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Fluorescence Sensors for Biological and Medical Applications

A special issue of Sensors (ISSN 1424-8220). This special issue belongs to the section "Biosensors".

Deadline for manuscript submissions: 25 March 2025 | Viewed by 11218

Special Issue Editor

Dr. Jiangwei Tian

E-Mail Website
Guest Editor
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China
Interests: biosensors; molecular probes

Special Issue Information

Dear Colleagues,

Nature has used biosensing since time immemorial, using sensory neurons in the nose to detect odors and those in the tongue to taste dissolved substances. Our understanding of how biological organisms detect trace amounts of biochemicals in complex systems has evolved over time. Recently, fluorescence sensors have been extensively used in various fields such as life science, medical diagnosis and the development of new drugs because of their high sensitivity, better selectivity, rapid and easy response, and less reliance on instruments.

This Special Issue therefore aims to put together original research and review articles on recent advances, technologies, solutions, applications, and new challenges in the field of fluorescence sensors.

Potential topics include but are not limited to:

  • Construction of new fluorescence sensors
  • Fluorescence sensors for high-throughput screening
  • Fluorescence sensors in the detection of disease markers
  • Fluorescence sensors in the detection of disease progression
  • New application of fluorescence sensors in the biomedicine field
  • Fluorescent sensors combined with biological big data and artificial intelligence

Dr. Jiangwei Tian
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.

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Published Papers (8 papers)

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Research

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21 pages, 3542 KiB  
Article
Challenges and Solutions for Leave-One-Out Biosensor Design in the Context of a Rugged Fitness Landscape
by Shounak Banerjee, Keith Fraser, Donna E. Crone, Jinal C. Patel, Sarah E. Bondos and Christopher Bystroff
Sensors 2024, 24(19), 6380; https://doi.org/10.3390/s24196380 - 1 Oct 2024
Viewed by 672
Abstract
The leave-one-out (LOO) green fluorescent protein (GFP) approach to biosensor design combines computational protein design with split protein reconstitution. LOO-GFPs reversibly fold and gain fluorescence upon encountering the target peptide, which can be redefined by computational design of the LOO site. Such an [...] Read more.
The leave-one-out (LOO) green fluorescent protein (GFP) approach to biosensor design combines computational protein design with split protein reconstitution. LOO-GFPs reversibly fold and gain fluorescence upon encountering the target peptide, which can be redefined by computational design of the LOO site. Such an approach can be used to create reusable biosensors for the early detection of emerging biological threats. Enlightening biophysical inferences for nine LOO-GFP biosensor libraries are presented, with target sequences from dengue, influenza, or HIV, replacing beta strands 7, 8, or 11. An initially low hit rate was traced to components of the energy function, manifesting in the over-rewarding of over-tight side chain packing. Also, screening by colony picking required a low library complexity, but designing a biosensor against a peptide of at least 12 residues requires a high-complexity library. This double-bind was solved using a “piecemeal” iterative design strategy. Also, designed LOO-GFPs fluoresced in the unbound state due to unwanted dimerization, but this was solved by fusing a fully functional prototype LOO-GFP to a fiber-forming protein, Drosophila ultrabithorax, creating a biosensor fiber. One influenza hemagglutinin biosensor is characterized here in detail, showing a shifted excitation/emission spectrum, a micromolar affinity for the target peptide, and an unexpected photo-switching ability. Full article
(This article belongs to the Special Issue Fluorescence Sensors for Biological and Medical Applications)
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18 pages, 3436 KiB  
Article
Polycations as Aptamer-Binding Modulators for Sensitive Fluorescence Anisotropy Assay of Aflatoxin B1
by Alexey V. Samokhvalov, Alena A. Mironova, Sergei A. Eremin, Anatoly V. Zherdev and Boris B. Dzantiev
Sensors 2024, 24(10), 3230; https://doi.org/10.3390/s24103230 - 19 May 2024
Cited by 1 | Viewed by 1193
Abstract
Fluorescence induced by the excitation of a fluorophore with plane-polarized light has a different polarization depending on the size of the fluorophore-containing reagent and the rate of its rotation. Based on this effect, many analytical systems have been implemented in which an analyte [...] Read more.
Fluorescence induced by the excitation of a fluorophore with plane-polarized light has a different polarization depending on the size of the fluorophore-containing reagent and the rate of its rotation. Based on this effect, many analytical systems have been implemented in which an analyte contained in a sample and labeled with a fluorophore (usually fluorescein) competes to bind to antibodies. Replacing antibodies in such assays with aptamers, low-cost and stable oligonucleotide receptors, is complicated because binding a fluorophore to them causes a less significant change in the polarization of emissions. This work proposes and characterizes the compounds of the reaction medium that improve analyte binding and reduce the mobility of the aptamer–fluorophore complex, providing a higher analytical signal and a lower detection limit. This study was conducted on aflatoxin B1 (AFB1), a ubiquitous toxicant contaminating foods of plant origins. Eight aptamers specific to AFB1 with the same binding site and different regions stabilizing their structures were compared for affinity, based on which the aptamer with 38 nucleotides in length was selected. The polymers that interact reversibly with oligonucleotides, such as poly-L-lysine and polyethylene glycol, were tested. It was found that they provide the desired reduction in the depolarization of emitted light as well as high concentrations of magnesium cations. In the selected optimal medium, AFB1 detection reached a limit of 1 ng/mL, which was 12 times lower than in the tris buffer commonly used for anti-AFB1 aptamers. The assay time was 30 min. This method is suitable for controlling almond samples according to the maximum permissible levels of their contamination by AFB1. The proposed approach could be applied to improve other aptamer-based analytical systems. Full article
(This article belongs to the Special Issue Fluorescence Sensors for Biological and Medical Applications)
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28 pages, 5296 KiB  
Article
Unveiling Morphine: A Rapid and Selective Fluorescence Sensor for Forensic and Medical Analysis
by Ramin Boroujerdi, Andrew Butt, Richard Paul and Santanu Majumder
Sensors 2024, 24(6), 1722; https://doi.org/10.3390/s24061722 - 7 Mar 2024
Cited by 1 | Viewed by 2070
Abstract
Opioid use, particularly morphine, is linked to CNS-related disorders, comorbidities, and premature death. Morphine, a widely abused opioid, poses a significant global health threat and serves as a key metabolite in various opioids. Here, we present a turn-off fluorescent sensor capable of detecting [...] Read more.
Opioid use, particularly morphine, is linked to CNS-related disorders, comorbidities, and premature death. Morphine, a widely abused opioid, poses a significant global health threat and serves as a key metabolite in various opioids. Here, we present a turn-off fluorescent sensor capable of detecting morphine with exceptional sensitivity and speed in various samples. The fluorescent sensor was developed through the dimerization process of 7-methoxy-1-tetralone and subsequent demethylation to produce the final product. Despite morphine possessing inherent fluorophoric properties and emitting light in an approximately similar wavelength as the sensor’s fluorescent blue light, the introduction of the target molecule (morphine) in the presence of the sensor caused a reduction in the sensor’s fluorescence intensity, which is attributable to the formation of the sensor–morphine complex. By utilizing this fluorescence quenching sensor, the chemo-selective detection of morphine becomes highly feasible, encompassing a linear range from 0.008 to 40 ppm with an impressive limit of detection of 8 ppb. Consequently, this molecular probe demonstrates a successful application in determining trace amounts of morphine within urine, yielding satisfactory analytical results. The study also explores the effect of several variables on the sensor’s response and optimizes the detection of morphine in urine using a response surface methodology with a central composite design. Full article
(This article belongs to the Special Issue Fluorescence Sensors for Biological and Medical Applications)
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13 pages, 2418 KiB  
Article
In Situ Synthesis of Highly Fluorescent, Phosphorus-Doping Carbon-Dot-Functionalized, Dendritic Silica Nanoparticles Applied for Multi-Component Lateral Flow Immunoassay
by Jia-Xuan Hu and Shou-Nian Ding
Sensors 2024, 24(1), 19; https://doi.org/10.3390/s24010019 - 19 Dec 2023
Cited by 1 | Viewed by 1501
Abstract
The sensitivity of fluorescent lateral flow immunoassay (LFIA) test strips is compromised by the low fluorescence intensity of the signaling molecules. In this study, we synthesized novel phosphorus-doped carbon-dot-based dendritic mesoporous silica nanoparticles (DMSNs-BCDs) with a quantum yield as high as 93.7% to [...] Read more.
The sensitivity of fluorescent lateral flow immunoassay (LFIA) test strips is compromised by the low fluorescence intensity of the signaling molecules. In this study, we synthesized novel phosphorus-doped carbon-dot-based dendritic mesoporous silica nanoparticles (DMSNs-BCDs) with a quantum yield as high as 93.7% to break this bottleneck. Meanwhile, the in situ growth method increased the loading capacity of carbon dots on dendritic mesoporous silica, effectively enhancing the fluorescence intensity of the composite nanospheres. Applied DMSNs-BCDs in LFIA can not only semi-quantitatively detect a single component in a short time frame (procalcitonin (PCT), within 15 min) but also detect the dual components with a low limit of detection (LOD) (carbohydrate antigen 199 (CA199) LOD: 1 U/mL; alpha-fetoprotein (AFP) LOD: 0.01 ng/mL). And the LOD of PCT detection (0.01 ng/mL) is lower by 1.7 orders of magnitude compared to conventional colloidal gold strips. For CA199, the LOD is reduced by a factor of four compared to LFIA using gold nanoparticles as substrates, and for AFP, the LOD is lowered by two orders of magnitude compared to colloidal gold LFIA. Furthermore, the coefficients of variation (CV) for intra-assay and inter-assay measurements are both less than 11%. Full article
(This article belongs to the Special Issue Fluorescence Sensors for Biological and Medical Applications)
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Graphical abstract

16 pages, 3219 KiB  
Article
A Multichannel Fluorescent Array Sensor for Discrimination of Different Types of Drug-Induced Kidney Injury
by Kunhui Sun, Bing Wang, Jiaoli Lin, Lei Han, Meifang Li, Ping Wang, Xiean Yu and Jiangwei Tian
Sensors 2023, 23(13), 6114; https://doi.org/10.3390/s23136114 - 3 Jul 2023
Cited by 2 | Viewed by 1433
Abstract
The differences in urinary proteins could provide a novel opportunity to distinguish the different types of drug-induced kidney injury (DIKI). In this research, Au nanoparticles–polyethyleneimine (AuNPs–PEI) and the three fluorophore-labeled proteins (FLPs) have been constructed as a multichannel fluorescent array sensor via electrostatic [...] Read more.
The differences in urinary proteins could provide a novel opportunity to distinguish the different types of drug-induced kidney injury (DIKI). In this research, Au nanoparticles–polyethyleneimine (AuNPs–PEI) and the three fluorophore-labeled proteins (FLPs) have been constructed as a multichannel fluorescent array sensor via electrostatic interaction, which was used to detect the subtle changes in urine collected from the pathological state of DIKI. Once the urine from different types of DIKI was introduced, the binding equilibrium between AuNPs–PEI and FLPs would be broken due to the competitive binding of urinary protein, and the corresponding fluorescence response pattern would be generated. Depending on the different fluorescence response patterns, the different types of DIKI were successfully identified by principal component analysis (PCA) and linear discriminant analysis (LDA). Accordingly, the strategy was expected to be a powerful technique for evaluating the potential unclear mechanisms of nephrotoxic drugs, which would provide a promising method for screening potential renal-protective drugs. Full article
(This article belongs to the Special Issue Fluorescence Sensors for Biological and Medical Applications)
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Graphical abstract

12 pages, 5896 KiB  
Article
Thin and Scalable Hybrid Emission Filter via Plasma Etching for Low-Invasive Fluorescence Detection
by Erus Rustami, Kiyotaka Sasagawa, Kenji Sugie, Yasumi Ohta, Hironari Takehara, Makito Haruta, Hiroyuki Tashiro and Jun Ohta
Sensors 2023, 23(7), 3695; https://doi.org/10.3390/s23073695 - 3 Apr 2023
Cited by 3 | Viewed by 1848
Abstract
Hybrid emission filters, comprising an interference filter and an absorption filter, exhibit high excitation light rejection performance and can act as lensless fluorescent devices. However, it has been challenging to produce them in large batches over a large area. In this study, we [...] Read more.
Hybrid emission filters, comprising an interference filter and an absorption filter, exhibit high excitation light rejection performance and can act as lensless fluorescent devices. However, it has been challenging to produce them in large batches over a large area. In this study, we propose and demonstrate a method for transferring a Si substrate, on which the hybrid filter is deposited, onto an image sensor by attaching it to the sensor and removing the substrate via plasma etching. Through this method, we can transfer uniform filters onto fine micrometer-sized needle devices and millimeter-sized multisensor chips. Optical evaluation reveals that the hybrid filter emits light in the 500 to 560 nm range, close to the emission region of green fluorescent protein (GFP). Furthermore, by observing the fluorescence emission from the microbeads, a spatial resolution of 12.11 μm is calculated. In vitro experiments confirm that the fabricated device is able to discriminate GFP emission patterns from brain slices. Full article
(This article belongs to the Special Issue Fluorescence Sensors for Biological and Medical Applications)
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Review

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36 pages, 15898 KiB  
Review
Recent Advances in Calixarene-Based Fluorescent Sensors for Biological Applications
by Paula M. Marcos and Mário N. Berberan-Santos
Sensors 2024, 24(22), 7181; https://doi.org/10.3390/s24227181 - 8 Nov 2024
Viewed by 631
Abstract
Due to their structural features, macrocyclic compounds such as calixarenes, conjugated with a variety of fluorophores have led to the development of fluorescent probes for numerous applications. This review covers the recent advances (from 2009 to date) made in calixarene-based fluorescent sensors and [...] Read more.
Due to their structural features, macrocyclic compounds such as calixarenes, conjugated with a variety of fluorophores have led to the development of fluorescent probes for numerous applications. This review covers the recent advances (from 2009 to date) made in calixarene-based fluorescent sensors and their biological applications. In addition to the fluorescence mechanisms used to signal the analyte binding, this article focuses mainly on the detection of biological relevant ions, on the selective sensing of biomolecules, such as amino acids, enzymes, drugs and other organic compounds, and on intracellular imaging. Calixarene-containing fluorescent nanoparticles and nanoaggregates for imaging and drug delivery are also described. Finally, this review presents some conclusions and future perspectives in this field. Full article
(This article belongs to the Special Issue Fluorescence Sensors for Biological and Medical Applications)
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30 pages, 4821 KiB  
Review
Molecularly Imprinted Ratiometric Fluorescent Sensors for Analysis of Pharmaceuticals and Biomarkers
by Jingyi Yan, Siwu Liu, Dani Sun, Siyuan Peng, Yongfei Ming, Abbas Ostovan, Zhihua Song, Jinmao You, Jinhua Li and Huaying Fan
Sensors 2024, 24(21), 7068; https://doi.org/10.3390/s24217068 - 2 Nov 2024
Viewed by 1057
Abstract
Currently, analyzing pharmaceuticals and biomarkers is crucial for ensuring medication safety and protecting life and health, and there is an urgent need to develop new and efficient analytical techniques in view of the limitations of traditional analytical methods. Molecularly imprinted ratiometric fluorescent (MI-RFL) [...] Read more.
Currently, analyzing pharmaceuticals and biomarkers is crucial for ensuring medication safety and protecting life and health, and there is an urgent need to develop new and efficient analytical techniques in view of the limitations of traditional analytical methods. Molecularly imprinted ratiometric fluorescent (MI-RFL) sensors have received increasing attention in the field of analytical detection due to their high selectivity, sensitivity and anti-interference ability, short response time, and visualization. This review summarizes the recent advances of MI-RFL sensors in the field of pharmaceuticals and biomarkers detection. Firstly, the fluorescence sources and working mechanisms of MI-RFL sensors are briefly introduced. On this basis, new techniques and strategies for preparing molecularly imprinted polymers, such as dummy template imprinting, nanoimprinting, multi-template imprinting, and stimulus-responsive imprinting strategies, are presented. Then, dual- and triple-emission types of fluorescent sensors are introduced. Subsequently, specific applications of MI-RFL sensors in pharmaceutical analysis and biomarkers detection are highlighted. In addition, innovative applications of MI-RFL sensors in point-of-care testing are discussed in-depth. Finally, the challenges of MI-RFL sensors for analysis of pharmaceuticals and biomarkers are proposed, and the research outlook and development trends of MI-RFL sensors are prospected. Full article
(This article belongs to the Special Issue Fluorescence Sensors for Biological and Medical Applications)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: A multichannel fluorescent array sensor for discrimination of different types of drug–induced kidney injury
Authors: Kunhui Sun; Bing Wang; Jiaoli Lin; Lei Han; Meifang Li; Ping Wang; Xie-an Yu; Jiangwei Tian
Affiliation: a State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, P.R. China. b NMPA Key Laboratory for Bioequivalence Research of Generic Drug Evaluation, Shenzhen Institute for Drug Control, Shenzhen 518057, China
Abstract: The difference in urinary protein could provide a novel opportunity to distinguish the different injury types of drug–induced kidney injury (DIKI). In this research, Au nanoparticles–polyethyleneimine (AuNPs–PEI) and the three fluorophore–labeled proteins (FLPs) has been constructed as a multichannel fluorescent array sensor via electrostatic interaction, which was used to detect the subtle changes in urinary proteins under the pathological state of DIKI. Once the urine from different injury types of DIKI was introduced, the binding equilibrium between AuNPs–PEI and FLPs would be broken due to the competitive binding of urinary protein with the sensor and the corresponding fluorescence response pattern would be generated. Furtherly, depending on the different fluorescence response pattern, the different injury types of DIKI were successfully identified by principal component analysis (PCA) and linear discriminant analysis (LDA). Accordingly, the strategy was expected to be a powerful technique for evaluating the potential unclear mechanisms of nephrotoxic drugs, which would provide a promising method for further screening potential renal protective drugs.

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