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Nano/Micro Technologies for Biosensors: A Themed Issue in Honor of...
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Nano/Micro Technologies for Biosensors: A Themed Issue in Honor of Prof. Dr. Chung-Chiun Liu

A special issue of Biosensors (ISSN 2079-6374). This special issue belongs to the section "Nano- and Micro-Technologies in Biosensors".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 19962

Special Issue Editor

Dr. Yuan Zhang

E-Mail Website
Guest Editor
Materials Genome Institute, Shanghai University, Shanghai 200444, China
Interests: functional nanomaterials; electrochemical biosensor; biomarker detection, cancer diagnosis

Special Issue Information

Dear Colleagues,

Significant changes in lifestyle and personalized healthcare are expected to raise the demand for low-cost point-of-care (POC) diagnostic devices. The use of affordable rapid diagnostic tests could greatly reduce the global diseases burden, especially in the chronic disease diagnosis as well as early cancer screening. The employment of advanced and unique nanostructured materials enables the sensitive and specific detection of molecular biomarkers and also offers benefits in the immobilization of bioreceptors. Microfabrication technology has been widely utilized to fabricate different transducers for the diagnosis and monitoring of diseases, including electrochemical, optical, piezoelectric, surface plasmon resonance, semiconductor, and so on. The combination of micro and nano technologies has promoted the development of many new signal transduction technologies and enables the possibility of timely, portable, sensitive, and accurate analysis. Such devices could also be used for simple and rapid in vivo operation such as biologically relevant measurements in living cells. The nano–micro integrated platforms have shown the potential to revolutionize the future of personal health management as well as disease diagnosis and prognosis.

As one of the pioneers in the field of electrochemical sensing and biosensing, Professor Chung-Chiun Liu has made outstanding contributions in biomedical sensors, micro-fabrication, and micro-machining techniques. This Special Issue will honor Professor Chung-Chiun Liu, who is a distinguished University Professor and Wallace R. Persons Professor of Sensor Technology and Control at Case Western Reserve University (CWRU).

Dr. Yuan Zhang
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biosensors is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • chronic disease diagnosis
  • cancer diagnostics
  • microsensor chips
  • nano-sensing technologies
  • biomarkers detection
  • point-of-care biosensors

Published Papers (9 papers)

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Research

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16 pages, 5757 KiB  
Article
Simultaneous and Sensitive Detection of Three Pesticides Using a Functional Poly(Sulfobetaine Methacrylate)-Coated Paper-Based Colorimetric Sensor
by Jingyang Zhu, Xinru Yin, Weiyi Zhang, Meilian Chen, Dongsheng Feng, Yong Zhao and Yongheng Zhu
Biosensors 2023, 13(3), 309; https://doi.org/10.3390/bios13030309 - 22 Feb 2023
Cited by 6 | Viewed by 1654
Abstract
Chlorpyrifos (CHL), profenofos (PRO) and cypermethrin (CYP) are widely used in combination to increase crop yields. However, these three pesticides can cause serious harm to human health and do not easily degrade. In this study, a novel visible paper sensor has been prepared [...] Read more.
Chlorpyrifos (CHL), profenofos (PRO) and cypermethrin (CYP) are widely used in combination to increase crop yields. However, these three pesticides can cause serious harm to human health and do not easily degrade. In this study, a novel visible paper sensor has been prepared successfully and different colorimetric reactions were utilized to detect the three pesticides simultaneously. The sensor was constructed by grafting a zwitterionic polymer onto a cellulose filter (CF) and placing it on a glass surface modified with PDMS. The branch shape was designed to form multiple detection areas, which were modified with specific pesticides and corresponding chromogenic reagents. The as-prepared colorimetric platform exhibited high sensitivity, a short detection time, a good linear response and a low detection limit (LOD) for the three pesticides (chlorpyrifos: y = 46.801 − 1.939x, R2 = 0.983, LOD = 0.235 mg/L; profenofos: y = 40.068 + 42.5x, R2 = 0.988, LOD = 4.891 mg/L; cypermethrin: y = 51.993 + 1.474x, R2 = 0.993, LOD = 4.053 mg/L). The comparison of the results obtained by the proposed paper sensor and those obtained by spectrophotometry further revealed the stability and reliability of the paper sensor. In particular, the color intensity of the interaction between the pesticides and coloring agents could be directly observed by the human eye. The consistency of the colorimetric/optical assay was proven in real target pesticide samples. Thus, this sensing strategy provides a portable, cost-effective, accurate and visualized paper platform, which could be suitable for application in the fruit and vegetable industry for monitoring CHL, PRO and CYP in parallel. Full article
(This article belongs to the Special Issue Nano/Micro Technologies for Biosensors: A Themed Issue in Honor of Prof. Dr. Chung-Chiun Liu)
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14 pages, 3323 KiB  
Article
A Novel Detachable, Reusable, and Versatile Acoustic Tweezer Manipulation Platform for Biochemical Analysis and Detection Systems
by Yukai Liu, Miaomiao Ji, Yichi Zhang, Xiaojun Qiao, Nanxin Yu, Chenxi Ding, Lingxiao Yang, Rui Feng, Xiujian Chou and Wenping Geng
Biosensors 2022, 12(12), 1179; https://doi.org/10.3390/bios12121179 - 18 Dec 2022
Cited by 1 | Viewed by 1666
Abstract
Multifunctional, integrated, and reusable operating platforms are highly sought after in biochemical analysis and detection systems. In this study, we demonstrated a novel detachable, reusable acoustic tweezer manipulation platform that is flexible and versatile. The free interchangeability of different detachable microchannel devices on [...] Read more.
Multifunctional, integrated, and reusable operating platforms are highly sought after in biochemical analysis and detection systems. In this study, we demonstrated a novel detachable, reusable acoustic tweezer manipulation platform that is flexible and versatile. The free interchangeability of different detachable microchannel devices on the acoustic tweezer platform was achieved by adding a waveguide layer (glass) and a coupling layer (polydimethylsiloxane (PDMS) polymer film). We designed and demonstrated the detachable multifunctional acoustic tweezer platform with three cell manipulation capabilities. In Demo I, the detachable acoustic tweezer platform is demonstrated to have the capability for parallel processing and enrichment of the sample. In Demo II, the detachable acoustic tweezer platform with capability for precise cell alignment is demonstrated. In Demo III, it was demonstrated that the detachable acoustic tweezer platform has the capability for the separation and purification of cells. Through experiments, our acoustic tweezer platform has good acoustic retention ability, reusability, and stability. More capabilities can be expanded in the future. It provides a simple, economical, and multifunctional reusable operating platform solution for biochemical analysis and detection systems. Full article
(This article belongs to the Special Issue Nano/Micro Technologies for Biosensors: A Themed Issue in Honor of Prof. Dr. Chung-Chiun Liu)
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10 pages, 2235 KiB  
Communication
Reporter Molecules Embedded Au@Ag Core-Shell Nanospheres as SERS Nanotags for Cardiac Troponin I Detection
by Ding Wang, Yiru Zhao, Shen Zhang, Liping Bao, Huijun Li, Jingcheng Xu, Bin He and Xumin Hou
Biosensors 2022, 12(12), 1108; https://doi.org/10.3390/bios12121108 - 01 Dec 2022
Cited by 5 | Viewed by 1619
Abstract
Rapid and accurate detection of acute myocardial infarction can improve patients’ chances of survival. Cardiac troponin I (cTn I) is an important diagnostic biomarker for acute myocardial infarction. However, current immunoassays are insufficient to accurately measure cTn I, as they have limited detection [...] Read more.
Rapid and accurate detection of acute myocardial infarction can improve patients’ chances of survival. Cardiac troponin I (cTn I) is an important diagnostic biomarker for acute myocardial infarction. However, current immunoassays are insufficient to accurately measure cTn I, as they have limited detection sensitivity and are time-consuming. Surface-enhanced Raman scattering (SERS) is a brilliant fingerprints diagnostic technique characterised by ultrasensitivity, fast response, and qualitative and quantitative analysis capabilities. In this study, reporter molecules (4-Mercaptobenzoic acid, 4-MBA) embedded Au@Ag core-shell nanospheres as SERS nanotags were prepared for the detection of cTn I. As the Raman reporters were embedded between the core and the shell, they could be protected from the external environment and nanoparticle aggregation. Excellent SERS performances were obtained due to the enhanced local electromagnetic field in the gap of core and shell metals. In a standard phosphate buffered saline (PBS) environment, the limit of detection for cTn I was 0.0086 ng mL−1 (8.6 ppt) with a good linear relationship. The excellent Raman detection performance was attributed to the localized surface plasmon resonance effect and strong electromagnetic field enhancement effect produced by the gap between the Au core and the Ag shell. The SERS nanotags we prepared were facile to synthesize, and the analysis procedure could be completed quickly (15 min), which made the detection of cTn I faster. Therefore, the proposed SERS nanotags have significant potential to be a faster and more accurate tool for acute myocardial infarction diagnostics. Full article
(This article belongs to the Special Issue Nano/Micro Technologies for Biosensors: A Themed Issue in Honor of Prof. Dr. Chung-Chiun Liu)
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10 pages, 3179 KiB  
Communication
Alkaline Phosphatase Electrochemical Micro-Sensor Based on 3D Graphene Networks for the Monitoring of Osteoblast Activity
by Ning Zhao, Jiaci Shi, Ming Li, Pengcheng Xu, Xuefeng Wang and Xinxin Li
Biosensors 2022, 12(6), 406; https://doi.org/10.3390/bios12060406 - 13 Jun 2022
Cited by 2 | Viewed by 2059
Abstract
Alkaline phosphatase (ALP) is a significant biomarker that indicates osteoblast activity and skeletal growth. Efficient ALP detection methods are essential in drug development and clinical diagnosis. In this work, we developed an in-situ synthesized three-dimensional graphene networks (3DGNs)-based electrochemical sensor to determine ALP [...] Read more.
Alkaline phosphatase (ALP) is a significant biomarker that indicates osteoblast activity and skeletal growth. Efficient ALP detection methods are essential in drug development and clinical diagnosis. In this work, we developed an in-situ synthesized three-dimensional graphene networks (3DGNs)-based electrochemical sensor to determine ALP activity. The sensor employs an ALP enzymatic conversion of non-electroactive substrate to electroactive product and presents the ALP activity as an electrochemical signal. With 3DGNs as the catalyst and signal amplifier, a sample consumption of 5 μL and an incubation time of 2 min are enough for the sensor to detect a wide ALP activity range from 10 to 10,000 U/L, with a limit of detection of 5.70 U/L. This facile fabricated sensor provides a quick response, cost-effective and non-destructive approach for monitoring living adherent osteoblast cell activity and holds promise for ALP quantification in other biological systems and clinical samples. Full article
(This article belongs to the Special Issue Nano/Micro Technologies for Biosensors: A Themed Issue in Honor of Prof. Dr. Chung-Chiun Liu)
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13 pages, 4054 KiB  
Article
Enhanced Detection in Droplet Microfluidics by Acoustic Vortex Modulation of Particle Rings and Particle Clusters via Asymmetric Propagation of Surface Acoustic Waves
by Yukai Liu, Miaomiao Ji, Nanxin Yu, Caiqin Zhao, Gang Xue, Wenxiao Fu, Xiaojun Qiao, Yichi Zhang, Xiujian Chou and Wenping Geng
Biosensors 2022, 12(6), 399; https://doi.org/10.3390/bios12060399 - 10 Jun 2022
Cited by 5 | Viewed by 2305
Abstract
As a basis for biometric and chemical analysis, issues of how to dilute or concentrate substances such as particles or cells to specific concentrations have long been of interest to researchers. In this study, travelling surface acoustic wave (TSAW)-based devices with three frequencies [...] Read more.
As a basis for biometric and chemical analysis, issues of how to dilute or concentrate substances such as particles or cells to specific concentrations have long been of interest to researchers. In this study, travelling surface acoustic wave (TSAW)-based devices with three frequencies (99.1, 48.8, 20.4 MHz) have been used to capture the suspended Polystyrene (PS) microspheres of various sizes (5, 20, 40 μm) in sessile droplets, which are controlled by acoustic field-induced fluid vortex (acoustic vortex) and aggregate into clusters or rings with particles. These phenomena can be explained by the interaction of three forces, which are drag force caused by ASF, ARF caused by Leaky-SAW and varying centrifugal force. Eventually, a novel approach of free transition between the particle ring and cluster was approached via modulating the acoustic amplitude of TSAW. By this method, multilayer particles agglomerate with 20 μm wrapped around 40 μm and 20 μm wrapped around 5 μm can be obtained, which provides the possibility to dilute or concentrate the particles to a specific concentration. Full article
(This article belongs to the Special Issue Nano/Micro Technologies for Biosensors: A Themed Issue in Honor of Prof. Dr. Chung-Chiun Liu)
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16 pages, 3700 KiB  
Article
Electrochemical Biosensor Using Nitrogen-Doped Graphene/Au Nanoparticles/DNAzyme for Ca2+ Determination
by Zhixue Yu, Hui Wang, Yiguang Zhao, Fan Zhang, Xiangfang Tang and Benhai Xiong
Biosensors 2022, 12(5), 331; https://doi.org/10.3390/bios12050331 - 12 May 2022
Cited by 3 | Viewed by 2512
Abstract
An electrochemical biosensor for detecting Ca2+ concentration was proposed using glass carbon electrodes (GCEs) modified with nitrogen-doped graphene (NGR), gold nanoparticles (AuNPs) and DNAzyme. The resistance signal was amplified through two methods: electrochemical reduction of AuNPs on the NGR surface to increase [...] Read more.
An electrochemical biosensor for detecting Ca2+ concentration was proposed using glass carbon electrodes (GCEs) modified with nitrogen-doped graphene (NGR), gold nanoparticles (AuNPs) and DNAzyme. The resistance signal was amplified through two methods: electrochemical reduction of AuNPs on the NGR surface to increase the specific surface area of the electrode and strengthen the adsorption of DNAzyme; and increasement of the DNAzyme base sequence. The process of electrode modification was characterized by scanning electron microscopy, Raman spectroscopy, cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). Experimental parameters’ influence, such as the deposition time of gold nanoparticles and the detection time, were assessed by electrochemical methods. The linear ranges of the electrochemical biosensor were in the range from 5 × 10−6 to 5 × 10−5 and 5 × 10−5 to 4 × 10−4 M, with a detection limit of 3.8 × 10−6 M. The concentration of Ca2+ in the serum of dairy cows was determined by the biosensor with satisfactory results, which could be potentially used to diagnose subclinical hypocalcemia. Full article
(This article belongs to the Special Issue Nano/Micro Technologies for Biosensors: A Themed Issue in Honor of Prof. Dr. Chung-Chiun Liu)
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13 pages, 2421 KiB  
Article
Microfluidic Determination of Distinct Membrane Transport Properties between Lung Adenocarcinoma Cells CL1-0 and CL1-5
by Chiu-Jen Chen, Min-Heng Kao, Noel A. S. Alvarado, Yong-Ming Ye and Hsiu-Yang Tseng
Biosensors 2022, 12(4), 199; https://doi.org/10.3390/bios12040199 - 27 Mar 2022
Cited by 1 | Viewed by 2039
Abstract
The cell membrane permeability of a cell type to water (Lp) and cryoprotective agents (Ps), is the key factor that determines the optimal cooling and mass transportation during cryopreservation. The human lung adenocarcinoma cell line, CL1, has been widely used to study the [...] Read more.
The cell membrane permeability of a cell type to water (Lp) and cryoprotective agents (Ps), is the key factor that determines the optimal cooling and mass transportation during cryopreservation. The human lung adenocarcinoma cell line, CL1, has been widely used to study the invasive capabilities or drug resistance of lung cancer cells. Therefore, providing accurate databases of the mass transport properties of this specific cell line can be crucial for facilitating either flexible and optimal preservation, or supply. In this study, utilizing our previously proposed noncontact-based micro-vortex system, we focused on comparing the permeability phenomenon between CL1-0 and its more invasive subline, CL1-5, under several different ambient temperatures. Through the assay procedure, the cells of favor were virtually trapped in a hydrodynamic circulation to provide direct inspection using a high-speed camera, and the images were then processed to achieve the observation of a cell’s volume change with respect to time, and in turn, the permeability. Based on the noncontact nature of our system, we were able to manifest more accurate results than their contact-based counterparts, excluding errors involved in estimating the cell geometry. As the results in this experiment showed, the transport phenomena in the CL1-0 and CL1-5 cell lines are mainly composed of simple diffusion through the lipid bilayer, except for the case where CL1-5 were suspended in the cryoprotective agent (CPA) solution, which also demonstrated higher Ps values. The deviated behavior of CL1-5 might be a consequence of the altered expression of aquaporins and the coupling of a cryoprotective agent and water, and has given a vision on possible studies over these properties, and their potential relationship to invasiveness and metastatic stability of the CL1 cell line. Full article
(This article belongs to the Special Issue Nano/Micro Technologies for Biosensors: A Themed Issue in Honor of Prof. Dr. Chung-Chiun Liu)
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Review

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21 pages, 4725 KiB  
Review
Current Progress of Ratiometric Fluorescence Sensors Based on Carbon Dots in Foodborne Contaminant Detection
by Jialu Zhang, Huinan Chen, Kaidi Xu, Dongmei Deng, Qixian Zhang and Liqiang Luo
Biosensors 2023, 13(2), 233; https://doi.org/10.3390/bios13020233 - 07 Feb 2023
Cited by 9 | Viewed by 2338
Abstract
Carbon dots (CDs) are widely used in the detection of foodborne contaminants because of their biocompatibility, photoluminescence stability, and ease of chemical modification. In order to solve the interference problem of complexity in food matrices, the development of ratiometric fluorescence sensors shows great [...] Read more.
Carbon dots (CDs) are widely used in the detection of foodborne contaminants because of their biocompatibility, photoluminescence stability, and ease of chemical modification. In order to solve the interference problem of complexity in food matrices, the development of ratiometric fluorescence sensors shows great prospects. In this review, the progress of ratiometric fluorescence sensors based on CDs in foodborne contaminant detection in recent years will be summarized, focusing on the functionalized modification of CDs, the fluorescence sensing mechanism, the types of ratiometric fluorescence sensors, and the application of portable devices. In addition, the outlook on the development of the field will be presented, with the development of smartphone applications and related software helping to better enable the on-site detection of foodborne contaminants to ensure food safety and human health. Full article
(This article belongs to the Special Issue Nano/Micro Technologies for Biosensors: A Themed Issue in Honor of Prof. Dr. Chung-Chiun Liu)
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14 pages, 2630 KiB  
Review
Developments of Conventional and Microfluidic Flow Cytometry Enabling High-Throughput Characterization of Single Cells
by Minruihong Wang, Hongyan Liang, Xiao Chen, Deyong Chen, Junbo Wang, Yuan Zhang and Jian Chen
Biosensors 2022, 12(7), 443; https://doi.org/10.3390/bios12070443 - 23 Jun 2022
Cited by 12 | Viewed by 2672
Abstract
This article first reviews scientific meanings of single-cell analysis by highlighting two key scientific problems: landscape reconstruction of cellular identities during dynamic immune processes and mechanisms of tumor origin and evolution. Secondly, the article reviews clinical demands of single-cell analysis, which are complete [...] Read more.
This article first reviews scientific meanings of single-cell analysis by highlighting two key scientific problems: landscape reconstruction of cellular identities during dynamic immune processes and mechanisms of tumor origin and evolution. Secondly, the article reviews clinical demands of single-cell analysis, which are complete blood counting enabled by optoelectronic flow cytometry and diagnosis of hematologic malignancies enabled by multicolor fluorescent flow cytometry. Then, this article focuses on the developments of optoelectronic flow cytometry for the complete blood counting by comparing conventional counterparts of hematology analyzers (e.g., DxH 900 of Beckman Coulter, XN-1000 of Sysmex, ADVIA 2120i of Siemens, and CELL-DYN Ruby of Abbott) and microfluidic counterparts (e.g., microfluidic impedance and imaging flow cytometry). Future directions of optoelectronic flow cytometry are indicated where intrinsic rather than dependent biophysical parameters of blood cells must be measured, and they can replace blood smears as the gold standard of blood analysis in the near future. Full article
(This article belongs to the Special Issue Nano/Micro Technologies for Biosensors: A Themed Issue in Honor of Prof. Dr. Chung-Chiun Liu)
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