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Biosensors
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Biosensing and Diagnosis of Cancer
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Biosensing and Diagnosis of Cancer

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

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 32319

Special Issue Editors

Prof. Dr. Ibtisam E. Tothill

E-Mail Website1 Website2
Guest Editor
Surface Engineering and Precision Centre, Cranfield University, Cranfield, Bedfordshire MK43 0AL, UK
Interests: analytical chemistry, biosensors; nanosensors; medicinal devices; supramolecular chemistry; biomarkers; molecular diagnostics; biochips; DNA chips
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Séamus P J Higson

E-Mail Website
Guest Editor
Department of Chemical Engineering and Biotechnology, University of Cambridge, Philippa Fawcett Drive, Cambridge CB3 0AS, UK
Interests: bioanalytical chemistry and bioanalysis; point-of-care diagnostics; ultra-trace detection; bioassays; biosensors

Special Issue Information

Dear Colleagues,

Cancer remains the most feared disease and is the major cause of death worldwide.  It accounted for nearly 10 million of deaths in 2020, representing around one in six deaths according to the World Health Organization (WHO). The highest incidents of cancer are reported in breast, lung, colon and rectum, prostate, skin, and stomach. Most cancers can be cured or controlled if detected at an early stage before metastasis and are treated precisely and appropriately. Hence, early detection and diagnosis are highly effective in reducing the burden of cancer mortality. Biosensors and sensing devises can play a key role in the early detection and diagnosis of cancer. These devices can be phenomenally successful and desirable screening tools, especially as they can be either non-invasive or minimally invasive technologies. The discovery of tumor markers in body fluids has had an enormous impact on advancing cancer screening, especially outside the healthcare settings. To this end, this Special Issue will explore the use of biosensor devices in the early detection and diagnosis of different types of cancer. We invite submissions of research that help to advance the field of cancer detection using biosensors and aid in the uptake of this technology for cancer diagnosis.

With best regards,

Prof. Dr. Ibtisam E. Tothill
Prof. Dr. Séamus P J Higson
Guest Editors

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

  • biosensors
  • cancer
  • carcinoma
  • biomarkers
  • tumor markers
  • point-of-care devices
  • nanosensors
  • diagnostics
  • early-stage detection
  • rapid detection

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Published Papers (11 papers)

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Research

Jump to: Review

12 pages, 3773 KiB  
Article
Random Lasing for Bimodal Imaging and Detection of Tumor
by R. Gayathri, C. S. Suchand Sandeep, C. Vijayan and V. M. Murukeshan
Biosensors 2023, 13(12), 1003; https://doi.org/10.3390/bios13121003 - 29 Nov 2023
Cited by 2 | Viewed by 1907
Abstract
The interaction of light with biological tissues is an intriguing area of research that has led to the development of numerous techniques and technologies. The randomness inherent in biological tissues can trap light through multiple scattering events and provide optical feedback to generate [...] Read more.
The interaction of light with biological tissues is an intriguing area of research that has led to the development of numerous techniques and technologies. The randomness inherent in biological tissues can trap light through multiple scattering events and provide optical feedback to generate random lasing emission. The emerging random lasing signals carry sensitive information about the scattering dynamics of the medium, which can help in identifying abnormalities in tissues, while simultaneously functioning as an illumination source for imaging. The early detection and imaging of tumor regions are crucial for the successful treatment of cancer, which is one of the major causes of mortality worldwide. In this paper, a bimodal spectroscopic and imaging system, capable of identifying and imaging tumor polyps as small as 1 mm2, is proposed and illustrated using a phantom sample for the early diagnosis of tumor growth. The far-field imaging capabilities of the developed system can enable non-contact in vivo inspections. The integration of random lasing principles with sensing and imaging modalities has the potential to provide an efficient, minimally invasive, and cost-effective means of early detection and treatment of various diseases, including cancer. Full article
(This article belongs to the Special Issue Biosensing and Diagnosis of Cancer)
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13 pages, 2532 KiB  
Article
Improving the Accuracy of Single-Nucleotide Variant Diagnosis Using On–Off Discriminating Primers
by Juny Shin and Cheulhee Jung
Biosensors 2023, 13(3), 380; https://doi.org/10.3390/bios13030380 - 13 Mar 2023
Viewed by 2520
Abstract
Early detection of rare mutations through liquid biopsy can provide real-time information related to cancer diagnosis, prognosis, and treatment outcomes. Cell-free DNA samples used in liquid biopsies contain single-nucleotide variants (SNVs) with a variant allele frequency (VAF) of approximately ≤1%. Droplet digital polymerase [...] Read more.
Early detection of rare mutations through liquid biopsy can provide real-time information related to cancer diagnosis, prognosis, and treatment outcomes. Cell-free DNA samples used in liquid biopsies contain single-nucleotide variants (SNVs) with a variant allele frequency (VAF) of approximately ≤1%. Droplet digital polymerase chain reaction (ddPCR) is considered the gold standard of sequencing using liquid samples, generating amplicons from samples containing mutations with 0.001–0.005% VAF; however, it requires expensive equipment and time-consuming protocols. Therefore, various PCR methods for discriminating SNVs have been developed; nonetheless, non-specific amplification cannot be avoided even in the absence of mutations, which hampers the accurate diagnosis of SNVs. In this study, we introduce single-nucleotide variant on–off discrimination–PCR (Soo-PCR), a highly accurate and practical method that uses a 3′-end tailing primer for the on–off discrimination of low-abundance mutant-type targets, including SNVs. Soo-PCR minimizes the chance of incorrect judgments owing to its high discriminating power. Cancer markers, such as KRAS G12D, EGFR L858R, and EGFR T790M mutations, containing 0.1% VAF, were clearly detected in under 2 h with a high reliability comparable with that of ddPCR. This new method serves as a practical approach to accurately detect and evaluate low-abundance mutations in a user-friendly manner. Full article
(This article belongs to the Special Issue Biosensing and Diagnosis of Cancer)
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24 pages, 4979 KiB  
Article
Development of Electrochemical Immunosensors for HER-1 and HER-2 Analysis in Serum for Breast Cancer Patients
by Shayalini Wignarajah, Iva Chianella and Ibtisam E. Tothill
Biosensors 2023, 13(3), 355; https://doi.org/10.3390/bios13030355 - 7 Mar 2023
Cited by 20 | Viewed by 3448
Abstract
In this work, two human epidermal growth factor receptors, HER-1 and HER-2, were selected as biomarkers to enable the detection of breast cancer. Therefore, two biosensors were developed using gold sensor chips coupled with amperometric detection of the enzyme label horse radish peroxidase [...] Read more.
In this work, two human epidermal growth factor receptors, HER-1 and HER-2, were selected as biomarkers to enable the detection of breast cancer. Therefore, two biosensors were developed using gold sensor chips coupled with amperometric detection of the enzyme label horse radish peroxidase (HRP). The biosensors/immunosensors relied on indirect sandwich enzyme-linked immunosorbent assays with monoclonal antibodies (Ab) against HER-1 and HER-2 attached to the sensors to capture the biomarkers. Detection polyclonal antibodies followed by secondary anti-rabbit (for HER-1) and anti-goat (for HER-2) IgG antibody-HRP were then applied for signal generation. In buffer, the developed sensors showed limits of detections (LOD) of 1.06 ng mL−1 and 0.95 ng mL−1 and limits of quantification (LOQ) of 2.1 ng mL−1 and 1.5 ng mL−1 for HER-1 and HER-2, respectively. In 100% (undiluted) serum, LODs of 1.2 ng mL−1 and 1.47 ng mL−1 and LOQs of 1.5 ng mL−1 and 2.1 ng mL−1 were obtained for HER-1 and HER-2, respectively. Such limits of detections are within the serum clinical range for the two biomarkers. Furthermore, gold nanoparticles (AuNP) labelled with secondary anti-rabbit and anti-goat IgG antibody-HRP were then used to enhance the assay signal and increase the sensitivity. In buffers, LODs of 30 pg mL−1 were seen for both sensors and LOQs of 98 pg mL−1 and 35 pg mL−1 were recorded for HER-1 and HER-2, respectively. For HER-2 the AuNPs biosensor was also tested in 100% serum obtaining a LOD of 50 pg mL−1 and a LOQ of 80 pg mL−1. The HER-2 AuNP electrochemical immunosensor showed high specificity with very low cross-reactivity to HER-1. These findings demonstrate that the two developed sensors can enable early detection as well as monitoring of disease progression with a beneficial impact on patient survival and clinical outcomes. Full article
(This article belongs to the Special Issue Biosensing and Diagnosis of Cancer)
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Graphical abstract

14 pages, 3712 KiB  
Article
Detecting the PEX Like Domain of Matrix Metalloproteinase-14 (MMP-14) with Therapeutic Conjugated CNTs
by D. Vieira, J. Barralet, E. J. Harvey and G. Merle
Biosensors 2022, 12(10), 884; https://doi.org/10.3390/bios12100884 - 17 Oct 2022
Cited by 1 | Viewed by 2090
Abstract
Matrix metalloproteinases (MMPs) are essential proteins acting directly in the breakdown of the extra cellular matrix and so in cancer invasion and metastasis. Given its impact on tumor angiogenesis, monitoring MMP-14 provides strategic insights on cancer severity and treatment. In this work, we [...] Read more.
Matrix metalloproteinases (MMPs) are essential proteins acting directly in the breakdown of the extra cellular matrix and so in cancer invasion and metastasis. Given its impact on tumor angiogenesis, monitoring MMP-14 provides strategic insights on cancer severity and treatment. In this work, we report a new approach to improve the electrochemical interaction of the MMP-14 with the electrode surface while preserving high specificity. This is based on the detection of the hemopexin (PEX) domain of MMP-14, which has a greater availability with a stable and low-cost commercial molecule, as a recognition element. This molecule, called NSC-405020, is specific of the PEX domain of MMP-14 within the binding pocket. Through the covalent grafting of the NSC-405020 molecule on carbon nanotubes (CNTs), we were able to detect and quantify MMP-14 using electrochemical impedance spectroscopy with a linear range of detection of 10 ng⋅mL−1 to 100 ng⋅mL−1, and LOD of 7.5 ng⋅mL−1. The specificity of the inhibitory small molecule was validated against the PEX domain of MMP-1. The inhibitor loaded CNTs system showed as a desirable candidate to become an alternative to the conventional recognition bioelements for the detection of MMP-14. Full article
(This article belongs to the Special Issue Biosensing and Diagnosis of Cancer)
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24 pages, 6684 KiB  
Article
Non-Invasive Microwave-Based Imaging System for Early Detection of Breast Tumours
by Carolina Blanco-Angulo, Andrea Martínez-Lozano, Roberto Gutiérrez-Mazón, Carlos G. Juan, Héctor García-Martínez, Julia Arias-Rodríguez, José M. Sabater-Navarro and Ernesto Ávila-Navarro
Biosensors 2022, 12(9), 752; https://doi.org/10.3390/bios12090752 - 12 Sep 2022
Cited by 9 | Viewed by 3183
Abstract
This work introduces a microwave-based system able to detect tumours in breast phantoms in a non-invasive way. The data acquisition system is composed of a hardware system which involves high-frequency components (antennas, switches and cables), a microcontroller, a vector network analyser used as [...] Read more.
This work introduces a microwave-based system able to detect tumours in breast phantoms in a non-invasive way. The data acquisition system is composed of a hardware system which involves high-frequency components (antennas, switches and cables), a microcontroller, a vector network analyser used as measurement instrument and a computer devoted to the control and automation of the operation of the system. Concerning the software system, the computer runs a Python script which is in charge of mastering and automatising all the required stages for the data acquisition, from initialisation of the hardware system to performing and saving the measurements. We also report on the design of the high-performance broadband antenna used to carry out the measurements, as well as on the algorithm employed to build the final medical images, based on an adapted version of the so-called Improved Delay-and-Sum (IDAS) algorithm improved by a Hamming window filter and averaging preprocessing. The calibration and start-up of the system are also described. The experimental validation includes the use of different tumour models with different dielectric properties inside the breast phantom. The results show promising tumour detection capabilities, even when there is low dielectric contrast between the tumoural and healthy tissues, as is the usual case for dense breasts in young women. Full article
(This article belongs to the Special Issue Biosensing and Diagnosis of Cancer)
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14 pages, 2564 KiB  
Article
Niosome-Assisted Delivery of DNA Fluorescent Probe with Optimized Strand Displacement for Intracellular MicroRNA21 Imaging
by Zongwei Zhu, Hongqian Zhang, Xiaoxue Dong, Meng Lin and Chuanxu Yang
Biosensors 2022, 12(8), 557; https://doi.org/10.3390/bios12080557 - 24 Jul 2022
Cited by 3 | Viewed by 2413
Abstract
MicroRNAs play a vital role in cancer development and are considered as potential biomarkers for early prognostic assessment. Here, we propose a novel biosensing system to achieve fluorescence imaging of miRNA21 (miR21) in cancer cells. This system consists of two components: an optimized [...] Read more.
MicroRNAs play a vital role in cancer development and are considered as potential biomarkers for early prognostic assessment. Here, we propose a novel biosensing system to achieve fluorescence imaging of miRNA21 (miR21) in cancer cells. This system consists of two components: an optimized “off-on” double-stranded DNA (dsDNA) fluorescent for miR21 sensing by efficient strand-displacement reaction and a potent carrier vesicle, termed niosome (SPN), to facilitate the efficient intracellular delivery of the dsDNA probe. A series of dsDNA probes based on fluorescence energy resonance transfer (FRET) was assembled to target miR21. By optimizing the appropriate length of the reporter strand in the dsDNA probe, high accuracy and sensitivity for miR21 recognition are ensured. To overcome the cellular barrier, we synthesized SPN with the main components of a nonionic surfactant Span 80 and a cationic lipid DOTAP, which could efficiently load dsDNA probes via electrostatic interactions and potently deliver the dsDNA probes into cells with good biosafety. The SPN/dsDNA achieved efficient miR21 fluorescent imaging in living cells, and could discriminate cancer cells (MCF-7) from normal cells (L-02). Therefore, the proposed SPN/dsDNA system provides a powerful tool for intracellular miRNA biosensing, which holds great promise for early cancer diagnosis. Full article
(This article belongs to the Special Issue Biosensing and Diagnosis of Cancer)
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Review

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27 pages, 2576 KiB  
Review
Synthetic Receptors for Early Detection and Treatment of Cancer
by Frank Davis and Séamus P. J. Higson
Biosensors 2023, 13(11), 953; https://doi.org/10.3390/bios13110953 - 25 Oct 2023
Cited by 2 | Viewed by 2276
Abstract
Over recent decades, synthetic macrocyclic compounds have attracted interest from the scientific community due to their ability to selectively and reversibly form complexes with a huge variety of guest moieties. These molecules have been studied within a wide range of sensing and other [...] Read more.
Over recent decades, synthetic macrocyclic compounds have attracted interest from the scientific community due to their ability to selectively and reversibly form complexes with a huge variety of guest moieties. These molecules have been studied within a wide range of sensing and other fields. Within this review, we will give an overview of the most common synthetic macrocyclic compounds including cyclodextrins, calixarenes, calixresorcinarenes, pillarenes and cucurbiturils. These species all display the ability to form a wide range of complexes. This makes these compounds suitable in the field of cancer detection since they can bind to either cancer cell surfaces or indeed to marker compounds for a wide variety of cancers. The formation of such complexes allows sensitive and selective detection and quantification of such guests. Many of these compounds also show potential for the detection and encapsulation of environmental carcinogens. Furthermore, many anti-cancer drugs, although effective in in vitro tests, are not suitable for use directly for cancer treatment due to low solubility, inherent instability in in vivo environments or an inability to be adsorbed by or transported to the required sites for treatment. The reversible encapsulation of these species in a macrocyclic compound can greatly improve their solubility, stability and transport to required sites where they can be released for maximum therapeutic effect. Within this review, we intend to present the use of these species both in cancer sensing and treatment. The various macrocyclic compound families will be described, along with brief descriptions of their synthesis and properties, with an outline of their use in cancer detection and usage as therapeutic agents. Their use in the sensing of environmental carcinogens as well as their potential utilisation in the clean-up of some of these species will also be discussed. Full article
(This article belongs to the Special Issue Biosensing and Diagnosis of Cancer)
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18 pages, 1644 KiB  
Review
Circulating Tumor Cells Adhesion: Application in Biosensors
by Eduarda B. Paglia, Estela K. K. Baldin, Gabriela P. Freitas, Thalyta S. A. Santiago, João B. M. R. Neto, Jorge V. L. Silva, Hernandes F. Carvalho and Marisa M. Beppu
Biosensors 2023, 13(9), 882; https://doi.org/10.3390/bios13090882 - 12 Sep 2023
Cited by 2 | Viewed by 1867
Abstract
The early and non-invasive diagnosis of tumor diseases has been widely investigated by the scientific community focusing on the development of sensors/biomarkers that act as a way of recognizing the adhesion of circulating tumor cells (CTCs). As a challenge in this area, strategies [...] Read more.
The early and non-invasive diagnosis of tumor diseases has been widely investigated by the scientific community focusing on the development of sensors/biomarkers that act as a way of recognizing the adhesion of circulating tumor cells (CTCs). As a challenge in this area, strategies for CTCs capture and enrichment currently require improvements in the sensors/biomarker’s selectivity. This can be achieved by understanding the biological recognition factors for different cancer cell lines and also by understanding the interaction between surface parameters and the affinity between macromolecules and the cell surface. To overcome some of these concerns, electrochemical sensors have been used as precise, fast-response, and low-cost transduction platforms for application in cytosensors. Additionally, distinct materials, geometries, and technologies have been investigated to improve the sensitivity and specificity properties of the support electrode that will transform biochemical events into electrical signals. This review identifies novel approaches regarding the application of different specific biomarkers (CD44, Integrins, and EpCAm) for capturing CTCs. These biomarkers can be applied in electrochemical biosensors as a cytodetection strategy for diagnosis of cancerous diseases. Full article
(This article belongs to the Special Issue Biosensing and Diagnosis of Cancer)
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29 pages, 3197 KiB  
Review
A Comprehensive Review on Electrochemical Nano Biosensors for Precise Detection of Blood-Based Oncomarkers in Breast Cancer
by Mahdi Sadeghi, Somayeh Sadeghi, Seyed Morteza Naghib and Hamid Reza Garshasbi
Biosensors 2023, 13(4), 481; https://doi.org/10.3390/bios13040481 - 16 Apr 2023
Cited by 7 | Viewed by 3355
Abstract
Breast cancer (BC), one of the most common and life-threatening cancers, has the highest incidence rate among women. Early diagnosis of BC oncomarkers is considered the most effective strategy for detecting and treating BC. Finding the type and stage of BC in women [...] Read more.
Breast cancer (BC), one of the most common and life-threatening cancers, has the highest incidence rate among women. Early diagnosis of BC oncomarkers is considered the most effective strategy for detecting and treating BC. Finding the type and stage of BC in women as soon as possible is one of the greatest ways to stop its incidence and negative effects on medical treatment. The development of biosensors for early, sensitive, and selective detection of oncomarkers has recently attracted much attention. An electrochemical nano biosensor (EN) is a very suitable option for a powerful tool for cancer diagnosis. This comprehensive review provides information about the prevalence and pathobiology of BC, recent advances in clinically available BC oncomarkers, and the most common electrochemical nano biosensors for point-of-care (POC) detection of various BC oncomarkers using nanomaterial-based signal amplification techniques. Full article
(This article belongs to the Special Issue Biosensing and Diagnosis of Cancer)
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22 pages, 4791 KiB  
Review
Current Advances in Technologies for Single Extracellular Vesicle Analysis and Its Clinical Applications in Cancer Diagnosis
by Lei Qiu, Xingzhu Liu, Libo Zhu, Liqiang Luo, Na Sun and Renjun Pei
Biosensors 2023, 13(1), 129; https://doi.org/10.3390/bios13010129 - 12 Jan 2023
Cited by 10 | Viewed by 4401
Abstract
Extracellular vesicles (EVs) have been regarded as one of the most potential diagnostic biomarkers for different cancers, due to their unique physiological and pathological functions. However, it is still challenging to precisely analyze the contents and sources of EVs, due to their heterogeneity. [...] Read more.
Extracellular vesicles (EVs) have been regarded as one of the most potential diagnostic biomarkers for different cancers, due to their unique physiological and pathological functions. However, it is still challenging to precisely analyze the contents and sources of EVs, due to their heterogeneity. Herein, we summarize the advances in technologies for a single EV analysis, which may provide new strategies to study the heterogeneity of EVs, as well as their cargo, more specifically. Furthermore, the applications of a single EV analysis on cancer early diagnosis are also discussed. Full article
(This article belongs to the Special Issue Biosensing and Diagnosis of Cancer)
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37 pages, 3163 KiB  
Review
2D Hetero-Nanoconstructs of Black Phosphorus for Breast Cancer Theragnosis: Technological Advancements
by Soji Soman, Sanjay Kulkarni, Abhijeet Pandey, Namdev Dhas, Suresh Subramanian, Archana Mukherjee and Srinivas Mutalik
Biosensors 2022, 12(11), 1009; https://doi.org/10.3390/bios12111009 - 11 Nov 2022
Cited by 10 | Viewed by 3252
Abstract
As per global cancer statistics of 2020, female breast cancer is the most commonly diagnosed cancer and also the foremost cause of cancer death in women. Traditional treatments include a number of negative effects, making it necessary to investigate novel smart drug delivery [...] Read more.
As per global cancer statistics of 2020, female breast cancer is the most commonly diagnosed cancer and also the foremost cause of cancer death in women. Traditional treatments include a number of negative effects, making it necessary to investigate novel smart drug delivery methods and identify new therapeutic approaches. Efforts for developing novel strategies for breast cancer therapy are being devised worldwide by various research groups. Currently, two-dimensional black phosphorus nanosheets (BPNSs) have attracted considerable attention and are best suited for theranostic nanomedicine. Particularly, their characteristics, including drug loading efficacy, biocompatibility, optical, thermal, electrical, and phototherapeutic characteristics, support their growing demand as a potential substitute for graphene-based nanomaterials in biomedical applications. In this review, we have explained different platforms of BP nanomaterials for breast cancer management, their structures, functionalization approaches, and general methods of synthesis. Various characteristics of BP nanomaterials that make them suitable for cancer therapy and diagnosis, such as large surface area, nontoxicity, solubility, biodegradability, and excellent near-infrared (NIR) absorption capability, are discussed in the later sections. Next, we summarize targeting approaches using various strategies for effective therapy with BP nanoplatforms. Then, we describe applications of BP nanomaterials for breast cancer treatment, which include drug delivery, codelivery of drugs, photodynamic therapy, photothermal therapy, combined therapy, gene therapy, immunotherapy, and multidrug resistance reversal strategy. Finally, the present challenges and future aspects of BP nanomaterials are discussed. Full article
(This article belongs to the Special Issue Biosensing and Diagnosis of Cancer)
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