including normal, fast, random, and deep breaths. We anticipate the proposed wearable breath sensor could be a useful and reliable tool for respiration rate monitoring. Full article

(This article belongs to the Collection Wearable Biosensors for Healthcare Applications)

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22 pages, 3994 KiB

Open AccessArticle

Explainable Artificial Intelligence and Wearable Sensor-Based Gait Analysis to Identify Patients with Osteopenia and Sarcopenia in Daily Life

by Jeong-Kyun Kim, Myung-Nam Bae, Kangbok Lee, Jae-Chul Kim and Sang Gi Hong

Biosensors 2022, 12(3), 167; https://doi.org/10.3390/bios12030167 - 7 Mar 2022

Cited by 22 | Viewed by 5416

Abstract

Osteopenia and sarcopenia can cause various senile diseases and are key factors related to the quality of life in old age. There is need for portable tools and methods that can analyze osteopenia and sarcopenia risks during daily life, rather than requiring a [...] Read more.

Osteopenia and sarcopenia can cause various senile diseases and are key factors related to the quality of life in old age. There is need for portable tools and methods that can analyze osteopenia and sarcopenia risks during daily life, rather than requiring a specialized hospital setting. Gait is a suitable indicator of musculoskeletal diseases; therefore, we analyzed the gait signal obtained from an inertial-sensor-based wearable gait device as a tool to manage bone loss and muscle loss in daily life. To analyze the inertial-sensor-based gait, the inertial signal was classified into seven gait phases, and descriptive statistical parameters were obtained for each gait phase. Subsequently, explainable artificial intelligence was utilized to analyze the contribution and importance of descriptive statistical parameters on osteopenia and sarcopenia. It was found that XGBoost yielded a high accuracy of 88.69% for osteopenia, whereas the random forest approach showed a high accuracy of 93.75% for sarcopenia. Transfer learning with a ResNet backbone exhibited appropriate performance but showed lower accuracy than the descriptive statistical parameter-based identification result. The proposed gait analysis method confirmed high classification accuracy and the statistical significance of gait factors that can be used for osteopenia and sarcopenia management. Full article

(This article belongs to the Special Issue Intelligent Biosignal Processing in Wearable and Implantable Sensors)

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19 pages, 7348 KiB

Open AccessArticle

A Single Wavelength Mid-Infrared Photoacoustic Spectroscopy for Noninvasive Glucose Detection Using Machine Learning

by Abdulrahman Aloraynan, Shazzad Rassel, Chao Xu and Dayan Ban

Biosensors 2022, 12(3), 166; https://doi.org/10.3390/bios12030166 - 7 Mar 2022

Cited by 27 | Viewed by 5844

Abstract

According to the International Diabetes Federation, 530 million people worldwide have diabetes, with more than 6.7 million reported deaths in 2021. Monitoring blood glucose levels is essential for individuals with diabetes, and developing noninvasive monitors has been a long-standing aspiration in diabetes management. [...] Read more.

According to the International Diabetes Federation, 530 million people worldwide have diabetes, with more than 6.7 million reported deaths in 2021. Monitoring blood glucose levels is essential for individuals with diabetes, and developing noninvasive monitors has been a long-standing aspiration in diabetes management. The ideal method for monitoring diabetes is to obtain the glucose concentration level with a fast, accurate, and pain-free measurement that does not require blood drawing or a surgical operation. Multiple noninvasive glucose detection techniques have been developed, including bio-impedance spectroscopy, electromagnetic sensing, and metabolic heat conformation. Nevertheless, reliability and consistency challenges were reported for these methods due to ambient temperature and environmental condition sensitivity. Among all the noninvasive glucose detection techniques, optical spectroscopy has rapidly advanced. A photoacoustic system has been developed using a single wavelength quantum cascade laser, lasing at a glucose fingerprint of 1080 cm

^{- 1}

for noninvasive glucose monitoring. The system has been examined using artificial skin phantoms, covering the normal and hyperglycemia blood glucose ranges. The detection sensitivity of the system has been improved to

\pm 25

mg/dL using a single wavelength for the entire range of blood glucose. Machine learning has been employed to detect glucose levels using photoacoustic spectroscopy in skin samples. Ensemble machine learning models have been developed to measure glucose concentration using classification techniques. The model has achieved a 90.4% prediction accuracy with 100% of the predicted data located in zones A and B of Clarke’s error grid analysis. This finding fulfills the US Food and Drug Administration requirements for glucose monitors. Full article

(This article belongs to the Section Optical and Photonic Biosensors)

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27 pages, 9193 KiB

Open AccessReview

Recent Progress on Micro-Fabricated Alkali Metal Vapor Cells

by Xuelei Wang, Mao Ye, Fei Lu, Yunkai Mao, Hao Tian and Jianli Li

Biosensors 2022, 12(3), 165; https://doi.org/10.3390/bios12030165 - 6 Mar 2022

Cited by 11 | Viewed by 5646

Abstract

Alkali vapor cells are the core components of atomic sensing instruments such as atomic gyroscopes, atomic magnetometers, atomic clocks, etc. Emerging integrated atomic sensing devices require high-performance miniaturized alkali vapor cells, especially micro-fabricated vapor cells. In this review, bonding methods for vapor cells [...] Read more.

Alkali vapor cells are the core components of atomic sensing instruments such as atomic gyroscopes, atomic magnetometers, atomic clocks, etc. Emerging integrated atomic sensing devices require high-performance miniaturized alkali vapor cells, especially micro-fabricated vapor cells. In this review, bonding methods for vapor cells of this kind are summarized in detail, including anodic bonding, sacrificial micro-channel bonding, and metal thermocompression bonding. Compared with traditional through-lighting schemes, researchers have developed novel methods for micro-fabricated vapor cells under both single- and double-beam schemes. In addition, emerging packaging methods for alkali metals in micro-fabricated vapor cells can be categorized as physical or chemical approaches. Physical methods include liquid transfer and wax pack filling. Chemical methods include the reaction of barium azide with rubidium chloride, ultraviolet light decomposition (of rubidium azide), and the high-temperature electrolysis of rubidium-rich glass. Finally, the application trend of micro-fabricated alkali vapor cells in the field of micro-scale gyroscopes, micro-scale atomic clocks, and especially micro-scale biomagnetometers is reviewed. Currently, the sensing industry has become a major driving force for the miniaturization of atomic sensing devices, and in the near future, the micro-fabricated alkali vapor cell technology of atomic sensing devices may experience extensive developments. Full article

(This article belongs to the Special Issue Micro/Nano and Electromagnetic Sensors)

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11 pages, 4630 KiB

Open AccessArticle

Self-Powered Wearable Biosensor in a Baby Diaper for Monitoring Neonatal Jaundice through a Hydrovoltaic-Biosensing Coupling Effect of ZnO Nanoarray

by Zirui Ning, Zhihe Long, Guangyou Yang, Lili Xing and Xinyu Xue

Biosensors 2022, 12(3), 164; https://doi.org/10.3390/bios12030164 - 6 Mar 2022

Cited by 14 | Viewed by 6396

Abstract

Neonatal jaundice refers to the abnormality of bilirubin metabolism for newborns, and wearable transcutaneous bilirubin meters for real-time measuring the bilirubin concentration is an insistent demand for the babies’ parents and doctors. In this paper, a self-powered wearable biosensor in a baby diaper [...] Read more.

Neonatal jaundice refers to the abnormality of bilirubin metabolism for newborns, and wearable transcutaneous bilirubin meters for real-time measuring the bilirubin concentration is an insistent demand for the babies’ parents and doctors. In this paper, a self-powered wearable biosensor in a baby diaper for real-time monitoring neonatal jaundice has been realized by the hydrovoltaic-biosensing coupling effect of ZnO nanoarray. Without external power supply, the system can work independently, and the hydrovoltaic output can be treated as both the power source and biosensing signal. The working mechanism is that the hydrovoltaic output arises from the urine flowing on ZnO nanoarray and the enzymatic reaction on the surface can influence the output. The sensing information can be transmitted through a wireless transmitter, and thus the parents and doctors can treat the neonatal jaundice of babies in time. This work can potentially promote the development of next generation of biosensors and physiological monitoring system, and expand the scope of self-powered technique and smart healthcare area. Full article

(This article belongs to the Section Wearable Biosensors)

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20 pages, 37978 KiB

Open AccessArticle

Effect of Graphene vs. Reduced Graphene Oxide in Gold Nanoparticles for Optical Biosensors—A Comparative Study

by Ana P. G. Carvalho, Elisabete C. B. A. Alegria, Alessandro Fantoni, Ana M. Ferraria, Ana M. Botelho do Rego and Ana P. C. Ribeiro

Biosensors 2022, 12(3), 163; https://doi.org/10.3390/bios12030163 - 4 Mar 2022

Cited by 15 | Viewed by 4128

Abstract

Aiming to develop a nanoparticle-based optical biosensor using gold nanoparticles (AuNPs) synthesized using green methods and supported by carbon-based nanomaterials, we studied the role of carbon derivatives in promoting AuNPs localized surface plasmon resonance (LSPR), as well as their morphology, dispersion, and stability. [...] Read more.

Aiming to develop a nanoparticle-based optical biosensor using gold nanoparticles (AuNPs) synthesized using green methods and supported by carbon-based nanomaterials, we studied the role of carbon derivatives in promoting AuNPs localized surface plasmon resonance (LSPR), as well as their morphology, dispersion, and stability. Carbon derivatives are expected to work as immobilization platforms for AuNPs, improving their analytical performance. Gold nanoparticles (AuNPs) were prepared using an eco-friendly approach in a single step by reduction of HAuCl₄·3H₂O using phytochemicals (from tea) which act as both reducing and capping agents. UV–Vis spectroscopy, transmission electron microscopy (TEM), zeta potential (ζ-potential), and X-ray photoelectron spectroscopy (XPS) were used to characterize the AuNPs and nanocomposites. The addition of reduced graphene oxide (rGO) resulted in greater dispersion of AuNPs on the rGO surface compared with carbon-based nanomaterials used as a support. Differences in morphology due to the nature of the carbon support were observed and are discussed here. AuNPs/rGO seem to be the most promising candidates for the development of LSPR biosensors among the three composites we studied (AuNPs/G, AuNPs/GO, and AuNPs/rGO). Simulations based on the Mie scattering theory have been used to outline the effect of the phytochemicals on LSPR, showing that when the presence of the residuals is limited to the formation of a thin capping layer, the quality of the plasmonic resonance is not affected. A further discussion of the application framework is presented. Full article

(This article belongs to the Special Issue Surface Plasmon Resonance for Biosensing)

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12 pages, 53299 KiB

Open AccessArticle

Magnetic Immunosensor Coupled to Enzymatic Signal for Determination of Genomic DNA Methylation

by Yitao Liang, Bin Zhang, Zexin Xue, Xuesong Ye and Bo Liang

Biosensors 2022, 12(3), 162; https://doi.org/10.3390/bios12030162 - 4 Mar 2022

Cited by 5 | Viewed by 3172

Abstract

Aberrations of genomic DNA methylation have been confirmed to be involved in the evolution of human cancer and have thus gained the potential to be depicted as biomarkers for cancer diagnostics and prognostic predictions, which implicates an urgent need for detection of total [...] Read more.

Aberrations of genomic DNA methylation have been confirmed to be involved in the evolution of human cancer and have thus gained the potential to be depicted as biomarkers for cancer diagnostics and prognostic predictions, which implicates an urgent need for detection of total genomic DNA methylation. In this work, we suggested an assay for the quantification of global DNA methylation, utilizing methylation specific antibody (5mC) modified magnetic beads (MBs) for immunorecognition and affinity enrichment. Subsequently, the captured DNA on the surface of MBs interacted with the glucose oxidase-conjugated DNA antibody whose catalytic reaction product was engaged in electrochemical detection of the overall level of DNA methylation on a PB-doped screen-printed electrode. With 15 pg of input DNA, which, to our best knowledge, is the lowest required amount of DNA without sodium bisulfite treatment or amplification, this test strategy was able to perceive as low as 5% methylation level within 70 min including the preparation of anti-5mC-MBs. We believe this detection technique offers a promising option to detect global DNA methylation in both academic and clinical scenarios. Full article

(This article belongs to the Special Issue Electrical/Optical Biosensing and Regulating Technology)

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27 pages, 2406 KiB

Open AccessReview

Recent Progress of Fluorescence Sensors for Histamine in Foods

by Gan Wu, Xilin Dou, Dapeng Li, Shihan Xu, Jicheng Zhang, Zhaoyang Ding and Jing Xie

Biosensors 2022, 12(3), 161; https://doi.org/10.3390/bios12030161 - 4 Mar 2022

Cited by 29 | Viewed by 7613

Abstract

Biological amines are organic nitrogen compounds that can be produced by the decomposition of spoiled food. As an important biological amine, histamine has played an important role in food safety. Many methods have been used to detect histamine in foods. Compared with traditional [...] Read more.

Biological amines are organic nitrogen compounds that can be produced by the decomposition of spoiled food. As an important biological amine, histamine has played an important role in food safety. Many methods have been used to detect histamine in foods. Compared with traditional analysis methods, fluorescence sensors as an adaptable detection tool for histamine in foods have the advantages of low cost, convenience, less operation, high sensitivity, and good visibility. In terms of food safety, fluorescence sensors have shown great utilization potential. In this review, we will introduce the applications and development of fluorescence sensors in food safety based on various types of materials. The performance and effectiveness of the fluorescence sensors are discussed in detail regarding their structure, luminescence mechanism, and recognition mechanism. This review may contribute to the exploration of the application of fluorescence sensors in food-related work. Full article

(This article belongs to the Special Issue Biosensors in Food Analysis and Environmental Detection)

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15 pages, 1911 KiB

Open AccessArticle

A HepG2 Cell-Based Biosensor That Uses Stainless Steel Electrodes for Hepatotoxin Detection

by Martin Rozman, Zala Štukovnik, Ajda Sušnik, Amirhossein Pakseresht, Matej Hočevar, Damjana Drobne and Urban Bren

Biosensors 2022, 12(3), 160; https://doi.org/10.3390/bios12030160 - 4 Mar 2022

Cited by 7 | Viewed by 3666

Abstract

Humans are frequently exposed to environmental hepatotoxins, which can lead to liver failure. Biosensors may be the best candidate for the detection of hepatotoxins because of their high sensitivity and specificity, convenience, time-saving, low cost, and extremely low detection limit. To investigate suitability [...] Read more.

Humans are frequently exposed to environmental hepatotoxins, which can lead to liver failure. Biosensors may be the best candidate for the detection of hepatotoxins because of their high sensitivity and specificity, convenience, time-saving, low cost, and extremely low detection limit. To investigate suitability of HepG2 cells for biosensor use, different methods of adhesion on stainless steel surfaces were investigated, with three groups of experiments performed in vitro. Cytotoxicity assays, which include the resazurin assay, the neutral red assay (NR), and the Coomassie Brilliant Blue (CBB) assay, were used to determine the viability of HepG2 cells exposed to various concentrations of aflatoxin B1 (AFB1) and isoniazid (INH) in parallel. The viability of the HepG2 cells on the stainless steel surface was quantitatively and qualitatively examined with different microscopy techniques. A simple cell-based electrochemical biosensor was developed by evaluating the viability of the HepG2 cells on the stainless steel surface when exposed to various concentrations of AFB1 and INH by using electrochemical impedance spectroscopy (EIS). The results showed that HepG2 cells can adhere to the metal surface and could be used as part of the biosensor to determine simple hepatotoxic samples. Full article

(This article belongs to the Special Issue Cell Based Biosensors)

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20 pages, 5318 KiB

Open AccessArticle

Cuff-Less Blood Pressure Prediction from ECG and PPG Signals Using Fourier Transformation and Amplitude Randomization Preprocessing for Context Aggregation Network Training

by Treesukon Treebupachatsakul, Apivitch Boosamalee, Siratchakrit Shinnakerdchoke, Suejit Pechprasarn and Nuntachai Thongpance

Biosensors 2022, 12(3), 159; https://doi.org/10.3390/bios12030159 - 4 Mar 2022

Cited by 7 | Viewed by 5486

Abstract

This research proposes an algorithm to preprocess photoplethysmography (PPG) and electrocardiogram (ECG) signals and apply the processed signals to the context aggregation network-based deep learning to achieve higher accuracy of continuous systolic and diastolic blood pressure monitoring than other reported algorithms. The preprocessing [...] Read more.

This research proposes an algorithm to preprocess photoplethysmography (PPG) and electrocardiogram (ECG) signals and apply the processed signals to the context aggregation network-based deep learning to achieve higher accuracy of continuous systolic and diastolic blood pressure monitoring than other reported algorithms. The preprocessing method consists of the following steps: (1) acquiring the PPG and ECG signals for a two second window at a sampling rate of 125 Hz; (2) separating the signals into an array of 250 data points corresponding to a 2 s data window; (3) randomizing the amplitude of the PPG and ECG signals by multiplying the 2 s frames by a random amplitude constant to ensure that the neural network can only learn from the frequency information accommodating the signal fluctuation due to instrument attachment and installation; (4) Fourier transforming the windowed PPG and ECG signals obtaining both amplitude and phase data; (5) normalizing both the amplitude and the phase of PPG and ECG signals using z-score normalization; and (6) training the neural network using four input channels (the amplitude and the phase of PPG and the amplitude and the phase of ECG), and arterial blood pressure signal in time-domain as the label for supervised learning. As a result, the network can achieve a high continuous blood pressure monitoring accuracy, with the systolic blood pressure root mean square error of 7 mmHg and the diastolic root mean square error of 6 mmHg. These values are within the error range reported in the literature. Note that other methods rely only on mathematical models for the systolic and diastolic values, whereas the proposed method can predict the continuous signal without degrading the measurement performance and relying on a mathematical model. Full article

(This article belongs to the Special Issue Biophysical Sensors for Biomedical/Health Monitoring Applications)

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7 pages, 1793 KiB

Open AccessCommunication

Wafer-Scale LSPR Substrate: Oblique Deposition of Gold on a Patterned Sapphire Substrate

by Kihyeun Kim, Ki Joong Lee, Na Rae Jo, Eun-Jung Jo, Yong-Beom Shin and Min-Gon Kim

Biosensors 2022, 12(3), 158; https://doi.org/10.3390/bios12030158 - 3 Mar 2022

Cited by 6 | Viewed by 3043

Abstract

Label-free detection of biomolecules using localized surface plasmon resonance (LSPR) substrates is a highly attractive method for point-of-care (POC) testing. One of the remaining challenges to developing LSPR-based POC devices is to fabricate the LSPR substrates with large-scale, reproducible, and high-throughput. Herein, a [...] Read more.

Label-free detection of biomolecules using localized surface plasmon resonance (LSPR) substrates is a highly attractive method for point-of-care (POC) testing. One of the remaining challenges to developing LSPR-based POC devices is to fabricate the LSPR substrates with large-scale, reproducible, and high-throughput. Herein, a fabrication strategy for wafer-scale LSPR substrates is demonstrated using reproducible, high-throughput techniques, such as nanoimprint lithography, wet-etching, and thin film deposition. A transparent sapphire wafer, on which SiO₂-nanodot hard masks were formed via nanoimprint lithography, was anisotropically etched by a mixed solution of H₂SO₄ and H₃PO₄, resulting in a patterned sapphire substrate (PSS). An LSPR substrate was finally fabricated by oblique deposition of Au onto the PSS, which was then applied to label-free detection of the binding events of biomolecules. To the best of our knowledge, this paper is the first report on the application of the PSS used as an LSPR template by obliquely depositing a metal. Full article

(This article belongs to the Special Issue Plasmonic Sensors: A New Frontier in Nanotechnology)

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17 pages, 3687 KiB

Open AccessArticle

Portable FRET-Based Biosensor Device for On-Site Lead Detection

by Wei-Qun Lai, Yu-Fen Chang, Fang-Ning Chou and De-Ming Yang

Biosensors 2022, 12(3), 157; https://doi.org/10.3390/bios12030157 - 2 Mar 2022

Cited by 15 | Viewed by 4980

Abstract

Most methods for measuring environmental lead (Pb) content are time consuming, expensive, hazardous, and restricted to specific analytical systems. To provide a facile, safe tool to detect Pb, we created pMet-lead, a portable fluorescence resonance energy transfer (FRET)-based Pb-biosensor. The pMet-lead device comprises [...] Read more.

Most methods for measuring environmental lead (Pb) content are time consuming, expensive, hazardous, and restricted to specific analytical systems. To provide a facile, safe tool to detect Pb, we created pMet-lead, a portable fluorescence resonance energy transfer (FRET)-based Pb-biosensor. The pMet-lead device comprises a 3D-printed frame housing a 405-nm laser diode—an excitation source for fluorescence emission images (YFP and CFP)—accompanied by optical filters, a customized sample holder with a Met-lead 1.44 M1 (the most recent version)-embedded biochip, and an optical lens aligned for smartphone compatibility. Measuring the emission ratios (Y/C) of the FRET components enabled Pb detection with a dynamic range of nearly 2 (1.96), a pMet-lead/Pb dissociation constant (K_d) 45.62 nM, and a limit of detection 24 nM (0.474 μg/dL, 4.74 ppb). To mitigate earlier problems with a lack of selectivity for Pb vs. zinc, we preincubated samples with tricine, a low-affinity zinc chelator. We validated the pMet-lead measurements of the characterized laboratory samples and unknown samples from six regions in Taiwan by inductively coupled plasma mass spectrometry (ICP-MS). Notably, two unknown samples had Y/C ratios significantly higher than that of the control (3.48 ± 0.08 and 3.74 ± 0.12 vs. 2.79 ± 0.02), along with Pb concentrations (10.6 ppb and 15.24 ppb) above the WHO-permitted level of 10 ppb in tap water, while the remaining four unknowns showed no detectable Pb upon ICP-MS. These results demonstrate that pMet-lead provides a rapid, sensitive means for on-site Pb detection in water from the environment and in living/drinking supply systems to prevent potential Pb poisoning. Full article

(This article belongs to the Special Issue Sensors for Environmental Monitoring and Food Safety)

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19 pages, 2617 KiB

Open AccessReview

Droplet Manipulation under a Magnetic Field: A Review

by Gui-Ping Zhu, Qi-Yue Wang, Zhao-Kun Ma, Shi-Hua Wu and Yi-Pan Guo

Biosensors 2022, 12(3), 156; https://doi.org/10.3390/bios12030156 - 2 Mar 2022

Cited by 30 | Viewed by 6009

Abstract

The magnetic manipulation of droplets is one of the emerging magnetofluidic technologies that integrate multiple disciplines, such as electromagnetics, fluid mechanics and so on. The directly driven droplets are mainly composed of ferrofluid or liquid metal. This kind of magnetically induced droplet manipulation [...] Read more.

The magnetic manipulation of droplets is one of the emerging magnetofluidic technologies that integrate multiple disciplines, such as electromagnetics, fluid mechanics and so on. The directly driven droplets are mainly composed of ferrofluid or liquid metal. This kind of magnetically induced droplet manipulation provides a remote, wireless and programmable approach beneficial for research and engineering applications, such as drug synthesis, biochemistry, sample preparation in life sciences, biomedicine, tissue engineering, etc. Based on the significant growth in the study of magneto droplet handling achieved over the past decades, further and more profound explorations in this field gained impetus, raising concentrations on the construction of a comprehensive working mechanism and the commercialization of this technology. Current challenges faced are not limited to the design and fabrication of the magnetic field, the material, the acquisition of precise and stable droplet performance, other constraints in processing speed and so on. The rotational devices or systems could give rise to additional issues on bulky appearance, high cost, low reliability, etc. Various magnetically introduced droplet behaviors, such as deformation, displacement, rotation, levitation, splitting and fusion, are mainly introduced in this work, involving the basic theory, functions and working principles. Full article

(This article belongs to the Special Issue Microfluidics for Biomedical Applications)

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14 pages, 2374 KiB

Open AccessCommunication

Automatic and Accurate Sleep Stage Classification via a Convolutional Deep Neural Network and Nanomembrane Electrodes

by Kangkyu Kwon, Shinjae Kwon and Woon-Hong Yeo

Biosensors 2022, 12(3), 155; https://doi.org/10.3390/bios12030155 - 2 Mar 2022

Cited by 20 | Viewed by 3899

Abstract

Sleep stage classification is an essential process of diagnosing sleep disorders and related diseases. Automatic sleep stage classification using machine learning has been widely studied due to its higher efficiency compared with manual scoring. Typically, a few polysomnography data are selected as input [...] Read more.

Sleep stage classification is an essential process of diagnosing sleep disorders and related diseases. Automatic sleep stage classification using machine learning has been widely studied due to its higher efficiency compared with manual scoring. Typically, a few polysomnography data are selected as input signals, and human experts label the corresponding sleep stages manually. However, the manual process includes human error and inconsistency in the scoring and stage classification. Here, we present a convolutional neural network (CNN)-based classification method that offers highly accurate, automatic sleep stage detection, validated by a public dataset and new data measured by wearable nanomembrane dry electrodes. First, our study makes a training and validation model using a public dataset with two brain signal and two eye signal channels. Then, we validate this model with a new dataset measured by a set of nanomembrane electrodes. The result of the automatic sleep stage classification shows that our CNN model with multi-taper spectrogram pre-processing achieved 88.85% training accuracy on the validation dataset and 81.52% prediction accuracy on our laboratory dataset. These results validate the reliability of our classification method on the standard polysomnography dataset and the transferability of our CNN model for other datasets measured with the wearable electrodes. Full article

(This article belongs to the Special Issue Smart, Connected, and Portable Biosensors and Bioelectronics for Advancing Human Healthcare, Disease Diagnosis, and Therapeutics)

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