Transitioning from Supramolecular Chemistry to Molecularly Imprinted Polymers in Chemical Sensing.

This perspective article focuses on the overwhelming significance of molecular recognition in biological processes and its emulation in synthetic molecules and polymers for chemical sensing. The historical journey, from early investigations into enzyme catalysis and antibody-antigen interactions to Nobel Prize-winning breakthroughs in supramolecular chemistry, emphasizes the development of tailored molecular recognition materials. The discovery of supramolecular chemistry and molecular imprinting, as a versatile method for mimicking biological recognition, is discussed. The ability of supramolecular structures to develop selective host-guest interactions and the flexible design of molecularly imprinted polymers (MIPs) are highlighted, discussing their applications in chemical sensing. MIPs, mimicking the selectivity of natural receptors, offer advantages like rapid synthesis and cost-effectiveness. Finally, addressing major challenges in the field, this article summarizes the advancement of molecular recognition-based systems for chemical sensing and their transformative potential.

Selective Detection of Erythrocytes with QCMs-ABO Blood Group Typing.

Blood transfusion, as well as organ transplantation, is only possible after prior blood group (BG) typing and crossmatching. The most important blood group system is that of Landsteiner's ABO classification based on antigen presence on the erythrocyte surfaces. A mass sensitive QCM (quartz crystal microbalance) sensor for BG typing has been developed by utilizing molecular imprinting technology. Polyvinylpyrrolidone (crosslinked with N,N-methylenebisacrylamide) is a favorable coating that was imprinted with erythrocytes of different blood groups. In total, 10 MHz quartz sheets with two resonators, one for MIP (molecularly imprinted polymer) and the other for NIP (non-imprinted polymer) were fabricated and later used for mass-sensitive measurements. The structure of erythrocyte imprints resembles a donut, as identified by AFM (atomic force microscope). All the erythrocytes of the ABO system were chosen as templates and the responses to these selective coatings were evaluated against all blood groups. Each blood group can be characterized by the pattern of responses in an unambiguous way. The results for blood group O are remarkable given that all types of erythrocytes give nearly the same result. This can be easily understood as blood group O does not possess neither antigen A nor antigen B. The responses can be roughly related to the number of respective antigens on the erythrocyte surface. The imprints generate hollows, which are used for reversible recognition of the erythrocytes. This procedure is based on molecular recognition (based on supramolecular strategies), which results from size, shape and enthalpic interactions between host and guest molecules.

An Overview of High Frequency Acoustic Sensors-QCMs, SAWs and FBARs-Chemical and Biochemical Applications.

Acoustic devices have found wide applications in chemical and biosensing fields owing to their high sensitivity, ruggedness, miniaturized design and integration ability with on-field electronic systems. One of the potential advantages of using these devices are their label-free detection mechanism since mass is the fundamental property of any target analyte which is monitored by these devices. Herein, we provide a concise overview of high frequency acoustic transducers such as quartz crystal microbalance (QCM), surface acoustic wave (SAW) and film bulk acoustic resonators (FBARs) to compare their working principles, resonance frequencies, selection of piezoelectric materials for their fabrication, temperature-frequency dependency and operation in the liquid phase. The selected sensor applications of these high frequency acoustic transducers are discussed primarily focusing on the two main sensing domains, i.e., biosensing for working in liquids and gas/vapor phase sensing. Furthermore, the sensor performance of high frequency acoustic transducers in selected cases is compared with well-established analytical tools such as liquid chromatography mass spectrometry (LC-MS), gas chromatographic (GC) analysis and enzyme-linked immunosorbent assay (ELISA) methods. Finally, a general comparison of these acoustic devices is conducted to discuss their strengths, limitations, and commercial adaptability thus, to select the most suitable transducer for a particular chemical/biochemical sensing domain.

Molecular Imprinting and Functional Polymers for All Transducers and Applications.

The main challenge in developing a chemical sensor is the synthesis of recognition coatings, which are very sensitive and selective to analytes of interest. Molecular imprinting has proven to be the most innovative strategy for this purpose in functional polymer design in the last few decades. Moreover, the introduction of functional groups brings about new applications for all available transducers. Sensitivity and selectivity features of sensor coatings can be tuned by this approach. The strategy produces molecular cavities and interaction sites in sensor coatings. The synthesis of these tailored recognition materials is performed in an outstanding manner, saving time and the high costs of chemicals. Furthermore, intermolecular interactions between the analyte and chemical layers will generate sites that are complementary to the analyte. This procedure can easily be done, directly on a transducer surface, which entails engulfing the analyte by a prepolymer and crosslinking the polymeric material. These imprinted polymers form a robust recognition layer on the transducer surface, which cannot be peeled off and can withstand very harsh conditions, both in gaseous and liquid media. These recognition materials are very suitable, for small molecules and even large bioparticles.

Conductometric Sensor for PAH Detection with Molecularly Imprinted Polymer as Recognition Layer.

A conductometric sensor based on screen-printed interdigital gold electrodes on glass substrate coated with molecularly imprinted polyurethane layers was fabricated to detect polycyclic aromatic hydrocarbons (PAHs) in water. The results prove that screen-printed interdigital electrodes are very suitable transducers to fabricate low-cost sensor systems for measuring change in resistance of PAH-imprinted layers while exposing to different PAHs. The sensor showed good selectivity to its templated molecules and high sensitivity with a detection limit of 1.3 nmol/L e.g., for anthracene in water which is lower than WHO's permissible limit.

Surface Acoustic Wave (SAW) for Chemical Sensing Applications of Recognition Layers.

Surface acoustic wave (SAW) resonators represent some of the most prominent acoustic devices for chemical sensing applications. As their frequency ranges from several hundred MHz to GHz, therefore they can record remarkably diminutive frequency shifts resulting from exceptionally small mass loadings. Their miniaturized design, high thermal stability and possibility of wireless integration make these devices highly competitive. Owing to these special characteristics, they are widely accepted as smart transducers that can be combined with a variety of recognition layers based on host-guest interactions, metal oxide coatings, carbon nanotubes, graphene sheets, functional polymers and biological receptors. As a result of this, there is a broad spectrum of SAW sensors, i.e., having sensing applications ranging from small gas molecules to large bio-analytes or even whole cell structures. This review shall cover from the fundamentals to modern design developments in SAW devices with respect to interfacial receptor coatings for exemplary sensor applications. The related problems and their possible solutions shall also be covered, with a focus on emerging trends and future opportunities for making SAW as established sensing technology.

Graphene Hybrid Materials in Gas Sensing Applications.

Graphene, a two dimensional structure of carbon atoms, has been widely used as a material for gas sensing applications because of its large surface area, excellent conductivity, and ease of functionalization. This article reviews the most recent advances in graphene hybrid materials developed for gas sensing applications. In this review, synthetic approaches to fabricate graphene sensors, the nano structures of hybrid materials, and their sensing mechanism are presented. Future perspectives of this rapidly growing field are also discussed.

Blood Group Typing: From Classical Strategies to the Application of Synthetic Antibodies Generated by Molecular Imprinting.

Blood transfusion requires a mandatory cross-match test to examine the compatibility between donor and recipient blood groups. Generally, in all cross-match tests, a specific chemical reaction of antibodies with erythrocyte antigens is carried out to monitor agglutination. Since the visual inspection is no longer useful for obtaining precise quantitative information, therefore there is a wide variety of different technologies reported in the literature to recognize the agglutination reactions. Despite the classical methods, modern biosensors and molecular blood typing strategies have also been considered for straightforward, accurate and precise analysis. The interfacial part of a typical sensor device could range from natural antibodies to synthetic receptor materials, as designed by molecular imprinting and which is suitably integrated with the transducer surface. Herein, we present a comprehensive overview of some selected strategies extending from traditional practices to modern procedures in blood group typing, thus to highlight the most promising approach among emerging technologies.

Biomimetic receptors and sensors.

In biomimetics, living systems are imitated to develop receptors for ions, molecules and bioparticles. The most pertinent idea is self-organization in analogy to evolution in nature, which created the key-lock principle. Today, modern science has been developing host-guest chemistry, a strategy of supramolecular chemistry for designing interactions of analytes with synthetic receptors. This can be realized, e.g., by self-assembled monolayers (SAMs) or molecular imprinting. The strategies are used for solid phase extraction (SPE), but preferably in developing recognition layers of chemical sensors.

Biomimetic receptors for bioanalyte detection by quartz crystal microbalances - from molecules to cells.

A universal label-free detection of bioanalytes can be performed with biomimetic quartz crystal microbalance (QCM) coatings prepared by imprinting strategies. Bulk imprinting was used to detect the endocrine disrupting chemicals (EDCs) known as estradiols. The estrogen 17ß-estradiol is one of the most potent EDCs, even at very low concentrations. A highly sensitive, selective and robust QCM sensor was fabricated for real time monitoring of 17ß-estradiol in water samples by using molecular imprinted polyurethane. Optimization of porogen (pyrene) and cross-linker (phloroglucinol) levels leads to improved sensitivity, selectivity and response time of the estradiol sensor. Surface imprinting of polyurethane as sensor coating also allowed us to generate interaction sites for the selective recognition of bacteria, even in a very complex mixture of interfering compounds, while they were growing from their spores in nutrient solution. A double molecular imprinting approach was followed to transfer the geometrical features of natural bacteria onto the synthetic polymer to generate biomimetic bacteria. The use of biomimetic bacteria as template makes it possible to prepare multiple sensor coatings with similar sensitivity and selectivity. Thus, cell typing, e.g., differentiation of bacteria strains, bacteria growth profile and extent of their nutrition, can be monitored by biomimetic mass sensors. Obviously, this leads to controlled cell growth in bioreactors.

Natural and biomimetic materials for the detection of insulin.

Microgravimetric sensors have been developed for detection of insulin by using quartz crystal microbalances as transducers, in combination with sensitive layers. Natural antibodies as coatings were compared with biomimetic materials to fabricate mass-sensitive sensors. For this purpose polyurethane was surface imprinted by insulin, which acts as a synthetic receptor for reversible analyte inclusion. The sensor responses for insulin give a pronounced concentration dependence, with a detection limit down to 1 µg/mL and below. Selectivity studies reveal that these structured polymers lead to differentiation between insulin and glargine. Moreover, antibody replicae were generated by a double imprinting process. Thus, biological recognition capabilities of immunoglobulins are transferred to synthetic polymers. In the first step, natural-immunoglobulin-imprinted nanoparticles were synthesized. Subsequently, these templated particles were utilized for creating positive images of natural antibodies on polymer layers. These synthetic coatings, which are more robust than natural analogues, can be produced in large amount. These biomimetic sensors are useful in the biotechnology of insulin monitoring.

Monitoring automotive oil degradation: analytical tools and onboard sensing technologies.

Engine oil experiences a number of thermal and oxidative phases that yield acidic products in the matrix consequently leading to degradation of the base oil. Generally, oil oxidation is a complex process and difficult to elucidate; however, the degradation pathways can be defined for almost every type of oil because they mainly depend on the mechanical status and operating conditions. The exact time of oil change is nonetheless difficult to predict, but it is of great interest from an economic and ecological point of view. In order to make a quick and accurate decision about oil changes, onboard assessment of oil quality is highly desirable. For this purpose, a variety of physical and chemical sensors have been proposed along with spectroscopic strategies. We present a critical review of all these approaches and of recent developments to analyze the exact lifetime of automotive engine oil. Apart from their potential for degradation monitoring, their limitations and future perspectives have also been investigated.

QCM gas phase detection with ceramic materials--VOCs and oil vapors.

Titanate sol-gel layers imprinted with carbonic acids were used as sensitive layers on quartz crystal microbalance. These functionalized ceramics enable us detection of volatile organic compounds such as ethanol, n-propanol, n-butanol, n-hexane, n-heptane, n-/iso-octane, and n-decane. Variation of the precursors (i.e., tetrabutoxy titanium, tetrapropoxy titanium, tetraethoxy titanium) allows us to tune the sensitivity of the material by a factor of 7. Sensitivity as a function of precursors leads to selective inclusion of n-butanol vapors down to 1 ppm. The selectivity of materials is optimized to differentiate between isomers, e.g., n- and iso-octane. The results can be rationalized by correlating the sensor effects of hydrocarbons with the Wiener index. A mass-sensitive sensor based on titanate layer was also developed for monitoring emanation of degraded engine oil. Heating the sensor by a meander avoids vapor condensation. Thus, a continuously working oil quality sensor was designed.

Dual and tetraelectrode QCMs using imprinted polymers as receptors for ions and neutral analytes.

Polymers as coating materials were combined with quartz crystal microbalances (QCMs) to design sensor devices for the detection of both ionic and neutral analytes in liquid phase. The design and geometry of dual and tetraelectrode QCMs have been optimized to reduce electric field interferences. An unusual Sauerbrey effect was observed while exposing potassium salt solution to 10- and 20-MHz QCMs, i.e. increase in the frequency shifts by a factor of seven, which is attributed to electro-acoustic phenomena. Non-functionalized sol-gel materials were synthesized by templating with hydrophobic salt such as tetraethyl ammonium picrate. Imprinting with these ions of low charge density leads to sensitive layers, and UV-Vis spectroscopy was used to check re-inclusion of this analyte. In the next strategy, functionalized polyurethane for potassium ions and sol-gel materials with aminopropyl group as ligand were generated to tune selectivity and sensitivity towards Ni(2+) and Cu(2+). Methacrylic acid polymers were optimized for the detection of atrazine by hydrogen bonding; double molecular imprinted polyurethane approach was followed for pyrene recognition. Finally, these imprinted polymers were combined with tetraelectrode QCM to develop sensor platform.

Conductometric sensors for monitoring degradation of automotive engine oil.

Conductometric sensors have been fabricated by applying imprinted polymers as receptors for monitoring engine oil quality. Titania and silica layers are synthesized via the sol-gel technique and used as recognition materials for acidic components present in used lubricating oil. Thin-film gold electrodes forming an interdigitated structure are used as transducers to measure the conductance of polymer coatings. Optimization of layer composition is carried out by varying the precursors, e.g., dimethylaminopropyltrimethoxysilane (DMAPTMS), and aminopropyl-triethoxysilane (APTES). Characterization of these sensitive materials is performed by testing against oil oxidation products, e.g., carbonic acids. The results depict that imprinted aminopropyltriethoxysilane (APTES) polymer is a promising candidate for detecting the age of used lubricating oil. In the next strategy, polyurethane-nanotubes composite as sensitive material is synthesized, producing appreciable differentiation pattern between fresh and used oils at elevated temperature with enhanced sensitivity.

Solvent vapour detection with cholesteric liquid crystals--optical and mass-sensitive evaluation of the sensor mechanism.

Cholesteric liquid crystals (CLCs) are used as sensitive coatings for the detection of organic solvent vapours for both polar and non-polar substances. The incorporation of different analyte vapours in the CLC layers disturbs the pitch length which changes the optical properties, i.e., shifting the absorption band. The engulfing of CLCs around non-polar solvent vapours such as tetrahedrofuran (THF), chloroform and tetrachloroethylene is favoured in comparison to polar ones, i.e., methanol and ethanol. Increasing solvent vapour concentrations shift the absorbance maximum to smaller wavelengths, e.g., as observed for THF. Additionally, CLCs have been coated on acoustic devices such as the quartz crystal microbalance (QCM) to measure the frequency shift of analyte samples at similar concentration levels. The mass effect for tetrachloroethylene was about six times higher than chloroform. Thus, optical response can be correlated with intercalation in accordance to mass detection. The mechanical stability was gained by combining CLCs with imprinted polymers. Therefore, pre-concentration of solvent vapours was performed leading to an additional selectivity.

QCM-arrays for sensing terpenes in fresh and dried herbs via bio-mimetic MIP layers.

A piezoelectric 10 MHz multichannel quartz crystal microbalance (MQCM), coated with six molecularly imprinted polystyrene artificial recognition membranes have been developed for selective quantification of terpenes emanated from fresh and dried Lamiaceae family species, i.e., rosemary (Rosmarinus Officinalis L.), basil (Ocimum Basilicum) and sage (Salvia Officinalis). Optimal e-nose parameters, such as layer heights (1-6 KHz), sensitivity <20 ppm of analytes, selectivity at 50 ppm of terpenes, repeatability and reproducibility were thoroughly adjusted prior to online monitoring. Linearity in reversible responses over a wide concentration range <20-250 ppm has been achieved. Discrimination between molecules of similar molar masses, even for isomers, e.g. α-pinene and ß-pinene is possible. The array has proven its sensitive and selective properties of sensor responses (20-1,200 Hz) for the difference of fresh and dried herbs. The sensor data attained was validated by GC-MS, to analyze the profiles of sensor emanation patterns. The shelf-life of herbs was monitored via emanation of organic volatiles during a few days. Such an array in association with data analysis tools can be utilized for characterizing complex mixtures.

Detection of viruses with molecularly imprinted polymers integrated on a microfluidic biochip using contact-less dielectric microsensors.

Rapid detection of viral contamination remains a pressing issue in various fields related to human health including clinical diagnostics, the monitoring of food-borne pathogens, the detection of biological warfare agents as well as in viral clearance studies for biopharmaceutical products. The majority of currently available assays for virus detection are expensive, time-consuming, and labor-intensive. In the present work we report the creation of a novel micro total analysis system (microTAS) capable of continuously monitoring viral contamination with high sensitivity and selectivity. The specific interaction between shape and surface chemistry between molecular imprinted polymer (MIP) and virus resulted in the elimination of non-specific interaction in the present sensor configuration. The additional integration of the blank (non-imprinted) polymer further allowed for the identification of non-specific adsorption events. The novel combination of microfluidics containing integrated native polymer and MIP with contact-less dielectric microsensors is evaluated using the Tobacco Mosaic Virus (TMV) and the Human Rhinovirus serotype 2 (HRV2). Results show that viral binding and dissociation events can be readily detected using contact-less bioimpedance spectroscopy optimized for specific frequencies. In the present study optimum sensor performance was achieved at 203 kHz within the applied frequency range of 5-500 kHz. Complete removal of the virus from the MIP and device reusability is successfully demonstrated following a 50-fold increase in fluid velocity. Evaluation of the microfluidic biochip revealed that microchip technology is ideally suited to detect a broader range of viral contaminations with high sensitivity by selectively adjusting microfluidic conditions, sensor geometries and choice of MIP polymeric material.

Sensing picornaviruses using molecular imprinting techniques on a quartz crystal microbalance.

Molecular imprinting techniques were adapted to design a sensor for the human rhinovirus (HRV) and the foot-and-mouth disease virus (FMDV), which are two representatives of picornaviruses. Stamp imprinting procedures lead to patterned polyurethane layers that depict the geometrical features of the template virus, as confirmed by AFM for HRV. Quartz crystal microbalance (QCM) measurements show that the resulting layers incorporate the template viruses reversibly and lead to mass effects that are almost an order of magnitude higher than those of nonspecific adsorption. Thus, for example, the sensor yields a net frequency effect of -300 Hz when applying a virus suspension with a concentration of approximately 100 microg/mL with an excellent signal-to-noise ratio. The cavities are not only selective to shape but also to surface chemistry: different HRV serotypes (HRV1A, HRV2, HRV14, and HRV16, respectively) can be distinguished with the sensor materials by a selectivity factor of 3, regardless of the group (major/minor) to which they belong. The same selectivity factor can be observed between HRV and FMDV. Hence, imprinting leads to an "artificial antibody" toward viruses, which does not only recognize their receptor binding sites, but rather detects the whole virus as an entity. Brunauer-Emmett-Teller (BET) studies allow simulation of the sensor characteristics and reveal the number of favorable binding sites in the coatings.

Application of yeast imprinting in biotechnology and process control.

Rapid advancements in biotechnology depend on the development of reliable sensing sytems adaptable to a variety of analytes. Molecularly imprinted polymers combined with mass-sensitive devices (10 MHz QCMs) provide a reliable and robust method to observe cell growth and allow cell specifications in real-time. Such biosensors selectively detect fermenting yeast in a complex matrix and 10(4) cells/microl in solution correspond to an adhesion of approximately 3 x 10(3) cells on the sensor coating. Over a period of up to 40 hours, the growth of the microorganism at 30 degrees C was observed in various nutrient solutions of glucose, peptone and ammonium sulfate, thereby rendering the determination of optimum growth conditions possible. While almost no change, i.e. no cell propagation, occurred in the absence of glucose, the frequency decreases to more than 700 Hz under rich conditions. Increasing the depth of the imprints to more than 1.5 microm the yeast cells are so strongly bound that they are fixed in the material. With such gravimetric sensors, for instance osmotic effects of cells can be followed by a frequency change of 3 kHz by altering the ion strength by 0.1 M.