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Biosensors for the Early Diagnosis of High-Impact Human Diseases

Special Issue Editor

School of Dentistry, University of California, Los Angeles, CA, 90095, USA
Interests: liquid biopsy; NSCLC; point-of-care device; circulating tumor DNA; EFIRM platform
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Special Issue Information

Dear Colleagues,

Early diagnosis of high-impact human disease not only helps prevent disease development, but also allows individual and dynamic monitoring of these diseases, contributing to personalized medicine. Despite recent advances in biological and clinical research, many challenges remain in adapting and utilizing new biosensor technology in routine disease screening or longitudinal monitoring for early detection. The broad, unmet need for early diagnosis necessitates the development of biosensor platforms that can accurately detect a panel of multiple biomarkers at the point of care.

This Special Issue of IJMS is focused on recent progress in biosensors. Topics of interest include, but are not limited to:

  • Highly sensitive biosensor in complexing clinical context;
  • Liquid-biopsy-based biosensor for high-impact human disease;
  • Rapid and automated biosensor for sample pretreatment, detection and data analysis;
  • Biosensor platforms assisted by artificial intelligence (AI) for data interpretation, risk assessment and consequent therapeutic treatment.

Dr. Fang Wei
Guest Editor

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Keywords

  • early-stage diagnosis
  • high-impact human disease
  • biosensors
  • liquid biopsy
  • MEMs
  • point-of-care platform
  • artificial-intelligence-assisted diagnosis

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Related Special Issue

Published Papers (6 papers)

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Research

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13 pages, 2247 KiB  
Article
New Advances in Rapid Pretreatment for Small Dense LDL Cholesterol Measurement Using Shear Horizontal Surface Acoustic Wave (SH-SAW) Technology
by Tai-Hua Chou, Chia-Hsuan Cheng, Chi-Jen Lo, Guang-Huar Young, Szu-Heng Liu and Robert Y-L Wang
Int. J. Mol. Sci. 2024, 25(2), 1044; https://doi.org/10.3390/ijms25021044 - 15 Jan 2024
Cited by 2 | Viewed by 1570
Abstract
Atherosclerosis is an inflammatory disease of the arteries associated with alterations in lipid and other metabolism and is a major cause of cardiovascular disease (CVD). LDL consists of several subclasses with different sizes, densities, and physicochemical compositions. Small dense LDL (sd-LDL) is a [...] Read more.
Atherosclerosis is an inflammatory disease of the arteries associated with alterations in lipid and other metabolism and is a major cause of cardiovascular disease (CVD). LDL consists of several subclasses with different sizes, densities, and physicochemical compositions. Small dense LDL (sd-LDL) is a subclass of LDL. There is growing evidence that sd-LDL-C is associated with CVD risk, metabolic dysregulation, and several pathophysiological processes. In this study, we present a straightforward membrane device filtration method that can be performed with simple laboratory methods to directly determine sd-LDL in serum without the need for specialized equipment. The method consists of three steps: first, the precipitation of lipoproteins with magnesium harpin; second, the collection of effluent from a 100 nm filter; and third, the quantification of sd-LDL-ApoB in the effluent with an SH-SAW biosensor. There was a good correlation between ApoB values obtained using the centrifugation (y = 1.0411x + 12.96, r = 0.82, n = 20) and filtration (y = 1.0633x + 15.13, r = 0.88, n = 20) methods and commercially available sd-LDL-C assay values. In addition to the filtrate method, there was also a close correlation between sd-LDL-C and ELISA assay values (y = 1.0483x − 4489, r = 0.88, n = 20). The filtration treatment method also showed a high correlation with LDL subfractions and NMR spectra ApoB measurements (y = 2.4846x + 4.637, r = 0.89, n = 20). The presence of sd-LDL-ApoB in the effluent was also confirmed by ELISA assay. These results suggest that this filtration method is a simple and promising pretreatment for use with the SH-SAW biosensor as a rapid in vitro diagnostic (IVD) method for predicting sd-LDL concentrations. Overall, we propose a very sensitive and specific SH-SAW biosensor with the ApoB antibody in its sensitive region to monitor sd-LDL levels by employing a simple delay-time phase shifted SH-SAW device. In conclusion, based on the demonstration of our study, the SH-SAW biosensor could be a strong candidate for the future measurement of sd-LDL. Full article
(This article belongs to the Special Issue Biosensors for the Early Diagnosis of High-Impact Human Diseases)
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15 pages, 5669 KiB  
Article
A New Approach to the Quantification of Fibroblast Growth Factor 23—An Array Surface Plasmon Resonance Imaging Biosensor
by Anna Tokarzewicz, Łukasz Ołdak, Grzegorz Młynarczyk, Urszula Klekotka and Ewa Gorodkiewicz
Int. J. Mol. Sci. 2023, 24(20), 15327; https://doi.org/10.3390/ijms242015327 - 18 Oct 2023
Viewed by 1163
Abstract
A new biosensor based on the “surface plasmon resonance imaging (SPRi)” detection technique for the quantification of “fibroblast growth factor 23 (FGF23)” has been developed. FGF23 is mainly produced in bone tissues as a phosphaturic hormone that forms a trimeric complex with “fibroblast [...] Read more.
A new biosensor based on the “surface plasmon resonance imaging (SPRi)” detection technique for the quantification of “fibroblast growth factor 23 (FGF23)” has been developed. FGF23 is mainly produced in bone tissues as a phosphaturic hormone that forms a trimeric complex with “fibroblast growth factor receptor 1 (FGFR1)” and αKlotho upon secretion. FGF23 stimulates phosphate excretion and inhibits the formation of active vitamin D in the kidneys. FGF23 has been shown to play a role in bone carcinogenesis and metastasis. The newly developed method, based on the array SPRi biosensor, was validated—the precision, accuracy, and selectivity were acceptable, and yielded less than ±10% recovery. The rectilinear response of the biosensor ranges from 1 to 75 pg/mL. The limit of detection was 0.033 pg/mL, and the limit of quantification was 0.107 pg/mL. The biosensor was used to determine FGF23 concentrations in the blood plasma of healthy subjects and patients with “clear cell” renal cell carcinoma (ccRCC). The obtained results were compared with those measured through an “enzyme-linked immunosorbent assay (ELISA)”. The determined Pearson correlation coefficients were 0.994 and 0.989, demonstrating that the newly developed biosensor can be used as a competitive method for the ELISA. Full article
(This article belongs to the Special Issue Biosensors for the Early Diagnosis of High-Impact Human Diseases)
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11 pages, 3254 KiB  
Article
Single-Droplet Microsensor for Ultra-Short Circulating EFGR Mutation Detection in Lung Cancer Based on Multiplex EFIRM Liquid Biopsy
by Fang Wei, Peter Yu, Jordan Cheng, Feng Li, David Chia and David T. W. Wong
Int. J. Mol. Sci. 2023, 24(12), 10387; https://doi.org/10.3390/ijms241210387 - 20 Jun 2023
Viewed by 1962
Abstract
Liquid biopsy is a rapidly emerging field that involves the minimal/non-invasive assessment of signature somatic mutations through the analysis of circulating tumor DNA (ctDNA) shed by tumor cells in bodily fluids. Broadly speaking, the unmet need in liquid biopsy lung cancer detection is [...] Read more.
Liquid biopsy is a rapidly emerging field that involves the minimal/non-invasive assessment of signature somatic mutations through the analysis of circulating tumor DNA (ctDNA) shed by tumor cells in bodily fluids. Broadly speaking, the unmet need in liquid biopsy lung cancer detection is the lack of a multiplex platform that can detect a mutation panel of lung cancer genes using a minimum amount of sample, especially for ultra-short ctDNA (usctDNA). Here, we developed a non-PCR and non-NGS-based single-droplet-based multiplexing microsensor technology, “Electric-Field-Induced Released and Measurement (EFIRM) Liquid Biopsy” (m-eLB), for lung cancer-associated usctDNA. The m-eLB provides a multiplexable assessment of usctDNA within a single droplet of biofluid in only one well of micro-electrodes, as each electrode is coated with different probes for the ctDNA. This m-eLB prototype demonstrates accuracy for three tyrosine-kinase-inhibitor-related EGFR target sequences in synthetic nucleotides. The accuracy of the multiplexing assay has an area under the curve (AUC) of 0.98 for L858R, 0.94 for Ex19 deletion, and 0.93 for T790M. In combination, the 3 EGFR assay has an AUC of 0.97 for the multiplexing assay. Full article
(This article belongs to the Special Issue Biosensors for the Early Diagnosis of High-Impact Human Diseases)
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12 pages, 1855 KiB  
Article
Simultaneous Electrochemical Detection of LDL and MDA-LDL Using Antibody-Ferrocene or Anthraquinone Conjugates Coated Magnetic Beads
by Daria Rudewicz-Kowalczyk and Iwona Grabowska
Int. J. Mol. Sci. 2023, 24(6), 6005; https://doi.org/10.3390/ijms24066005 - 22 Mar 2023
Viewed by 2237
Abstract
The simultaneous detection of atherosclerotic cardiovascular disease (ACSVD) biomarkers was recently of great scientific interest. In this work, magnetic beads-based immunosensors for the simultaneous detection of low density lipoprotein (LDL) and malondialdehyde-modified low density lipoprotein (MDA-LDL) were presented. The approach proposed was based [...] Read more.
The simultaneous detection of atherosclerotic cardiovascular disease (ACSVD) biomarkers was recently of great scientific interest. In this work, magnetic beads-based immunosensors for the simultaneous detection of low density lipoprotein (LDL) and malondialdehyde-modified low density lipoprotein (MDA-LDL) were presented. The approach proposed was based on the formation of two types of specific immunoconjugates consisting of monoclonal antibodies: anti-LDL or anti-MDA-LDL, together with redox active molecules: ferrocene and anthraquinone, respectively, coated on magnetic beads (MBs). The decrease in redox agent current in the concentration range: 0.001–1.0 ng/mL for LDL and 0.01–10.0 ng/mL for MDA-LDL, registered by square wave voltammetry (SWV), was observed upon the creation of complex between LDL or MDA-LDL and appropriate immunoconjugates. The detection limits of 0.2 ng/mL for LDL and 0.1 ng/mL for MDA-LDL were estimated. Moreover, the results of selectivity against the possible interferents were good, as human serum albumin (HSA) and high density lipoprotein (HDL), stability and recovery studies demonstrated the potential of platform proposed for early prognosis and diagnosis of ASCVD. Full article
(This article belongs to the Special Issue Biosensors for the Early Diagnosis of High-Impact Human Diseases)
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16 pages, 4153 KiB  
Article
A Dual-Modality Imaging Method Based on Polarimetry and Second Harmonic Generation for Characterization and Evaluation of Skin Tissue Structures
by Liangyu Deng, Zhipeng Fan, Binguo Chen, Haoyu Zhai, Honghui He, Chao He, Yanan Sun, Yi Wang and Hui Ma
Int. J. Mol. Sci. 2023, 24(4), 4206; https://doi.org/10.3390/ijms24044206 - 20 Feb 2023
Cited by 7 | Viewed by 2039
Abstract
The characterization and evaluation of skin tissue structures are crucial for dermatological applications. Recently, Mueller matrix polarimetry and second harmonic generation microscopy have been widely used in skin tissue imaging due to their unique advantages. However, the features of layered skin tissue structures [...] Read more.
The characterization and evaluation of skin tissue structures are crucial for dermatological applications. Recently, Mueller matrix polarimetry and second harmonic generation microscopy have been widely used in skin tissue imaging due to their unique advantages. However, the features of layered skin tissue structures are too complicated to use a single imaging modality for achieving a comprehensive evaluation. In this study, we propose a dual-modality imaging method combining Mueller matrix polarimetry and second harmonic generation microscopy for quantitative characterization of skin tissue structures. It is demonstrated that the dual-modality method can well divide the mouse tail skin tissue specimens’ images into three layers of stratum corneum, epidermis, and dermis. Then, to quantitatively analyze the structural features of different skin layers, the gray level co-occurrence matrix is adopted to provide various evaluating parameters after the image segmentations. Finally, to quantitatively measure the structural differences between damaged and normal skin areas, an index named Q-Health is defined based on cosine similarity and the gray-level co-occurrence matrix parameters of imaging results. The experiments confirm the effectiveness of the dual-modality imaging parameters for skin tissue structure discrimination and assessment. It shows the potential of the proposed method for dermatological practices and lays the foundation for further, in-depth evaluation of the health status of human skin. Full article
(This article belongs to the Special Issue Biosensors for the Early Diagnosis of High-Impact Human Diseases)
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Review

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19 pages, 1909 KiB  
Review
The Biomedical Applications of Biomolecule Integrated Biosensors for Cell Monitoring
by Kyeongseok Song, Soon-Jin Hwang, Yangwon Jeon and Youngdae Yoon
Int. J. Mol. Sci. 2024, 25(12), 6336; https://doi.org/10.3390/ijms25126336 - 7 Jun 2024
Viewed by 822
Abstract
Cell monitoring is essential for understanding the physiological conditions and cell abnormalities induced by various stimuli, such as stress factors, microbial invasion, and diseases. Currently, various techniques for detecting cell abnormalities and metabolites originating from specific cells are employed to obtain information on [...] Read more.
Cell monitoring is essential for understanding the physiological conditions and cell abnormalities induced by various stimuli, such as stress factors, microbial invasion, and diseases. Currently, various techniques for detecting cell abnormalities and metabolites originating from specific cells are employed to obtain information on cells in terms of human health. Although the states of cells have traditionally been accessed using instrument-based analysis, this has been replaced by various sensor systems equipped with new materials and technologies. Various sensor systems have been developed for monitoring cells by recognizing biological markers such as proteins on cell surfaces, components on plasma membranes, secreted metabolites, and DNA sequences. Sensor systems are classified into subclasses, such as chemical sensors and biosensors, based on the components used to recognize the targets. In this review, we aim to outline the fundamental principles of sensor systems used for monitoring cells, encompassing both biosensors and chemical sensors. Specifically, we focus on biosensing systems in terms of the types of sensing and signal-transducing elements and introduce recent advancements and applications of biosensors. Finally, we address the present challenges in biosensor systems and the prospects that should be considered to enhance biosensor performance. Although this review covers the application of biosensors for monitoring cells, we believe that it can provide valuable insights for researchers and general readers interested in the advancements of biosensing and its further applications in biomedical fields. Full article
(This article belongs to the Special Issue Biosensors for the Early Diagnosis of High-Impact Human Diseases)
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