Construction and application of molecular imprinting-based surface-enhanced Raman scattering sensors

Molecularly imprinted polymers (MIPs) prepared by molecular imprinting technology (MIT) are polymers with specific recognition sites matching the shape, size and functional groups of template molecules, which can selectively identify and enrich target analytes (template molecules), and have been widely used in sample pretreatment, chemical/biological sensing and other fields. However, in the processes of preparation and applications of MIPs, there are still some problems, such as difficult elution of template molecules, fewer effective recognition sites, low binding capacity, low mass transfer rate and poor recognition in aqueous media. As a multidisciplinary technology, MIT has developed rapidly by borrowing and integrating related advanced technologies/strategies of other fields. Consequently, a variety of new imprinting technologies and strategies have continuously emerged, which not only effectively solve the abovementioned problems but also push forwards the development of novel MIPs and widen their applications. In this paper, orienting the applications of MIPs in sample pretreatment, sensors and stimuli responses, some advanced preparation technologies and strategies for MIPs materials are highlighted, including ingenious imprinting technologies (surface imprinting, nanoimprinting; controlled/living polymerization, solid-phase synthesis, etc.), special imprinting strategies (multi-template/monomer imprinting, dummy imprinting, boronate affinity imprinting, etc.), and stimuli-responsive imprinting (magnetic, temperature, pH responsive, etc.). Fundamental features of the advanced imprinting technologies/strategies and their utilizations for MIPs preparations along with representative applications are described in details, involving important issues and research challenges. Firstly, a comprehensive overview of main imprinting technologies and strategies for MIPs preparation in sample pretreatment application is provided. In this regard, MIPs are used as selective adsorbents of various extraction technologies such as solid-phase extraction (SPE), dispersive SPE and magnetic SPE. Aiming at high selectivity and high adsorption capacity, the MIPs should have ideal morphology, uniform size and excellent surface properties. Besides conventional preparative methods, it is required to introduce new imprinting technologies and strategies, mainly including the ingenious imprinting technologies of surface imprinting, nanoimprinting, controlled/living free radical polymerization (CLRP), click chemistry, hollow porous polymer synthesis technology and solid-phase synthesis, and the special imprinting strategies of multi-template/monomer imprinting, dummy/segment imprinting, magnetic material and boronate affinity imprinting. Surface imprinting and nanoimprinting technologies are usually adopted by coupling with the abovementioned imprinting technologies and strategies. Secondly, advanced imprinting technologies and strategies for the construction of MIPs-based sensors are summarized. For the sensors, the MIPs as recognition elements can specifically bind target analytes and as transduction elements can generate output signals for detection. Typically, the output detection signals can be classified into three types, electrochemical, optical and piezoelectric types according to the transduction mechanism; molecular imprinting based electrochemistry, fluorescence and surface enhanced Raman scattering sensors are the research hotspots. For sensing applications, it is necessary to consider the main parameters such as response time, linear dynamic range, sensitivity, selectivity and reproducibility. Therefore, the MIPs should have excellent interface properties by employing appropriate preparative technologies and strategies. Nanoimprinting, surface imprinting and composite material imprinting strategy have become the preferences. Herein, constructions of molecular imprinting fluorescence sensors are emphatically introduced, especially ratiometric fluorescence ones. Thirdly, the imprinting technologies and strategies orienting stimuli-responsive application are briefly introduced, for preparing stimuli-responsive MIPs (SR-MIPs) with specific recognition ability toward targeted molecules under stimuli-regulation and thereby achieving intelligent control. SR-MIPs are able to sensitively respond to specific external physicochemical/biological stimuli with a considerable and reversible change in their properties, such as molecular chain structure, solubility, swelling or dissociation behavior, resulting in regular changes of imprinting properties. The most reported magnetic, temperature, photonic and pH sensitive SR-MIPs and their dual or multi stimuli responsive SR-MIPs are reviewed. The rapid development of smart ecofriendly SR-MIPs and their stimuli-responsive application will accelerate the drug delivery application and assist the widely carried out sample pretreatment and sensors applications. Lastly, future perspectives of MIT and MIPs are proposed. In order to solve the core issues of selectivity, mass transfer rate and adsorption capacity of MIPs, it is imperative to rationally combine various imprinting technologies and strategies. The ingenious fusion of MIT and various advanced technologies should be continuously strengthened to promote the preparation of MIPs materials.

分子印迹技术（molecular imprinting technology， MIT）借鉴抗体-抗原特异性识别机制，能够高度精准地对目标物质进行选择性萃取，在分离、检测等领域极具应用潜力。但传统MIT在材料制备、样品前处理及检测分析中存在诸多亟待解决的问题：制备的分子印迹聚合物（molecularly imprinted polymers，MIPs）存在印迹位点不均一、模板分子残留严重、机械性能差等缺陷；以MIPs为吸附剂的前处理方法因目标物选择吸附速率慢而耗时，且特异性识别性能有待提升；基于MIPs的检测手段灵敏度低，检测耗时长，难以现场实时监测。这些问题制约了MIT的发展与广泛应用。近些年，电场辅助技术与MIT结合为解决上述问题提供了有效策略。制备MIPs时，在聚合体系中引入电场，使带电模板分子与功能单体受电场力定向移动，促使单体更有序地围绕模板分子排列，从而制得印迹位点均匀、分子取向性良好的MIPs。在样品前处理过程中，外部电场所提供的电泳驱动力可提升MIPs对目标物的传质速率，缩短吸附与解吸时间，优化其特异性识别性能。此外，MIPs电化学传感器的发展及其与微流控技术的结合显著提升了MIPs在检测领域的实用性。本文重点阐述电场在MIPs制备、样品前处理及检测分析三大关键环节的具体应用与作用机制，总结电场辅助MIT在环境监测、生物医学、食品安全等领域的应用前景，并展望了未来发展方向。

Molecularly imprinted polymers (MIPs) receive extensive interest, owing to their structure predictability, recognition specificity, and application universality as well as robustness, simplicity, and inexpensiveness. Surface-enhanced Raman scattering (SERS) is regarded as an ideal optical detection candidate for its unique features of fingerprint recognition, nondestructive property, high sensitivity, and rapidity. Accordingly, MIP based SERS (MIP-SERS) sensors have attracted significant research interest for versatile applications especially in the field of chemo- and bioanalysis, showing excellent identification and detection performances. Herein, we comprehensively review the recent advances in MIP-SERS sensors construction and applications, including sensing principles and signal enhancement mechanisms, focusing on novel construction strategies and representative applications. First, the basic structure of the MIP-SERS sensors is briefly outlined. Second, novel imprinting strategies are highlighted, mainly including multifunctional monomer imprinting, dummy template imprinting, living/controlled radical polymerization, and stimuli-responsive imprinting. Third, typical application of MIP-SERS sensors in chemo/bioanalysis is summarized from both small and macromolecular aspects. Lastly, the challenges and perspectives of the MIP-SERS sensors are proposed, orienting sensitivity improvement and application expanding.

分子印迹聚合物(MIPs)是通过模拟酶与底物或抗原抗体特异性结合原理而制备的高分子聚合物,以其结构预定性、识别特异性、制备简便、成本低、耐受性强等优点而被广泛用于样品前处理、传感分析、生物医药、环境/食品分析等多个领域。目前已发展多种策略用于MIPs制备,达到简化制备过程或提高聚合物性能等目的,极大拓宽了MIPs的应用范围。对各种先进印迹策略及其组合使用的探索已成为MIPs制备的研究热点之一。其中,片段印迹策略和虚拟模板印迹策略备受青睐。片段印迹策略是选择目标分子中含有特定官能团的一部分(片段结构)作为模板进行印迹,通过对片段的识别达到对整个分子的识别,能够克服某些目标物不易获得或体积较大不适合作为模板的问题,为印迹易失活、易传染的目标物及整体印迹困难的大分子提供可行的方法。虚拟模板印迹策略是选用与目标物特异性结构相似或相同的其他物质代替目标物作为模板制备MIPs,可在很大程度上解决模板不易获得或较昂贵等问题,以及避免模板可能泄漏对结果造成的影响,尤其适用于目标物造价高、具有感染性、易燃易爆、易降解等不适合作为模板分子的情况。该文选取了最近4年发表在ACS、Elsevier、RSC等数据库约20篇相关文献,综述了片段/虚拟MIPs(FMIPs/DMIPs)的应用新进展。首先,针对蛋白质和微生物检测以及哺乳动物细胞印迹,介绍了FMIPs在生物医药领域的应用,另外介绍了FMIPs在食品分析领域的研究进展。随后,介绍了DMIPs在样品前处理和传感分析领域的应用。在样品前处理中,DMIPs主要作为固相萃取吸附剂进行装柱固相萃取、分散固相萃取、磁固相萃取、基质固相分散萃取等,或作为分子印迹膜材料,用于选择性萃取和富集分离样品中的目标分析物。在传感分析领域,DMIPs主要作为传感器的传感和转导元件,提高化学发光或荧光检测等方法的灵敏度和准确度。最后,对片段印迹和虚拟模板印迹策略的优缺点、区别与联系进行了总结,并展望了这两种策略的发展与应用前景。

极性农药包括杀菌剂、除草剂、杀虫剂等,种类丰富,成本低廉,在农业中应用广泛,其滥用易导致水资源和土壤等环境污染,人类通过间接接触动植物源性食品和环境中的极性农药残留也增加了农药暴露风险。极性农药的物理化学性质差异大,通常痕量存在于食品和环境样品等复杂基质中,这对其准确检测分析带来了挑战。分子印迹聚合物(MIPs)作为一种人工制备的选择性吸附剂,具有与模板分子在空间结构、大小尺寸和功能基团上互补的特定识别位点,且易于制备,成本低,稳定性好,重复利用率高,已被广泛用于极性农药残留的样品前处理和分析检测中。MIPs可以作为固相萃取(SPE)、固相微萃取(SPME)、磁性固相萃取(MSPE)、搅拌棒固相萃取(SBSE)等前处理方法的吸附剂,还可用于制备光、电、化学传感器,作为质谱检测的离子源基底和拉曼光谱的增强基底。目前针对极性农药残留的检测,已有许多研究报道了多种分子印迹材料用于高效分离分析各种复杂基质中的极性农药残留,但未见此方面的综述报道。该文首先介绍了MIPs的印迹策略、聚合策略,并针对传统MIPs制备和应用中存在的问题,简要概括了一些新型的分子印迹策略和制备技术;然后从极性农药残留分析的角度出发,总结归纳了分子印迹材料近年来特别是近5年来在各种极性农药残留(包括新烟碱类、有机磷类、三嗪类、唑类、脲类等)检测中的应用,并针对现存问题展望了其未来的发展方向和趋势。

Chiral drugs exert pharmacological effects through strict matching with chiral biological macromolecules and chiral recognition. Each enantiomer has different pharmacological activities, metabolic processes and rates, as well as toxicity pharmacokinetic characteristics owing to the difference in its interactions with the chiral environment. Therefore, method development for the resolution of chiral drugs is of great significance for the synthesis of chiral drugs and for quality control during the production process. Molecularly imprinted polymers (MIPs) are prepared by using a target molecule as the template. MIPs demonstrate highly specific recognition properties toward the target molecule since they have specific spatial molecular structures and functional groups. Hence, MIPs are particularly suitable for the separation and purification of chiral drugs. Capillary electrochromatography (CEC) offers the advantages of high separation efficiency and high selectivity owing to the dual separation mechanisms including capillary electrophoresis and liquid chromatography. By using MIPs as the stationary phases for CEC, the advantages of the two technologies can be combined to achieve efficient separation of chiral drugs. MIPs were first applied to CEC for chiral resolution in 1994, and since then, there have been notable advances in this field. The four main chiral separation modes in CEC involve the use of MIPs as the stationary phases of open tubular, packed, and monolithic columns, and as the pseudostationary phase in the separation medium. This review summarizes the research progress of these four methods and reveals the potential of MIPs in chiral resolution by CEC. The advantages and disadvantages of these methods are commented. MIPs as the stationary phases of packed columns can allow for chiral separation. However, the preparation of packed columns in narrow capillaries is difficult. In addition, frits must be prepared at the ends of the capillaries to seal the MIPs. The frits lead to the formation of bubbles during the CEC analysis, thus resulting in poor repeatability and stability. These problems can be overcome by using MIP-based open tubular columns. Furthermore, conditioning of open tubular columns is easy and less time-consuming. However, open tubular columns have limited capacity. MIP-based monolithic columns have greater capacity than do open tubular columns, and frits are not required in this case. However, in situ preparation of MIPs monolith in narrow capillaries is still challenging. The application of MIPs to chiral CEC can also be realized by using them as pseudostationary phases (additives) in the separation medium, and this allows for ease of operation. Moreover, the amount of MIPs introduced into the capillary can be accurately controlled. Thus, the batch-to-batch reproducibility can be improved, but this has the disadvantage of increased MIP consumption. In order to further expand the potential of MIPs in chiral CEC, the following aspects must be considered. First, improvement of the preparation method. In most reported MIP-based-chiral CEC techniques, the peaks of the imprinted molecules show severe tailing, and this problem must be resolved. Improving the mass transfer rate of the prepared MIPs may be a suitable solution in this regard. Second, development of new functional monomers. A functional monomer is an indispensable component in the preparation of MIPs. New functional monomers can be prepared according to the "three-point interaction" rule. Third, selection of template molecules. A single enantiomer of chiral drugs is used as the template molecule to prepare chiral MIPs. The method is not suitable for the preparation of MIPs of chiral drugs for which a single enantiomer is difficult to obtain. Therefore, appropriate choice of the template molecules for these drugs is imperative. Fourth, discussion of chiral separation mechanism. The mechanism of interaction between the template molecules and MIPs needs to be explored further, in order to obtain theoretical guidance for the design and preparation of chiral MIPs.

A Biosensor Combining Molecularly Imprinted Polymers (M-MIPs) and Surface Enhanced Raman Spectroscopy (SERS) to Detect Antibiotics in Food Samples   Yi Sun,1*, Jon Ashley1, Kaiyu Wu1, and Anja Bosen1. 1 Department of Micro- and Nanotechnology, Technical University of Denmark, Ørsteds Plads, DK-2800 Kgs. Lyngby, Denmark   * Email: sun.yi@nanotech.dtu.dk; Tel.: +45 45256319   In this study, temperature-responsive magnetic molecularly imprinted polymers (M-MIP) nanoparticles were synthesized for the first time for the extraction of cloxacillin in pork products. By combining the M-MIPs with surface enhanced Raman spectroscopy (SERS), a sensitive biosensor was demonstrated to detect cloxacillian with pico-mole sensitivity. MIPs are synthetic ligands which can be tailored to bind any analyte of choice1.  They are of great interest due to their thermal stability, robustness, low cost and comparable binding affinity. They have been used in sample preparation and biosensing as an attractive alternative to natural antibodies to capture targets ranging from small molecules to big proteins.   In this work, the magnetic nanoparticles with MIP-based receptors were synthesized for efficient and rapid extraction of antibiotic residues in pork samples.  Fe3O4 nanoparticles were obtained using the solvothermal synthesis.  The resultant nanoparticles were treated with Tetraethyl orthosilicate (TEOS) to form a SiO2 layer.  Finally a thin MIP layer was polymerized round the nanoparticles using azobisisobutyronitrile (AIBN) as the initiator, ethylene glycol dimethacrylate (EDGMA) as the cross-linker, N-isopropylmethacryamide (NIPAm), methacrylic acid (MAA) as the monomers and the antibiotic as the template.  By adding the monomer NIPAm, the MIPs become temperature responsive, and can swell at low temperature to release the target. The corresponding magnetic non-imprinted polymer nanoparticles (M-NIP) was prepared using the same method in the absence of the template. An Overview of the synthesis strategy is shown in Fig. 1. The resultant M-MIP nanoparticles were characterized using IR, XRD scanning electron microscopy (SEM) and transmission electron microscopy (TEM) (Fig. 2).  Both binding affinities of the resultant M-MIPs and M-NIPs were tested using UV absorbance (Fig. 3). M-MIPs with 300-400 nm in size and good binding capacities were obtained. To demonstrate the feasibility of using M-MIPs for sample preparation, the synthesized M-MIPs were mixed with pork blood samples spiked with Chloxacillian. After incubation at room temperature, the M-MIPs were collected using a magnet and washed by acetonitrile. Owing to the thermos-responsive properties of MIPs, Chloxacillian was easily released by cooling the MIPs to 4 degree. The collected Chloxacillian was dropped on a SERS substrate which contained an array of silicon micropillars coated with silver. The corresponding calibration plots showed a detection limit (LOD) of about 50 pmol (Fig. 4). The biosensor combining M-MIPs and SERS would be widely used on site or in the field for rapidly screening food contaminants to ensure food safety. Fig. 1: Overview of the synthesis of M-MIPs     Fig.2 IR characterization of Fe3O4, Fe3O4@SiO2, Fe3O4@ SiO2-MPA and, Fe3O4@SiO2-MIP; XRD of Fe3O4. Fig.3 (A) Binding kinetics and (B) Binding capacity of Cloxacillian MIPs and NIPs.                         Fig.4 SERS spectra of cloxacillin in MeOH:acetic acid (9:1) and corresponding calibration plots.   REFERENCES:   J. Ashley, M-A. Shahbazi, K. Kant, V. A. Chidambara, A.Wolff, D. D. Bang, Y. Sun, “Molecularly Imprinted Polymers for Sample Preparation and Biosensing in Food analysis: Progress and Perspectives, Biosens. Bioelectron. 2017, 91, 606-615.    

Molecular imprinting technology (MIT) concerns formation of selective sites in a polymer matrix with the memory of a template. Recently, molecularly imprinted polymers (MIPs) have aroused extensive attention and been widely applied in many fields, such as solid-phase extraction, chemical sensors and artificial antibodies owing to their desired selectivity, physical robustness, thermal stability, as well as low cost and easy preparation. With the rapid development of MIT as a research hotspot, it faces a number of challenges, involving biological macromolecule imprinting, heterogeneous binding sites, template leakage, incompatibility with aqueous media, low binding capacity and slow mass transfer, which restricts its applications in various aspects. This critical review briefly reviews the current status of MIT, particular emphasis on significant progresses of novel imprinting methods, some challenges and effective strategies for MIT, and highlighted applications of MIPs. Finally, some significant attempts in further developing MIT are also proposed (236 references).

Molecular Imprinting Technology (MIT) is a technique to design artificial receptors with a predetermined selectivity and specificity for a given analyte, which can be used as ideal materials in various application fields. Molecularly Imprinted Polymers (MIPs), the polymeric matrices obtained using the imprinting technology, are robust molecular recognition elements able to mimic natural recognition entities, such as antibodies and biological receptors, useful to separate and analyze complicated samples such as biological fluids and environmental samples. The scope of this review is to provide a general overview on MIPs field discussing first general aspects in MIP preparation and then dealing with various application aspects. This review aims to outline the molecularly imprinted process and present a summary of principal application fields of molecularly imprinted polymers, focusing on chemical sensing, separation science, drug delivery and catalysis. Some significant aspects about preparation and application of the molecular imprinting polymers with examples taken from the recent literature will be discussed. Theoretical and experimental parameters for MIPs design in terms of the interaction between template and polymer functionalities will be considered and synthesis methods for the improvement of MIP recognition properties will also be presented.

The sol-gel method demonstrates significant potential for fabricating protein molecularly imprinted polymers (MIPs). In order to maintain good protein structure and provide more recognition functional groups during the preparation of protein MIPs. In this study, an exceptionally mild sol-gel protocol for protein MIPs synthesis was developed, in which no catalyst or organic solvent was employed and abundant recognition groups were introduced through in-situ derivatization. This method has been applied in the preparation of MIPs using lysozyme (lys) as a template. The developed MIPs exhibit high adsorption capacity and selectivity toward lys. The generation of the imprinting effect was successfully demonstrated by observing the surface morphology and evaluating the physical/chemical properties of the synthesized MIPs. In subsequent adsorption experiments, MIPs also showed excellent adsorption performance (389.85 mg/g) and quickly reached the adsorption equilibrium within 60 min. In addition, the selectivity of MIPs for lys was improved by the sol-gel imprinting process, and good reusability was observed after five adsorption-desorption cycles. The method was also successfully applied to isolate lys from egg white samples. This work demonstrates the great potential of the sol-gel strategy in the field of molecular imprinting.

Molecularly imprinted polymers (MIP) exhibiting high selectivity and affinity tothe predetermined molecule (template) are now seeing a fast growing research. However,optimization of the imprinted products is difficult due to the fact that there are manyvariables to consider, some or all of which can potentially impact upon the chemical,morphological and molecular recognition properties of the imprinted materials. This reviewpresent a summary of the principal synthetic considerations pertaining to good practice in thepolymerization aspects of molecular imprinting, and is primarily aimed at researcher familiarwith molecular imprinting methods but with little or no prior experience in polymersynthesis. The synthesis, characteristic, effect of molecular recognition and differentpreparation methods of MIP in recent few years are discussed in this review, unsolvedproblems and possible developments of MIP were also been briefly discussed.

Trace analysis of food by surface-enhanced Raman spectroscopy combined with molecular imprinting technology: Principle, application, challenges, and prospects.

BackgroundCyanazine (CYZ) is one of the triazine herbicides to prevent broadleaf grass and weeds in crops. Despite its affordability and productivity in increasing crop yield, the extensive usage of CYZ contributes to environmental pollution and poses risks to living organisms. Most research has focused on detecting CYZ in the environment and its toxicity to humans and the ecosystem. For these reasons, molecular imprinting technology (MIT) can be applied to produce an effective adsorbent material of high binding affinity and selectivity towards its target compound which is known as molecularly imprinted polymers (MIPs). In this study, MIP was prepared by precipitation polymerization using CYZ as a template molecule, methacrylic acid (MAA), acrylamide (AAm) and 4-vinylpyridine (4VP) as functional monomers, and ethylene glycol dimethacrylate (EGDMA) as cross-linker in the ratio of 1:6:12, respectively. The effects of contact time, initial concentration, pH, and polymer dosages on the adsorption efficiencies of MIPs were also investigated in this study.ResultsMIPs of CYZ were successfully synthesized by precipitation polymerization method with a non-covalent approach using different functional monomers such as methacrylic acid (MAA), acrylamide (AAm) and 4-vinylpyridine (4VP). For the comparison study, the non-imprinted polymer (NIP) was synthesized without the addition of CYZ, the template molecule. The FTIR analysis indicated the interactions among CYZ and functional monomers (MAA, AAm or 4VP) in the presence of EGDMA as a cross-linker. The FESEM analysis showed that only MIP (AAm) and NIP (AAm) had regular and spherical polymer particles while MIP (MAA), NIP (MAA), MIP (4VP) and NIP (4VP) were agglomerated and irregular in shape. The EDX analysis showed that the MIPs were mainly composed of carbon and oxygen. Meanwhile, the BET analysis of MIP (AAm) had higher surface area, total pore volume and average pore radius than that NIP (AAm). Based on the batch binding study, MIP (AAm) (83.30%) had the highest binding efficiency than the MIP (MAA) (76.96%) and MIP (2VP) (76.90%) at a contact time of 240 min. The optimum conditions for the highest binding efficiency of MIP (AAm) were obtained at an initial concentration of 6 ppm, pH 7 and polymer dosage of 0.1 g polymer beads. The adsorption efficiency of MIP (AAm) with CYZ at the optimum parameters resulted in 86.39%. The selectivity test showed that MIP (AAm) was more selective towards CYZ than AME, the competitive compound with relative selectivity coefficient of 2.36. The kinetic isotherm of MIP (AAm) was best explained according to the pseudo-second-order kinetic model while the adsorption isotherm of MIP (AAm) was based on the Langmuir adsorption isotherm model. The MIP (AAm) was tested in the distilled water (DIW), tap water and river water spiked with CYZ and a substantial amount of CYZ was removed with a recovery of 86.67%, 84.75% and 84.69%, respectively.ConclusionThe MIPs of CYZ were successfully synthesized by the precipitation polymerization method using different functional monomers. Among those MIPs, MIP (AAm) showed the highest rebinding efficiency and therefore this MIP was selected for further studies. The best combination of CYZ, AAm was the main factor that contributed to the morphological and chemical properties, as well as the efficiency and selective binding performance of MIP (AAm). Since MIP (AAm) showed a substantial removal efficiency of CYZ in the environment specifically water sources, it has the capability to act as an adsorbent material for various purposes such as solid-phase extraction techniques and a stationary phase in various chromatographic techniques.Graphical

With the help of molecular imprinting technology, artificial receptors can be made and used for identification. This technique's limitless application increases polymer technology and makes it adaptable to other technologies. In this study, examples of sensor applications are used to explain molecular imprinting technology (MIT) and its brief history. MIT can be used to create polymer-based artificial receptors with remarkable selectivity and affinity to detect any target molecules that can be imprinted on a polymer. A monomer is synthesized around a template molecule to create a selective cavity that serves as an artificial receptor. Molecularly imprinted polymers (MIP) offer a wide range of uses and have recently garnered much attention. These polymers' production methods, production kinds, and molecular imprinting techniques are all thoroughly detailed. The outstanding properties of MIPs make a crucial contribution to sensor applications offering selective, fast, easy, and cost-effective analysis, which became very popular after Clark published his first biosensor study. Apart from the biological recognition receptors, MIPs have the advantage that they are not affected by physical conditions of the environment, such as temperature, pH, and ion strength. To overcome the biological recognition receptors' disadvantages, molecularly imprinted polymers can be used for sensor development. From the point of view of the review, the combination of MIPs and sensors was explained and proposed as an informative paper.

Recent advances in inkjet-printing of advanced materials have provided a versatile platform for the rapid development and prototyping of sensor devices. We have recently demonstrated inkjet-printed surface enhanced Raman scattering (SERS) sensors on flexible substrates for the detection of variety of small molecules [Tay et al. in Front Chem 9:680556 (2021); Tay et al. in J Raman Spectrosc 52:563 (2020)]. These flexible SERS sensors have many advantages for performing point-of-sampling testing, among them liquid or aerosol filtration and swabbing capabilities. These simple sampling and separation features make these inkjet-printed paper-based sensors ideal for field applications. SERS detection of molecules with poor binding affinity towards the plasmonic surfaces of the sensors tends to be inefficient. A surface functionalization approach has been applied to SERS sensors to improve the molecule affinity and hence their detection sensitivity. In this paper, we investigate the optimization of SERS sensor fabrication to achieve optimal performance. Three performance criteria: diffuse reflectance, SERS background intensity from the as-printed blank sensors and SERS performance of sensors exposed to the benzenethiol reporter molecule, are characterized carefully to derive the optimal inkjet-printing conditions for producing the best performing SERS sensors. Additionally, we demonstrate the use of a simple potassium iodide functionalization scheme to improve the detection sensitivity for narcotics such as fentanyl by two orders of magnitude.Graphical abstract