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Biosensors
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Advances in Biosensors Based on Reflectometry
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Advances in Biosensors Based on Reflectometry

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

Deadline for manuscript submissions: closed (20 May 2024) | Viewed by 11411

Special Issue Editors

Dr. Günther Proll

E-Mail Website
Guest Editor
Institute of Physical and Theoretical Chemistry, Eberhard Karls Universität, Auf der Morgenstelle 18, 72076 Tübingen, Germany
Interests: optical biosensors; label-free high-throughput screening of biopharmaceuticals; process monitoring; immunoassays; biomolecular interactions; assay development for point-of-care testing (POCT) and environmental sensing; environmental analysis; effect directed analytics; bioanalytics; microarrays; infectious diseases; immunology; surface chemistry; microfluidics
Dr. Peter Fechner

E-Mail Website
Guest Editor
Institute of Physical and Theoretical Chemistry, Eberhard Karls Universität, Auf der Morgenstelle 18, 72076 Tübingen, Germany
Interests: biochemistry; biosensors; kinetics; effect directed analytics; molecular diagnostics; AI; optics; label-free screening

Special Issue Information

Dear Colleagues,

Today, direct optical biosensors have found their place in bioanalytics since they provide valuable data on kinetics and thermodynamics, do not require complicated sample pre-treatment and can be used for direct test formats. In the last 10-15 years, reflectometric measurement methods in particular, which are usually derived from ellipsometry, have gained in importance over refractometric transduction principles, although the boundaries between these areas sometimes seem to become blurred. Basically, however, reflectometry in biosensing is characterized by the typical feature that multiple reflections of electromagnetic radiation on at least one thin layer are used for signal generation. The driving force behind the many current developments is, among other things, applications that benefit, for example, from the ease of parallelization, the connection to common sample handling formats or, finally, the robustness towards temperature fluctuations in real-world operation. Against this background, this special issue of "Biosensors" will highlight the latest developments in reflectometric transduction and report on current applications such as the screening of biologics, biomolecular interaction analysis of receptors and ligands relevant to molecular medicine, as well as cell-based assays and diagnostics. All components of the biosensor, from the sensor surface to microfluidics and data analysis, are relevant, regardless in which area this technology is used.

Dr. Günther Proll
Dr. Peter Fechner
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

  • biosensor
  • reflectometry
  • label-free
  • kinetics
  • biomolecular interaction analysis
  • optical transduction
  • screening
  • biologics
  • cell-based assays

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Published Papers (6 papers)

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Research

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16 pages, 3834 KiB  
Article
A Device-on-Chip Solution for Real-Time Diffuse Correlation Spectroscopy Using FPGA
by Christopher H. Moore, Ulas Sunar and Wei Lin
Biosensors 2024, 14(8), 384; https://doi.org/10.3390/bios14080384 - 8 Aug 2024
Viewed by 807
Abstract
Diffuse correlation spectroscopy (DCS) is a non-invasive technology for the evaluation of blood perfusion in deep tissue. However, it requires high computational resources for data analysis, which poses challenges in its implementation for real-time applications. To address the unmet need, we developed a [...] Read more.
Diffuse correlation spectroscopy (DCS) is a non-invasive technology for the evaluation of blood perfusion in deep tissue. However, it requires high computational resources for data analysis, which poses challenges in its implementation for real-time applications. To address the unmet need, we developed a novel device-on-chip solution that fully integrates all the necessary computational components needed for DCS. It takes the output of a photon detector and determines the blood flow index (BFI). It is implemented on a field-programmable gate array (FPGA) chip including a multi-tau correlator for the calculation of the temporal light intensity autocorrelation function and a DCS analyzer to perform the curve fitting operation that derives the BFI at a rate of 6000 BFIs/s. The FPGA DCS system was evaluated against a lab-standard DCS system for both phantom and cuff ischemia studies. The results indicate that the autocorrelation of the light correlation and BFI from both the FPGA DCS and the reference DCS matched well. Furthermore, the FPGA DCS system was able to achieve a measurement rate of 50 Hz and resolve pulsatile blood flow. This can significantly lower the cost and footprint of the computational components of DCS and pave the way for portable, real-time DCS systems. Full article
(This article belongs to the Special Issue Advances in Biosensors Based on Reflectometry)
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12 pages, 3229 KiB  
Article
Protein Identification and Quantification Using Porous Silicon Arrays, Optical Measurements, and Machine Learning
by Simon J. Ward, Tengfei Cao, Xiang Zhou, Catie Chang and Sharon M. Weiss
Biosensors 2023, 13(9), 879; https://doi.org/10.3390/bios13090879 - 9 Sep 2023
Cited by 1 | Viewed by 1866
Abstract
We report a versatile platform based on an array of porous silicon (PSi) thin films that can identify analytes based on their physical and chemical properties without the use of specific capture agents. The ability of this system to reproducibly classify, quantify, and [...] Read more.
We report a versatile platform based on an array of porous silicon (PSi) thin films that can identify analytes based on their physical and chemical properties without the use of specific capture agents. The ability of this system to reproducibly classify, quantify, and discriminate three proteins separately is demonstrated by probing the reflectance of PSi array elements with a unique combination of pore size and buffer pH, and by analyzing the optical signals using machine learning. Protein identification and discrimination are reported over a concentration range of two orders of magnitude. This work represents a significant first step towards a low-cost, simple, versatile, and robust sensor platform that is able to detect biomolecules without the added expense and limitations of using capture agents. Full article
(This article belongs to the Special Issue Advances in Biosensors Based on Reflectometry)
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16 pages, 2060 KiB  
Article
Simultaneous Detection of SARS-CoV-2 Nucleoprotein and Receptor Binding Domain by a Multi-Area Reflectance Spectroscopy Sensor
by Dimitra Tsounidi, Michailia Angelopoulou, Panagiota Petrou, Ioannis Raptis and Sotirios Kakabakos
Biosensors 2023, 13(9), 865; https://doi.org/10.3390/bios13090865 - 1 Sep 2023
Viewed by 1286
Abstract
The COVID-19 pandemic has emphasized the urgent need for point-of-care methods suitable for the rapid and reliable diagnosis of viral infections. To address this demand, we report the rapid, label-free simultaneous determination of two SARS-CoV-2 proteins, namely, the nucleoprotein and the receptor binding [...] Read more.
The COVID-19 pandemic has emphasized the urgent need for point-of-care methods suitable for the rapid and reliable diagnosis of viral infections. To address this demand, we report the rapid, label-free simultaneous determination of two SARS-CoV-2 proteins, namely, the nucleoprotein and the receptor binding domain peptide of S1 protein, by implementing a bioanalytical device based on Multi Area Reflectance Spectroscopy. Simultaneous detection of these two proteins is achieved by using silicon chips with adjacent areas of different silicon dioxide thickness on top, each of which is modified with an antibody specific to either the nucleoprotein or the receptor binding domain of SARS-CoV-2. Both areas were illuminated by a single probe that also collected the reflected light, directing it to a spectrometer. The online conversion of the combined reflection spectra from the two silicon dioxide areas into the respective adlayer thickness enabled real-time monitoring of immunoreactions taking place on the two areas. Several antibodies have been tested to define the pair, providing the higher specific signal following a non-competitive immunoassay format. Biotinylated secondary antibodies and streptavidin were used to enhance the specific signal. Both proteins were detected in less than 12 min, with detection limits of 1.0 ng/mL. The assays demonstrated high repeatability with intra- and inter-assay coefficients of variation lower than 10%. Moreover, the recovery of both proteins from spiked samples prepared in extraction buffer from a commercial self-test kit for SARS-CoV-2 collection from nasopharyngeal swabs ranged from 90.0 to 110%. The short assay duration in combination with the excellent analytical performance and the compact instrument size render the proposed device and assay suitable for point-of-care applications. Full article
(This article belongs to the Special Issue Advances in Biosensors Based on Reflectometry)
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13 pages, 3760 KiB  
Article
(R)evolution of the Standard Addition Procedure for Immunoassays
by Monika Conrad, Peter Fechner, Günther Proll and Günter Gauglitz
Biosensors 2023, 13(9), 849; https://doi.org/10.3390/bios13090849 - 25 Aug 2023
Viewed by 1714
Abstract
A new method to transfer the standard addition procedure for concentration determination to immunoassays with non-linear calibration curves was developed. The new method was successfully applied to simulated data and benchmarked against a state-of-the-art algorithm, showing a significantly improved performance with improvement factors [...] Read more.
A new method to transfer the standard addition procedure for concentration determination to immunoassays with non-linear calibration curves was developed. The new method was successfully applied to simulated data and benchmarked against a state-of-the-art algorithm, showing a significantly improved performance with improvement factors between 2 and 192. The logit function was used to transform the immunoassay signal response of test samples spiked with known analyte concentrations. The relationship between logit(signal) and log-transformed estimated total analyte concentration is linear if the estimated total analyte concentration is correct. Finally, the new method was validated experimentally using different assays in varying, relevant complex matrices, such as serum, saliva, and milk. Different concentrations of testosterone and amitriptyline between 0.05 and 3.0 µg L−1 were quantified using a binding inhibition assay in combination with reflectometric interference spectroscopy (RIfS) as the transduction principle. The sample concentration was calculated using a numerical method. Samples could be quantified with recoveries between 70 and 118%. The standard addition method accounts for individual matrix interference on the immunoassay by spiking the test sample itself. Although the experiments were carried out using RIfS, the method can be applied to any immunoassay that meets the analytical requirements. Full article
(This article belongs to the Special Issue Advances in Biosensors Based on Reflectometry)
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Review

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11 pages, 2584 KiB  
Review
Two Decades of Arrayed Imaging Reflectometry for Sensitive, High-Throughput Biosensing
by Gabrielle Kosoy and Benjamin L. Miller
Biosensors 2023, 13(9), 870; https://doi.org/10.3390/bios13090870 - 5 Sep 2023
Cited by 3 | Viewed by 3488
Abstract
Arrayed imaging reflectometry (AIR), first introduced in 2004, is a thin-film interference sensor technique that optimizes optical properties (angle of incidence, polarization, substrate refractive index, and thickness) to create a condition of total destructive interference at the surface of a silicon substrate. The [...] Read more.
Arrayed imaging reflectometry (AIR), first introduced in 2004, is a thin-film interference sensor technique that optimizes optical properties (angle of incidence, polarization, substrate refractive index, and thickness) to create a condition of total destructive interference at the surface of a silicon substrate. The advantages of AIR are its sensitivity, dynamic range, multiplex capability, and high-throughput compatibility. AIR has been used for the detection of antibodies against coronaviruses, influenza viruses, Staphylococcus aureus, and human autoantigens. It has also shown utility in detection of cytokines, with sensitivity comparable to bead-based and ELISA assays. Not limited to antibodies or antigens, mixed aptamer and protein arrays as well as glycan arrays have been employed in AIR for differentiating influenza strains. Mixed arrays using direct and competitive inhibition assays have enabled simultaneous measurement of cytokines and small molecules. Finally, AIR has also been used to measure affinity constants, kinetic and at equilibrium. In this review, we give an overview of AIR biosensing technologies and present the latest AIR advances. Full article
(This article belongs to the Special Issue Advances in Biosensors Based on Reflectometry)
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21 pages, 4271 KiB  
Review
From Self-Assembly of Colloidal Crystals toward Ordered Porous Layer Interferometry
by Yi-Zhen Wan and Weiping Qian
Biosensors 2023, 13(7), 730; https://doi.org/10.3390/bios13070730 - 13 Jul 2023
Cited by 6 | Viewed by 1631
Abstract
Interferometry-based, reflectometric, label-free biosensors have made significant progress in the analysis of molecular interactions after years of development. The design of interference substrates is a key research topic for these biosensors, and many studies have focused on porous films prepared by top-down methods [...] Read more.
Interferometry-based, reflectometric, label-free biosensors have made significant progress in the analysis of molecular interactions after years of development. The design of interference substrates is a key research topic for these biosensors, and many studies have focused on porous films prepared by top-down methods such as porous silicon and anodic aluminum oxide. Lately, more research has been conducted on ordered porous layer interferometry (OPLI), which uses ordered porous colloidal crystal films as interference substrates. These films are made using self-assembly techniques, which is the bottom-up approach. They also offer several advantages for biosensing applications, such as budget cost, adjustable porosity, and high structural consistency. This review will briefly explain the fundamental components of self-assembled materials and thoroughly discuss various self-assembly techniques in depth. We will also summarize the latest studies that used the OPLI technique for label-free biosensing applications and divide them into several aspects for further discussion. Then, we will comprehensively evaluate the strengths and weaknesses of self-assembly techniques and discuss possible future research directions. Finally, we will outlook the upcoming challenges and opportunities for label-free biosensing using the OPLI technique. Full article
(This article belongs to the Special Issue Advances in Biosensors Based on Reflectometry)
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