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Enabling Technologies for Biosensors

A topical collection in Sensors (ISSN 1424-8220). This collection belongs to the section "Biosensors".

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Editors

Consiglio Nazionale delle Ricerche, Institute of Biophysics, Genova, Italy
Interests: bioelectrochemistry; electrodes; self-assembled monolayers; nanoscience; nanomaterials; nanoparticle synthesis; electrochemical detection; surface functionalization; surface characterization; cyclic voltammetry; surface electrochemistry; quartz crystal microbalance; electron transfer in DNA and proteins; electrochemical quartz crystal microbalance
CNR-Nanoscience Institute-S3, Via Campi 213/A, 41125 Modena, Italy
Interests: bioelectrochemistry; electrodes; self-assembled monolayers; nanoscience; nanomaterials; nanoparticle synthesis; electrochemical detection; surface functionalization; surface characterization; cyclic voltammetry; surface electrochemistry; quartz crystal microbalance; electron transfer in DNA and proteins; electrochemical quartz crystal microbalance

Topical Collection Information

Dear Colleagues,

Biosensors are devices endowed with the ability of sensing and quantifying the presence of molecules of biological origin, possibly utilizing also biological molecules to probe some analytes either in vivo or in vitro.

These devices are systems often requiring the integration of different, mutually interacting stages to come up with an operating sensor.

Sample preparation, sample translation, analyte exposure to sensing elements, signal transduction, amplification, data acquisition and storage, data readout and evaluation are only some examples of needed stages.

As such, biosensors rely on both well established and developing technologies such as micro to nanoelectronics, optics, microfluidics, (electro)chemistry, diverse biotechnologies (PCR, protein engineering, protein heterologous overexpression, phage display, solid state peptide synthesis…), combinatorial chemistry, surface functionalization, AI, just to quote some.

All these aspects can be regarded as enabling technologies relevant to the implementation of biosensors.

Therefore, this Topical Collection aims to collect the latest scientific and technological advances in any relevant enabling technology impinging on the development and improvement of biosensors.

Both research papers and critical reviews are welcome on the following non- exhaustive list of topics:

  • surface (bio)functionalization
  • surface physical-chemical conditioning
  • micro-nanoelectronics for biosensors
  • transduction mechanisms
  • microfluidics
  • sample preparation
  • sample handling and translation
  • sensing and transduction techniques
  • biomolecular engineering for biosensors
  • biosensor arrays and parallelization

Prof. Dr. Paolo Facci
Prof. Dr. Andrea Alessandrini
Collection 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 collection 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. Sensors is an international peer-reviewed open access semimonthly 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 2600 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.

Published Papers (7 papers)

2022

Jump to: 2021, 2020

17 pages, 37136 KiB  
Article
Force Sensing on Cells and Tissues by Atomic Force Microscopy
by Hatice Holuigue, Ewelina Lorenc, Matteo Chighizola, Carsten Schulte, Luca Varinelli, Marcello Deraco, Marcello Guaglio, Manuela Gariboldi and Alessandro Podestà
Sensors 2022, 22(6), 2197; https://doi.org/10.3390/s22062197 - 11 Mar 2022
Cited by 10 | Viewed by 3882
Abstract
Biosensors are aimed at detecting tiny physical and chemical stimuli in biological systems. Physical forces are ubiquitous, being implied in all cellular processes, including cell adhesion, migration, and differentiation. Given the strong interplay between cells and their microenvironment, the extracellular matrix (ECM) and [...] Read more.
Biosensors are aimed at detecting tiny physical and chemical stimuli in biological systems. Physical forces are ubiquitous, being implied in all cellular processes, including cell adhesion, migration, and differentiation. Given the strong interplay between cells and their microenvironment, the extracellular matrix (ECM) and the structural and mechanical properties of the ECM play an important role in the transmission of external stimuli to single cells within the tissue. Vice versa, cells themselves also use self-generated forces to probe the biophysical properties of the ECM. ECM mechanics influence cell fate, regulate tissue development, and show peculiar features in health and disease conditions of living organisms. Force sensing in biological systems is therefore crucial to dissecting and understanding complex biological processes, such as mechanotransduction. Atomic Force Microscopy (AFM), which can both sense and apply forces at the nanoscale, with sub-nanonewton sensitivity, represents an enabling technology and a crucial experimental tool in biophysics and mechanobiology. In this work, we report on the application of AFM to the study of biomechanical fingerprints of different components of biological systems, such as the ECM, the whole cell, and cellular components, such as the nucleus, lamellipodia and the glycocalyx. We show that physical observables such as the (spatially resolved) Young’s Modulus (YM) of elasticity of ECMs or cells, and the effective thickness and stiffness of the glycocalyx, can be quantitatively characterized by AFM. Their modification can be correlated to changes in the microenvironment, physio-pathological conditions, or gene regulation. Full article
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12 pages, 2103 KiB  
Article
Magnetic Nanoparticles Enhanced Surface Plasmon Resonance Biosensor for Rapid Detection of Salmonella Typhimurium in Romaine Lettuce
by Devendra Bhandari, Fur-Chi Chen and Roger C. Bridgman
Sensors 2022, 22(2), 475; https://doi.org/10.3390/s22020475 - 09 Jan 2022
Cited by 14 | Viewed by 2397
Abstract
Salmonella is one of the major foodborne pathogens responsible for many cases of illnesses, hospitalizations and deaths worldwide. Although different methods are available to timely detect Salmonella in foods, surface plasmon resonance (SPR) has the benefit of real-time detection with a high sensitivity [...] Read more.
Salmonella is one of the major foodborne pathogens responsible for many cases of illnesses, hospitalizations and deaths worldwide. Although different methods are available to timely detect Salmonella in foods, surface plasmon resonance (SPR) has the benefit of real-time detection with a high sensitivity and specificity. The purpose of this study was to develop an SPR method in conjunction with magnetic nanoparticles (MNPs) for the rapid detection of Salmonella Typhimurium. The assay utilizes a pair of well-characterized, flagellin-specific monoclonal antibodies; one is immobilized on the sensor surface and the other is coupled to the MNPs. Samples of romaine lettuce contaminated with Salmonella Typhimurium were washed with deionized water, and bacterial cells were captured on a filter membrane by vacuum filtration. SPR assays were compared in three different formats—direct assay, sequential two-step sandwich assay, and preincubation one-step sandwich assay. The interaction of flagellin and MNPs with the antibody-immobilized sensor surface were analyzed. SPR signals from a sequential two-step sandwich assay and preincubation one-step sandwich assay were 7.5 times and 14.0 times higher than the direct assay. The detection limits of the assay were 4.7 log cfu/mL in the buffer and 5.2 log cfu/g in romaine lettuce samples. Full article
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2021

Jump to: 2022, 2020

21 pages, 4252 KiB  
Article
Polyoxazolines with a Vicinally Double-Bioactivated Terminus for Biomacromolecular Affinity Assessment
by Florian Pinzner, Thorsten Keller, Jürgen Mut, Julian Bechold, Jürgen Seibel and Jürgen Groll
Sensors 2021, 21(9), 3153; https://doi.org/10.3390/s21093153 - 01 May 2021
Cited by 2 | Viewed by 2164
Abstract
Interactions between proteins and carbohydrates with larger biomacromolecules, e.g., lectins, are usually examined using self-assembled monolayers on target gold surfaces as a simplified model measuring setup. However, most of those measuring setups are either limited to a single substrate or do not allow [...] Read more.
Interactions between proteins and carbohydrates with larger biomacromolecules, e.g., lectins, are usually examined using self-assembled monolayers on target gold surfaces as a simplified model measuring setup. However, most of those measuring setups are either limited to a single substrate or do not allow for control over ligand distance and spacing. Here, we develop a synthetic strategy, consisting of a cascade of a thioesterification, native chemical ligation (NCL) and thiol-ene reaction, in order to create three-component polymer conjugates with a defined double bioactivation at the chain end. The target architecture is the vicinal attachment of two biomolecule residues to the α telechelic end point of a polymer and a thioether group at the ω chain end for fixating the conjugate to a gold sensor chip surface. As proof-of-principle studies for affinity measurements, we demonstrate the interaction between covalently bound mannose and ConA in surface acoustic wave (SAW) and surface plasmon resonance (SPR) experiments. Full article
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27 pages, 2621 KiB  
Review
An Overview on Microfluidic Systems for Nucleic Acids Extraction from Human Raw Samples
by Daniele Obino, Massimo Vassalli, Alberto Franceschi, Andrea Alessandrini, Paolo Facci and Federica Viti
Sensors 2021, 21(9), 3058; https://doi.org/10.3390/s21093058 - 27 Apr 2021
Cited by 25 | Viewed by 7488
Abstract
Nucleic acid (NA) extraction is a basic step for genetic analysis, from scientific research to diagnostic and forensic applications. It aims at preparing samples for its application with biomolecular technologies such as isothermal and non-isothermal amplification, hybridization, electrophoresis, Sanger sequencing and next-generation sequencing. [...] Read more.
Nucleic acid (NA) extraction is a basic step for genetic analysis, from scientific research to diagnostic and forensic applications. It aims at preparing samples for its application with biomolecular technologies such as isothermal and non-isothermal amplification, hybridization, electrophoresis, Sanger sequencing and next-generation sequencing. Multiple steps are involved in NA collection from raw samples, including cell separation from the rest of the specimen, cell lysis, NA isolation and release. Typically, this process needs molecular biology facilities, specialized instrumentation and labor-intensive operations. Microfluidic devices have been developed to analyze NA samples with high efficacy and sensitivity. In this context, the integration within the chip of the sample preparation phase is crucial to leverage the promise of portable, fast, user-friendly and economic point-of-care solutions. This review presents an overview of existing lab-on-a-chip (LOC) solutions designed to provide automated NA extraction from human raw biological fluids, such as whole blood, excreta (urine and feces), saliva. It mainly focuses on LOC implementation aspects, aiming to describe a detailed panorama of strategies implemented for different human raw sample preparations. Full article
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19 pages, 2872 KiB  
Article
Label-Free Protein Detection by Micro-Acoustic Biosensor Coupled with Electrical Field Sorting. Theoretical Study in Urine Models
by Nikolay Mukhin, Georgii Konoplev, Aleksandr Oseev, Marc-Peter Schmidt, Oksana Stepanova, Andrey Kozyrev, Alexander Dmitriev and Soeren Hirsch
Sensors 2021, 21(7), 2555; https://doi.org/10.3390/s21072555 - 06 Apr 2021
Cited by 6 | Viewed by 3471
Abstract
Diagnostic devices for point-of-care (POC) urine analysis (urinalysis) based on microfluidic technology have been actively developing for several decades as an alternative to laboratory based biochemical assays. Urine proteins (albumin, immunoglobulins, uromodulin, haemoglobin etc.) are important biomarkers of various pathological conditions and should [...] Read more.
Diagnostic devices for point-of-care (POC) urine analysis (urinalysis) based on microfluidic technology have been actively developing for several decades as an alternative to laboratory based biochemical assays. Urine proteins (albumin, immunoglobulins, uromodulin, haemoglobin etc.) are important biomarkers of various pathological conditions and should be selectively detected by urinalysis sensors. The challenge is a determination of different oligomeric forms of the same protein, e.g., uromodulin, which have similar bio-chemical affinity but different physical properties. For the selective detection of different types of proteins, we propose to use a shear bulk acoustic resonator sensor with an additional electrode on the upper part of the bioliquid-filled channel for protein electric field manipulation. It causes modulation of the protein concentration over time in the near-surface region of the acoustic sensor, that allows to distinguish proteins based on their differences in diffusion coefficients (or sizes) and zeta-potentials. Moreover, in order to improve the sensitivity to density, we propose to use structured sensor interface. A numerical study of this approach for the detection of proteins was carried out using the example of albumin, immunoglobulin, and oligomeric forms of uromodulin in model urine solutions. In this contribution we prove the proposed concept with numerical studies for the detection of albumin, immunoglobulin, and oligomeric forms of uromodulin in urine models. Full article
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13 pages, 2757 KiB  
Article
Raman Spectroscopy-Based Quality Control of “Silicon-On-Insulator” Nanowire Chips for the Detection of Brain Cancer-Associated MicroRNA in Plasma
by Kristina A. Malsagova, Vladimir P. Popov, Igor N. Kupriyanov, Tatyana O. Pleshakova, Rafael A. Galiullin, Andrey F. Kozlov, Ivan D. Shumov, Dmitry I. Larionov, Fedor V. Tikhonenko, Svetlana I. Kapustina, Vadim S. Ziborov, Oleg F. Petrov, Olga A. Gadzhieva, Boris A. Bashiryan, Vadim N. Shimansky, Alexander I. Archakov and Yuri D. Ivanov
Sensors 2021, 21(4), 1333; https://doi.org/10.3390/s21041333 - 13 Feb 2021
Cited by 6 | Viewed by 2536
Abstract
Application of micro-Raman spectroscopy for the monitoring of quality of nanowire sensor chips fabrication has been demonstrated. Nanowire chips have been fabricated on the basis of «silicon-on-insulator» (SOI) structures (SOI-NW chips). The fabrication of SOI-NW chips was performed by optical litography with gas-phase [...] Read more.
Application of micro-Raman spectroscopy for the monitoring of quality of nanowire sensor chips fabrication has been demonstrated. Nanowire chips have been fabricated on the basis of «silicon-on-insulator» (SOI) structures (SOI-NW chips). The fabrication of SOI-NW chips was performed by optical litography with gas-phase etching. The so-fabricated SOI-NW chips are intended for highly sensitive detection of brain cancer biomarkers in humans. In our present study, two series of experiments have been conducted. In the first experimental series, detection of a synthetic DNA oligonucleotide (oDNA) analogue of brain cancer-associated microRNA miRNA-363 in purified buffer solution has been performed in order to demonstrate the high detection sensitivity. The second experimental series has been performed in order to reveal miRNA-363 itself in real human plasma samples. To provide detection biospecificity, the SOI-NW chip surface was modified by covalent immobilization of probe oligonucleotides (oDNA probes) complementary to the target biomolecules. Using the SOI-NW sensor chips proposed herein, the concentration detection limit of the target biomolecules at the level of 3.3 × 10−17 M has been demonstrated. Thus, the approach employing the SOI-NW chips proposed herein represents an attractive tool in biomedical practice, aimed at the early revelation of oncological diseases in humans. Full article
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2020

Jump to: 2022, 2021

13 pages, 1325 KiB  
Article
A Novel NIR-FRET Biosensor for Reporting PS/γ-Secretase Activity in Live Cells
by Mei CQ Houser, Steven S Hou, Florian Perrin, Yuliia Turchyna, Brian J Bacskai, Oksana Berezovska and Masato Maesako
Sensors 2020, 20(21), 5980; https://doi.org/10.3390/s20215980 - 22 Oct 2020
Cited by 6 | Viewed by 2390
Abstract
Presenilin (PS)/γ-secretase plays a pivotal role in essential cellular events via proteolytic processing of transmembrane proteins that include APP and Notch receptors. However, how PS/γ-secretase activity is spatiotemporally regulated by other molecular and cellular factors and how the changes in PS/γ-secretase activity influence [...] Read more.
Presenilin (PS)/γ-secretase plays a pivotal role in essential cellular events via proteolytic processing of transmembrane proteins that include APP and Notch receptors. However, how PS/γ-secretase activity is spatiotemporally regulated by other molecular and cellular factors and how the changes in PS/γ-secretase activity influence signaling pathways in live cells are poorly understood. These questions could be addressed by engineering a new tool that enables multiplexed imaging of PS/γ-secretase activity and additional cellular events in real-time. Here, we report the development of a near-infrared (NIR) FRET-based PS/γ-secretase biosensor, C99 720-670 probe, which incorporates an immediate PS/γ-secretase substrate APP C99 with miRFP670 and miRFP720 as the donor and acceptor fluorescent proteins, respectively. Extensive validation demonstrates that the C99 720-670 biosensor enables quantitative monitoring of endogenous PS/γ-secretase activity on a cell-by-cell basis in live cells (720/670 ratio: 2.47 ± 0.66 (vehicle) vs. 3.02 ± 1.17 (DAPT), ** p < 0.01). Importantly, the C99 720-670 and the previously developed APP C99 YPet-Turquoise-GL (C99 Y-T) biosensors simultaneously report PS/γ-secretase activity. This evidences the compatibility of the C99 720-670 biosensor with cyan (CFP)-yellow fluorescent protein (YFP)-based FRET biosensors for reporting other essential cellular events. Multiplexed imaging using the novel NIR biosensor C99 720-670 would open a new avenue to better understand the regulation and consequences of changes in PS/γ-secretase activity. Full article
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