Molecularly Imprinted Polymers for the Determination of Cancer Biomarkers.

Biomarkers can provide critical information about cancer and many other diseases; therefore, developing analytical systems for recognising biomarkers is an essential direction in bioanalytical chemistry. Recently molecularly imprinted polymers (MIPs) have been applied in analytical systems to determine biomarkers. This article aims to an overview of MIPs used for the detection of cancer biomarkers, namely: prostate cancer (PSA), breast cancer (CA15-3, HER-2), epithelial ovarian cancer (CA-125), hepatocellular carcinoma (AFP), and small molecule cancer biomarkers (5-HIAA and neopterin). These cancer biomarkers may be found in tumours, blood, urine, faeces, or other body fluids or tissues. The determination of low concentrations of biomarkers in these complex matrices is technically challenging. The overviewed studies used MIP-based biosensors to assess natural or artificial samples such as blood, serum, plasma, or urine. Molecular imprinting technology and MIP-based sensor creation principles are outlined. Analytical signal determination methods and the nature and chemical structure of the imprinted polymers are discussed. Based on the reviewed biosensors, the results are compared, and the most suitable materials for each biomarker are discussed.

Electrochemically Deposited Molecularly Imprinted Polymer-Based Sensors.

This review is dedicated to the development of molecularly imprinted polymers (MIPs) and the application of MIPs in sensor design. MIP-based biological recognition parts can replace receptors or antibodies, which are rather expensive. Conducting polymers show unique properties that are applicable in sensor design. Therefore, MIP-based conducting polymers, including polypyrrole, polythiophene, poly(3,4-ethylenedioxythiophene), polyaniline and ortho-phenylenediamine are frequently applied in sensor design. Some other materials that can be molecularly imprinted are also overviewed in this review. Among many imprintable materials conducting polymer, polypyrrole is one of the most suitable for molecular imprinting of various targets ranging from small organics up to rather large proteins. Some attention in this review is dedicated to overview methods applied to design MIP-based sensing structures. Some attention is dedicated to the physicochemical methods applied for the transduction of analytical signals. Expected new trends and horizons in the application of MIP-based structures are also discussed.

From Microorganism-Based Amperometric Biosensors towards Microbial Fuel Cells.

This review focuses on the overview of microbial amperometric biosensors and microbial biofuel cells (MFC) and shows how very similar principles are applied for the design of both types of these bioelectronics-based devices. Most microorganism-based amperometric biosensors show poor specificity, but this drawback can be exploited in the design of microbial biofuel cells because this enables them to consume wider range of chemical fuels. The efficiency of the charge transfer is among the most challenging and critical issues during the development of any kind of biofuel cell. In most cases, particular redox mediators and nanomaterials are applied for the facilitation of charge transfer from applied biomaterials towards biofuel cell electrodes. Some improvements in charge transfer efficiency can be achieved by the application of conducting polymers (CPs), which can be used for the immobilization of enzymes and in some particular cases even for the facilitation of charge transfer. In this review, charge transfer pathways and mechanisms, which are suitable for the design of biosensors and in biofuel cells, are discussed. Modification methods of the cell-wall/membrane by conducting polymers in order to enhance charge transfer efficiency of microorganisms, which can be potentially applied in the design of microbial biofuel cells, are outlined. The biocompatibility-related aspects of conducting polymers with microorganisms are summarized.

Insights in the Application of Stoichiometric and Non-Stoichiometric Titanium Oxides for the Design of Sensors for the Determination of Gases and VOCs (TiO2-x and TinO2n-1 vs. TiO2).

In this review article, attention is paid towards the formation of various nanostructured stoichiometric titanium dioxide (TiO2), non-stoichiometric titanium oxide (TiO2-x) and Magnéli phase (TinO2n-1)-based layers, which are suitable for the application in gas and volatile organic compound (VOC) sensors. Some aspects related to variation of sensitivity and selectivity of titanium oxide-based sensors are critically overviewed and discussed. The most promising titanium oxide-based hetero- and nano-structures are outlined. Recent research and many recently available reviews on TiO2-based sensors and some TiO2 synthesis methods are discussed. Some promising directions for the development of TiO2-based sensors, especially those that are capable to operate at relatively low temperatures, are outlined. The applicability of non-stoichiometric titanium oxides in the development of gas and VOC sensors is foreseen and transitions between various titanium oxide states are discussed. The presence of non-stoichiometric titanium oxide and Magnéli phase (TinO2n-1)-based layers in 'self-heating' sensors is predicted, and the advantages and limitations of 'self-heating' gas and VOC sensors, based on TiO2 and TiO2-x/TiO2 heterostructures, are discussed.

Progress and Insights in the Application of MXenes as New 2D Nano-Materials Suitable for Biosensors and Biofuel Cell Design.

Recent progress in the application of new 2D-materials-MXenes-in the design of biosensors, biofuel cells and bioelectronics is overviewed and some advances in this area are foreseen. Recent developments in the formation of a relatively new class of 2D metallically conducting MXenes opens a new avenue for the design of conducting composites with metallic conductivity and advanced sensing properties. Advantageous properties of MXenes suitable for biosensing applications are discussed. Frontiers and new insights in the area of application of MXenes in sensorics, biosensorics and in the design of some wearable electronic devices are outlined. Some disadvantages and challenges in the application of MXene based structures are critically discussed.

TiO2-x/TiO2-Structure Based 'Self-Heated' Sensor for the Determination of Some Reducing Gases.

In this research we report the gas-sensing properties of TiO2-x/TiO2-based hetero-structure, which was 'self-heated' by current that at constant potential passed through the structure. Amperometric measurements were applied for the evaluation of sensor response towards ethanol, methanol, n-propanol and acetone gases/vapours. The sensitivity towards these gases was based on electrical resistance changes, which were determined by amperometric measurements of current at fixed voltage applied between Pt-based contacts/electrodes deposited on the TiO2-x/TiO2-based layer. X-ray diffraction (XRD) analysis revealed the formation of TiO2-x/TiO2-based hetero-structure, which is mainly based on Ti3O5/TiO2 formed during the hydro-thermal oxidation-based sensing-layer preparation process. Additionally, photoluminescence and time-resolved photoluminescence decay kinetics-based signals of this sensing structure revealed the presence of TiO2 mainly in the anatase phase in the TiO2-x/TiO2-based hetero-structure, which was formed at 400 °C annealing temperature. The evaluation of TiO2-x/TiO2-based gas-sensing layer was performed at several different temperatures (25 °C, 72 °C, 150 °C, 180 °C) and at these temperatures different sensitivity to the aforementioned gaseous materials was determined.

Molecular imprinting technology for biomedical applications.

Molecularly imprinted polymers (MIPs), a type of biomimetic material, have attracted considerable interest owing to their cost-effectiveness, good physiochemical stability, favourable specificity and selectivity for target analytes, and widely used for various biological applications. It was demonstrated that MIPs with significant selectivity towards protein-based targets could be applied in medicine, diagnostics, proteomics, environmental analysis, sensors, various in vivo and/or in vitro applications, drug delivery systems, etc. This review provides an overview of MIPs dedicated to biomedical applications and insights into perspectives on the application of MIPs in newly emerging areas of biotechnology. Many different protocols applied for the synthesis of MIPs are overviewed in this review. The templates used for molecular imprinting vary from the minor glycosylated glycan-based structures, amino acids, and proteins to whole bacteria, which are also overviewed in this review. Economic, environmental, rapid preparation, stability, and reproducibility have been highlighted as significant advantages of MIPs. Particularly, some specialized MIPs, in addition to molecular recognition properties, can have high catalytic activity, which in some cases could be compared with other bio-catalytic systems. Therefore, such MIPs belong to the class of so-called 'artificial enzymes'. The discussion provided in this manuscript furnishes a comparative analysis of different approaches developed, underlining their relative advantages and disadvantages highlighting trends and possible future directions of MIP technology.

MXene-Based Chemo-Sensors and Other Sensing Devices.

MXenes have received worldwide attention across various scientific and technological fields since the first report of the synthesis of Ti3C2 nanostructures in 2011. The unique characteristics of MXenes, such as superior mechanical strength and flexibility, liquid-phase processability, tunable surface functionality, high electrical conductivity, and the ability to customize their properties, have led to the widespread development and exploration of their applications in energy storage, electronics, biomedicine, catalysis, and environmental technologies. The significant growth in publications related to MXenes over the past decade highlights the extensive research interest in this material. One area that has a great potential for improvement through the integration of MXenes is sensor design. Strain sensors, temperature sensors, pressure sensors, biosensors (both optical and electrochemical), gas sensors, and environmental pollution sensors targeted at volatile organic compounds (VOCs) could all gain numerous improvements from the inclusion of MXenes. This report delves into the current research landscape, exploring the advancements in MXene-based chemo-sensor technologies and examining potential future applications across diverse sensor types.

Monitoring Ti3C2Tx MXene Degradation Pathways Using Raman Spectroscopy.

Extending applications of Ti3C2Tx MXene in nanocomposites and across fields of electronics, energy storage, energy conversion, and sensor technologies necessitates simple and efficient analytical methods. Raman spectroscopy is a critical tool for assessing MXene composites; however, high laser powers and temperatures can lead to the materials' deterioration during the analysis. Therefore, an in-depth understanding of MXene photothermal degradation and changes in its oxidation state is required, but no systematic studies have been reported. The primary aim of this study was to investigate the degradation of the MXene lattice through Raman spectroscopic analysis. Distinct spectral markers were related to structural alterations within the Ti3C2Tx material after subjecting it to thermal- and laser-induced degradation. During the degradation processes, spectral markers were revealed for several specific steps: a decrease in the number of interlayer water molecules, a decrease in the number of -OH groups, formation of C-C bonds, oxidation of the lattice, and formation of TiO2 nanoparticles (first anatase, followed by rutile). By tracking of position shifts and intensity changes for Ti3C2Tx, the spectral markers that signify the initiation of each step were found. This spectroscopic approach enhances our understanding of the degradation pathways of MXene, and facilitating enhanced and dependable integration of these materials into devices for diverse applications, from energy storage to sensors.

Electrochemical real-time sensor for the detection of Pb(II) ions based on Ti3C2Tx MXene.

Lead ions are especially harmful to human health, causing significant developmental and behavioral abnormalities even at small concentrations. In real-life samples, lead ions are present in mixtures with other metal ions, creating a challenge to detect it selectively at low quantities. To address these challenges, we prepared an electrochemical sensor based on delaminated Ti3C2Tx MXene, which can selectively detect low concentrations of Pb2+ in a solution containing other common metal ions. Cyclic voltammetry was applied as an electrochemical detection method. The proposed reaction mechanism involves a reversible transition between Pb2+ ions and PbO at the MXene-based layer. The sensitivity of the sensor towards Pb2+ ions and a limit of detection were determined. The sensor, as prepared, had a linear response range within 0.15-1.0 µM, with a sensitivity of 26.7 µA/µM and LOD value of 48.7 nM, which meets the requirements set by the World Health Organization.

Photoluminescence-based biosensor for the detection of antibodies against SARS-CoV-2 virus proteins by ZnO tetrapod structure integrated within microfluidic system.

This paper reports on development of an optical biosensor for the detection of antibodies against SARS-CoV-2 virus proteins in blood serum. ZnO nanotetrapods with high surface area and stable room temperature photoluminescence (PL) were selected as transducers. Structure and optical properties of the ZnO tetrapods have been studied by XRD, SEM and Raman spectroscopy. Crystallinity, dimensions and emission peaks of the ZnO tetrapods were determined. The ZnO tetrapods were fixed on glass chip. Silanization of ZnO tetrapods surface resulted in forming of functional surface groups suitable for the immobilization of bioselective layer. Two types of recombinant proteins (rS and rN) have been used to form bioselective layer on the surface of the ZnO tetrapods. Flow through microfluidic system, integrated with optical system, has been used for the determination of antibodies against SARS-CoV-2 virus proteins present in blood samples. The SARS-CoV-2 probes, prepared in PBS solution, have been injected into the measurement chamber with a constant pumping speed. Steady-state photoluminescence spectra and photoluminescence kinetics have been studied before and after injection of the probes. The biosensor signal has been tested to anti-SARS-CoV-2 antibodies in the range of 0.001 nM-1 nM. Control measurements have been performed with blood serum of healthy person. ZnO-SARS-CoV-2-rS and ZnO-SARS-CoV-2-rN biosensors showed high stability and sensitivity to anti-SARS-CoV-2 antibodies in the range of 0.025-0.5 nM (LOD 0.01 nM) and 0.3-1 nM (LOD 0.3 nM), respectively. Gibbs free energy of interaction between ZnO/SARS-CoV-2-rS and ZnO/SARS-CoV-2-rN bioselective layers with anti-SARS-CoV-2 antibodies showed -35.5 and -21.4 kJ/mol, respectively. Average detection time of biosensor integrated within microfluidic system was 15-20 min. The detection time and pumping speed (50 µL/min) were optimized to make detection faster. The developed system and ZnO-SARS-CoV-2-rS nanostructures have good potential for detection of anti-SARS-CoV-2 antibodies from patient's probes.

Molecularly Imprinted Polymer-Based Electrochemical Sensors for the Diagnosis of Infectious Diseases.

The appearance of biological molecules, so-called biomarkers in body fluids at abnormal concentrations, is considered a good tool for detecting disease. Biomarkers are usually looked for in the most common body fluids, such as blood, nasopharyngeal fluids, urine, tears, sweat, etc. Even with significant advances in diagnostic technology, many patients with suspected infections receive empiric antimicrobial therapy rather than appropriate treatment, which is driven by rapid identification of the infectious agent, leading to increased antimicrobial resistance. To positively impact healthcare, new tests are needed that are pathogen-specific, easy to use, and produce results quickly. Molecularly imprinted polymer (MIP)-based biosensors can achieve these general goals and have enormous potential for disease detection. This article aimed to overview recent articles dedicated to electrochemical sensors modified with MIP to detect protein-based biomarkers of certain infectious diseases in human beings, particularly the biomarkers of infectious diseases, such as HIV-1, COVID-19, Dengue virus, and others. Some biomarkers, such as C-reactive protein (CRP) found in blood tests, are not specific for a particular disease but are used to identify any inflammation process in the body and are also under consideration in this review. Other biomarkers are specific to a particular disease, e.g., SARS-CoV-2-S spike glycoprotein. This article analyzes the development of electrochemical sensors using molecular imprinting technology and the used materials' influence. The research methods, the application of different electrodes, the influence of the polymers, and the established detection limits are reviewed and compared.

From Synthesis to Clinical Trial: Novel Bioinductive Calcium Deficient HA/ß-TCP Bone Grafting Nanomaterial.

Maxillary sinus augmentation is a commonly used procedure for the placement of dental implants. However, the use of natural and synthetic materials in this procedure has resulted in postoperative complications ranging from 12% to 38%. To address this issue, we developed a novel calcium deficient HA/ß-TCP bone grafting nanomaterial using a two-step synthesis method with appropriate structural and chemical parameters for sinus lifting applications. We demonstrated that our nanomaterial exhibits high biocompatibility, enhances cell proliferation, and stimulates collagen expression. Furthermore, the degradation of ß-TCP in our nanomaterial promotes blood clot formation, which supports cell aggregation and new bone growth. In a clinical trial involving eight cases, we observed the formation of compact bone tissue 8 months after the operation, allowing for the successful installation of dental implants without any early postoperative complications. Our results suggest that our novel bone grafting nanomaterial has the potential to improve the success rate of maxillary sinus augmentation procedures.

Development of molecularly imprinted polymer based phase boundaries for sensors design (review).

Achievements in polymer chemistry enables to design artificial phase boundaries modified by imprints of selected molecules and some larger structures. These structures seem very useful for the design of new materials suitable for affinity chromatography and sensors. In this review, we are overviewing the synthesis of molecularly imprinted polymers (MIPs) and the applicability of these MIPs in the design of affinity sensors. Such MIP-based layers or particles can be used as analyte-recognizing parts for sensors and in some cases they can replace very expensive compounds (e.g.: antibodies, receptors etc.), which are recognizing analyte. Many different polymers can be used for the formation of MIPs, but conducing polymers shows the most attractive capabilities for molecular-imprinting by various chemical compounds. Therefore, the application of conducting polymers (e.g.: polypyrrole, polyaniline, polythiophene, poly(3,4-ethylenedioxythiophene), and ortho-phenylenediamine) seems very promising. Polypyrrole is one of the most suitable for the development of MIP-based structures with molecular imprints by analytes of various molecular weights. Overoxiation of polypyrrole enables to increase the selectivity of polypyrrole-based MIPs. Methods used for the synthesis of conducting polymer based MIPs are overviewed. Some methods, which are applied for the transduction of analytical signal, are discussed, and challenges and new trends in MIP-technology are foreseen.

Biosensors Based on Bio-Functionalized Semiconducting Metal Oxides.

Immobilization of biomaterials is a very important task in the development of biofuel cells and biosensors. Some semiconducting metal-oxide-based supporting materials can be used in these bioelectronics-based devices. In this article, we are reviewing some functionalization methods that are applied for the immobilization of biomaterials. The most significant attention is paid to the immobilization of biomolecules on the surface of semiconducting metal oxides. The improvement of biomaterials immobilization on metal oxides and analytical performance of biosensors by coatings based on conducting polymers, self-assembled monolayers and lipid membranes is discussed.

Electrochemical molecularly imprinted polymer based sensors for pharmaceutical and biomedical applications (review).

Recent challenges in the pharmaceutical and biomedical fields require the development of new analytical methods. Therefore, the development of new sensors is a very important task. In this paper, we are outlining the development of molecularly imprinted polymer (MIP) based sensors, which belongs to important branch of affinity sensors. In this review, recent advances in the design of MIP-based sensors are overviewed. MIPs-based sensing structures can replace expensive natural affinity compounds such as receptors or antibodies. Among many different polymers, conducting polymers show the most versatile properties, which are suitable for sensor application. Therefore, significant attention is paid towards MIPs based on conducting polymers, namely polypyrrole, polythiophene, poly(3,4-ethylenedioxythiophene), polyaniline and ortho-phenylenediamine. Moreover, many other materials, which could be imprinted analyte molecules, are overviewed. Among many conducting polymers, polypyrrole is highlighted as one of the most suitable for molecular imprinting. Some attention is dedicated to overview polymerization methods applied for the design of sensing structures used in various affinity sensors. The transduction of analytical signal is an important issue, therefore, physicochemical methods suitable for analytical signal transduction are also outlined. Advances, trends and perspectives in MIP application are discussed.

Microbial Fuel Cell Based on Nitrogen-Fixing Rhizobium anhuiense Bacteria.

In this study, the nitrogen-fixing, Gram-negative soil bacteria Rhizobium anhuiense was successfully utilized as the main biocatalyst in a bacteria-based microbial fuel cell (MFC) device. This research investigates the double-chambered, H-type R. anhuiense-based MFC that was operated in modified Norris medium (pH = 7) under ambient conditions using potassium ferricyanide as an electron acceptor in the cathodic compartment. The designed MFC exhibited an open-circuit voltage (OCV) of 635 mV and a power output of 1.07 mW m-2 with its maximum power registered at 245 mV. These values were further enhanced by re-feeding the anode bath with 25 mM glucose, which has been utilized herein as the main carbon source. This substrate addition led to better performance of the constructed MFC with a power output of 2.59 mW m-2 estimated at an operating voltage of 281 mV. The R. anhuiense-based MFC was further developed by improving the charge transfer through the bacterial cell membrane by applying 2-methyl-1,4-naphthoquinone (menadione, MD) as a soluble redox mediator. The MD-mediated MFC device showed better performance, resulting in a slightly higher OCV value of 683 mV and an almost five-fold increase in power density to 4.93 mW cm-2. The influence of different concentrations of MD on the viability of R. anhuiense bacteria was investigated by estimating the optical density at 600 nm (OD600) and comparing the obtained results with the control aliquot. The results show that lower concentrations of MD, ranging from 1 to 10 µM, can be successfully used in an anode compartment in which R. anhuiense bacteria cells remain viable and act as a main biocatalyst for MFC applications.

Assessment of Rhizobium anhuiense Bacteria as a Potential Biocatalyst for Microbial Biofuel Cell Design.

The development of microbial fuel cells based on electro-catalytic processes is among the novel topics, which are recently emerging in the sustainable development of energetic systems. Microbial fuel cells have emerged as unique biocatalytic systems, which transform the chemical energy accumulated in renewable organic fuels and at the same time reduce pollution from hazardous organic compounds. However, not all microorganisms involved in metabolic/catalytic processes generate sufficient redox potential. In this research, we have assessed the applicability of the microorganism Rhizobium anhuiense as a catalyst suitable for the design of microbial fuel cells. To improve the charge transfer, several redox mediators were tested, namely menadione, riboflavin, and 9,10-phenanthrenequinone (PQ). The best performance was determined for a Rhizobium anhuiense-based bio-anode mediated by menadione with a 0.385 mV open circuit potential and 5.5 µW/cm2 maximal power density at 0.35 mV, which generated 50 µA/cm2 anode current at the same potential.

Charge Transfer and Biocompatibility Aspects in Conducting Polymer-Based Enzymatic Biosensors and Biofuel Cells.

Charge transfer (CT) is a very important issue in the design of biosensors and biofuel cells. Some nanomaterials can be applied to facilitate the CT in these bioelectronics-based devices. In this review, we overview some CT mechanisms and/or pathways that are the most frequently established between redox enzymes and electrodes. Facilitation of indirect CT by the application of some nanomaterials is frequently applied in electrochemical enzymatic biosensors and biofuel cells. More sophisticated and still rather rarely observed is direct charge transfer (DCT), which is often addressed as direct electron transfer (DET), therefore, DCT/DET is also targeted and discussed in this review. The application of conducting polymers (CPs) for the immobilization of enzymes and facilitation of charge transfer during the design of biosensors and biofuel cells are overviewed. Significant attention is paid to various ways of synthesis and application of conducting polymers such as polyaniline, polypyrrole, polythiophene poly(3,4-ethylenedioxythiophene). Some DCT/DET mechanisms in CP-based sensors and biosensors are discussed, taking into account that not only charge transfer via electrons, but also charge transfer via holes can play a crucial role in the design of bioelectronics-based devices. Biocompatibility aspects of CPs, which provides important advantages essential for implantable bioelectronics, are discussed.

Advances in Molecularly Imprinted Polymers Based Affinity Sensors (Review).

Recent challenges in biomedical diagnostics show that the development of rapid affinity sensors is very important issue. Therefore, in this review we are aiming to outline the most important directions of affinity sensors where polymer-based semiconducting materials are applied. Progress in formation and development of such materials is overviewed and discussed. Some applicability aspects of conducting polymers in the design of affinity sensors are presented. The main attention is focused on bioanalytical application of conducting polymers such as polypyrrole, polyaniline, polythiophene and poly(3,4-ethylenedioxythiophene) ortho-phenylenediamine. In addition, some other polymers and inorganic materials that are suitable for molecular imprinting technology are also overviewed. Polymerization techniques, which are the most suitable for the development of composite structures suitable for affinity sensors are presented. Analytical signal transduction methods applied in affinity sensors based on polymer-based semiconducting materials are discussed. In this review the most attention is focused on the development and application of molecularly imprinted polymer-based structures, which can replace antibodies, receptors, and many others expensive affinity reagents. The applicability of electrochromic polymers in affinity sensor design is envisaged. Sufficient biocompatibility of some conducting polymers enables to apply them as "stealth coatings" in the future implantable affinity-sensors. Some new perspectives and trends in analytical application of polymer-based semiconducting materials are highlighted.