Bioprocess Monitoring, Measurement, and Control by Biosensor-Based Technologies

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

Deadline for manuscript submissions: closed (28 February 2022) | Viewed by 24438

Special Issue Editors


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Guest Editor
School of Physical Sciences, The University of Adelaide, Adelaide, SA 5005, Australia
Interests: online monitoring of bioprocesses including fermentation, cell culture, and biofuel production using optical spectral analysis technologies; micro- and nano-structured fibers based on silica and soft glasses; fast detection of raw materials and agriculture food; fiber-based surface plasmon resonance protein sensors; petrol/oil sensing; gas sensing; detection of environmental pollutants and food safety; fiber-based single-photon sources; fiber magnetometry based on nitrogen-vacancy centers; fiber/cavity-based biosensing; surface-enhanced Raman scattering and field enhanced fluorescence

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Guest Editor
Nanobiosensorics Laboratory, Institute for Technical Physics and Materials Science, Centre for Energy Research, Hungarian Academy of Sciences, H-1120 Budapest, Hungary
Interests: label-free biosensors; optics; waveguides; cell-based sensors; tissue on a chip; cell adhesion; protein adsorption; single cell; sensor coatings; kinetics

Special Issue Information

Dear Colleagues,

Online analysis of bioprocesses is of increasing interest because it helps to reduce the time delay for offline sample preparation and following analyses via conventional methods. Continuous monitoring of reaction components is a prerequisite for the direct control of biotransformations. An ideal analytical system should ensure that each individual process can be monitored separately without interfering with the process itself and with minimized risk of contamination. Well established liquid chromatography and mass spectrometer are being used to for online analysis. The optical spectral analysis technologies are very attractive to perform this task because of the advantages of being non-invasive, non-destructive, and capable of taking measurements both offline and inline, and enabling quantitative analysis of multiple components in real-time. This Special Issue encompasses a broad range of optical spectral sensors including UV/NIR/MIR spectroscopy, Raman spectroscopy, fluorescence spectroscopy, optical waveguide sensing and surface plasmon resonance, and their at-line and online applications. Novel optics or fiber/waveguide probes with improved collection efficiency are welcome. Further topics that will be covered include any novel methods suitable for online bioprocess analysis with minimum interference. The application scenarios include but are not limited to the production of pharmaceuticals, chemicals, fuels, and food.

Dr. Yinlan Ruan
Dr. Robert Horvath
Guest Editors

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Keywords

  • online monitoring
  • bioprocessing
  • ultraviolet spectroscopy
  • near-infrared spectroscopy
  • Mid-IR infrared spectroscopy
  • raman spectroscopy
  • surface plasmon resonance
  • optical waveguide resonances
  • data analysis
  • chemometrics
  • machine learning

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Published Papers (7 papers)

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Research

13 pages, 1856 KiB  
Article
Non-Destructive Genotyping of Cultivars and Strains of Sesame through NIR Spectroscopy and Chemometrics
by Francisco dos Santos Panero, Oscar Smiderle, João S. Panero, Fernando S. D. V. Faria, Pedro dos S. Panero and Anselmo F. R. Rodriguez
Biosensors 2022, 12(2), 69; https://doi.org/10.3390/bios12020069 - 26 Jan 2022
Cited by 8 | Viewed by 2827
Abstract
The differentiation of cultivars is carried out by means of morphological descriptors, in addition to molecular markers. In this work, near-infrared spectroscopy (NIR) and chemometric techniques were used to develop classification models for two different commercial sesame cultivars (Sesamum indicum) and [...] Read more.
The differentiation of cultivars is carried out by means of morphological descriptors, in addition to molecular markers. In this work, near-infrared spectroscopy (NIR) and chemometric techniques were used to develop classification models for two different commercial sesame cultivars (Sesamum indicum) and 3 different strains. The diffuse reflectance spectra were recorded in the region of 700 to 2500 nm. Based on the application of chemometric techniques: principal component analysis—PCA, hierarchical cluster analysis—HCA, k-nearest neighbor—KNN and the flexible independent modeling of class analogy—SIMCA, from the infrared spectra in the near region, it was possible to perform the genotyping of two sesame cultivars (BRS Seda and BRS Anahí), and to classify these cultivars with 3 different sesame strains, obtaining 100% accurate results. Due to the good results obtained with the implemented models, the potential of the methods for a possible realization of forensic, fast and non-destructive authentication, in intact sesame seeds was evident. Full article
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13 pages, 18007 KiB  
Article
On-Line Monitoring of Biofilm Accumulation on Graphite-Polypropylene Electrode Material Using a Heat Transfer Sensor
by Andreas Netsch, Harald Horn and Michael Wagner
Biosensors 2022, 12(1), 18; https://doi.org/10.3390/bios12010018 - 30 Dec 2021
Cited by 5 | Viewed by 2611
Abstract
Biofilms growing on electrodes are the heart piece of bioelectrochemical systems (BES). Moreover, the biofilm morphology is key for the efficient performance of BES and must be monitored and controlled for a stable operation. For the industrial use of BES (i.e., microbial fuel [...] Read more.
Biofilms growing on electrodes are the heart piece of bioelectrochemical systems (BES). Moreover, the biofilm morphology is key for the efficient performance of BES and must be monitored and controlled for a stable operation. For the industrial use of BES (i.e., microbial fuel cells for energy production), monitoring of the biofilm accumulation directly on the electrodes during operation is desirable. In this study a commercially available on-line heat transfer biofilm sensor is applied to a graphite-polypropylene (C-PP) pipe and compared to its standard version where the sensor is applied to a stainless-steel pipe. The aim was to investigate the transferability of the sensor to a carbonaceous material (C-PP), that are preferably used as electrode materials for bioelectrochemical systems, thereby enabling biofilm monitoring directly on the electrode surface. The sensor signal was correlated to the gravimetrically determined biofilm thickness in order to identify the sensitivity of the sensor for the detection and quantification of biofilm on both materials. Results confirmed the transferability of the sensor to the C-PP material, despite the sensor sensitivity being decreased by a factor of approx. 5 compared to the default biofilm sensor applied to a stainless-steel pipe. Full article
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12 pages, 854 KiB  
Article
SERSNet: Surface-Enhanced Raman Spectroscopy Based Biomolecule Detection Using Deep Neural Network
by Seongyong Park, Jaeseok Lee, Shujaat Khan, Abdul Wahab and Minseok Kim
Biosensors 2021, 11(12), 490; https://doi.org/10.3390/bios11120490 - 30 Nov 2021
Cited by 6 | Viewed by 4296
Abstract
Surface-Enhanced Raman Spectroscopy (SERS)-based biomolecule detection has been a challenge due to large variations in signal intensity, spectral profile, and nonlinearity. Recent advances in machine learning offer great opportunities to address these issues. However, well-documented procedures for model development and evaluation, as well [...] Read more.
Surface-Enhanced Raman Spectroscopy (SERS)-based biomolecule detection has been a challenge due to large variations in signal intensity, spectral profile, and nonlinearity. Recent advances in machine learning offer great opportunities to address these issues. However, well-documented procedures for model development and evaluation, as well as benchmark datasets, are lacking. Towards this end, we provide the SERS spectral benchmark dataset of Rhodamine 6G (R6G) for a molecule detection task and evaluate the classification performance of several machine learning models. We also perform a comparative study to find the best combination between the preprocessing methods and the machine learning models. Our best model, coined as the SERSNet, robustly identifies R6G molecule with excellent independent test performance. In particular, SERSNet shows 95.9% balanced accuracy for the cross-batch testing task. Full article
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13 pages, 3395 KiB  
Article
Microfluidic Raman Sensing Using a Single Ring Negative Curvature Hollow Core Fiber
by Xinyu Wang, Shuguang Li, Shoufei Gao, Yingying Wang, Pu Wang, Heike Ebendorff-Heidepriem and Yinlan Ruan
Biosensors 2021, 11(11), 430; https://doi.org/10.3390/bios11110430 - 30 Oct 2021
Cited by 3 | Viewed by 2406
Abstract
A compact microfluidic Raman detection system based on a single-ring negative-curvature hollow-core fiber is presented. The system can be used for in-line qualitative and quantitative analysis of biochemicals. Both efficient light coupling and continuous liquid injection into the hollow-core fiber were achieved by [...] Read more.
A compact microfluidic Raman detection system based on a single-ring negative-curvature hollow-core fiber is presented. The system can be used for in-line qualitative and quantitative analysis of biochemicals. Both efficient light coupling and continuous liquid injection into the hollow-core fiber were achieved by creating a small gap between a solid-core fiber and the hollow-core fiber, which were fixed within a low-cost ceramic ferrule. A coupling efficiency of over 50% from free-space excitation laser to the hollow core fiber was obtained through a 350 μm-long solid-core fiber. For proof-of-concept demonstration of bioprocessing monitoring, a series of ethanol and glucose aqueous solutions at different concentrations were used. The limit of detection achieved for the ethanol solutions with our system was ~0.04 vol.% (0.32 g/L). Such an all-fiber microfluidic device is robust, provides Raman measurements with high repeatability and reusability, and is particularly suitable for the in-line monitoring of bioprocesses. Full article
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13 pages, 1985 KiB  
Article
Fibre-Optic Surface Plasmon Resonance Biosensor for Monoclonal Antibody Titer Quantification
by Thai Thao Ly, Yinlan Ruan, Bobo Du, Peipei Jia and Hu Zhang
Biosensors 2021, 11(10), 383; https://doi.org/10.3390/bios11100383 - 10 Oct 2021
Cited by 7 | Viewed by 3602
Abstract
An extraordinary optical transmission fibre-optic surface plasmon resonance biosensing platform was engineered to improve its portability and sensitivity, and was applied to monitor the concentrations of monoclonal antibodies (Mabs). By refining the fabricating procedure and changing the material of the flow cell and [...] Read more.
An extraordinary optical transmission fibre-optic surface plasmon resonance biosensing platform was engineered to improve its portability and sensitivity, and was applied to monitor the concentrations of monoclonal antibodies (Mabs). By refining the fabricating procedure and changing the material of the flow cell and the components of the optical fibre, the biosensor is portable and robust to external interference. After the implementation of an effective template cleaning procedure and precise control during the fabrication process, a consistent sensitivity of 509 ± 5 nm per refractive index unit (nm/RIU) was achieved. The biosensor can detect the Mab with a limit of detection (LOD) of 0.44 µg/mL. The results show that the biosensor is a potential tool for the rapid quantification of Mab titers. The biosensor can be regenerated at least 10 times with 10 mM glycine (pH = 2.5), and consistent signal changes were obtained after regeneration. Moreover, the employment of a spacer arm SM(PEG)2, used for immobilising protein A onto the gold film, was demonstrated to be unable to improve the detecting sensitivity; thus, a simple procedure without the spacer arm could be used to prepare the protein A-based biosensor. Our results demonstrate that the fibre-optic surface plasmon resonance biosensor is competent for the real-time and on-line monitoring of antibody titers in the future as a process analytical technologies (PATs) tool for bioprocess developments and the manufacture of therapeutic antibodies. Full article
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11 pages, 3782 KiB  
Article
Dissociation Constant of Integrin-RGD Binding in Live Cells from Automated Micropipette and Label-Free Optical Data
by Tamás Gerecsei, Péter Chrenkó, Nicolett Kanyo, Beatrix Péter, Attila Bonyár, Inna Székács, Balint Szabo and Robert Horvath
Biosensors 2021, 11(2), 32; https://doi.org/10.3390/bios11020032 - 24 Jan 2021
Cited by 9 | Viewed by 3880
Abstract
The binding of integrin proteins to peptide sequences such as arginine-glycine-aspartic acid (RGD) is a crucial step in the adhesion process of mammalian cells. While these bonds can be examined between purified proteins and their ligands, live-cell assays are better suited to gain [...] Read more.
The binding of integrin proteins to peptide sequences such as arginine-glycine-aspartic acid (RGD) is a crucial step in the adhesion process of mammalian cells. While these bonds can be examined between purified proteins and their ligands, live-cell assays are better suited to gain biologically relevant information. Here we apply a computer-controlled micropipette (CCMP) to measure the dissociation constant (Kd) of integrin-RGD-binding. Surface coatings with varying RGD densities were prepared, and the detachment of single cells from these surfaces was measured by applying a local flow inducing hydrodynamic lifting force on the targeted cells in discrete steps. The average behavior of the populations was then fit according to the chemical law of mass action. To verify the resulting value of Kd2d = (4503 ± 1673) 1/µm2, a resonant waveguide grating based biosensor was used, characterizing and fitting the adhesion kinetics of the cell populations. Both methods yielded a Kd within the same range. Furthermore, an analysis of subpopulations was presented, confirming the ability of CCMP to characterize cell adhesion both on single cell and whole population levels. The introduced methodologies offer convenient and automated routes to quantify the adhesivity of living cells before their further processing. Full article
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17 pages, 16368 KiB  
Article
A Self-Referenced Diffraction-Based Optical Leaky Waveguide Biosensor Using Photofunctionalised Hydrogels
by Anil K. Pal, Nicholas J. Goddard, Hazel J. Dixon and Ruchi Gupta
Biosensors 2020, 10(10), 134; https://doi.org/10.3390/bios10100134 - 24 Sep 2020
Cited by 10 | Viewed by 3581
Abstract
We report a novel self-referenced diffraction-based leaky waveguide (LW) comprising a thin (~2 µm) film of a photofunctionalisable hydrogel created by covalent attachment of a biotinylated photocleavable linker to chitosan. Streptavidin attached to the chitosan via the photocleavable linker was selectively removed by [...] Read more.
We report a novel self-referenced diffraction-based leaky waveguide (LW) comprising a thin (~2 µm) film of a photofunctionalisable hydrogel created by covalent attachment of a biotinylated photocleavable linker to chitosan. Streptavidin attached to the chitosan via the photocleavable linker was selectively removed by shining 365 nm light through a photomask to create an array of strips with high and low loading of the protein, which served as sensor and reference regions respectively. The differential measurements between sensor and reference regions were used for measuring analytes (i.e., biotin protein A and IgG) while reducing environmental and non-specific effects. These include changes in temperature and sample composition caused by non-adsorbing and adsorbing species, leading to reduction in effects by ~98%, ~99%, and ~97% respectively compared to the absolute measurements. The novelty of this work lies in combining photofunctionalisable hydrogels with diffraction-based LWs for referencing. This is needed to realise the full potential of label-free optical biosensors to measure analyte concentrations in real samples that are complex mixtures, and to allow for sample analysis outside of laboratories where drifts and fluctuations in temperature are observed. Full article
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