Artificial Recognition Element Research Articles

Cupric ion coordination-mediated molecularly imprinted electrochemical sensor for the recognition and ratiometric detection of lidocaine

Molecularly imprinted polymers (MIPs) have been widely used as artificial recognition elements in sensing applications. However, their electrochemical sensing performance is generally hampered by limited affinity and uncontrolled condition change. In this work, a novel MIP electrochemical sensor based on metal coordination interaction was prepared and used for the recognition and ratiometric detection of lidocaine (LC). The sensor was constructed by electrodepositing Cu-coordinated MIP on biomass carbon modified glassy carbon electrode. Herein, Cu2+ ions acted as anchor for the immobilization of LC during the synthesis process, enabling the orderly formation of molecular recognition sites. Reversely, the metal coordination between Cu2+ ions and LC molecules facilitated the recognition of LC. Moreover, the doped cupric ions in the polymer film could provide a reference signal for subsequent ratiometric strategy. Thus the resulting sensor exhibited high selectivity, sensitivity, satisfactory reproducibility, and anti-interference ability. Under the selected conditions, the peak current ratio of LC and cupric ion was linear to LC concentration in the range of 0.008–2.5 μmol L−1 (R2 = 0.9951), and the limit of detection was 1.9 nmol L−1 (S/N = 3). The practical feasibility of the sensor was evaluated by detecting human serum and pharmaceutical samples, and satisfactory outcomes were obtained.

Carbon felt tailored with artificial recognition elements: an effective membrane for bisphenol A adsorption and removal

Carbon felt tailored with artificial recognition elements: an effective membrane for bisphenol A adsorption and removal

A ratiometric electrochemical sensing platform based on multifunctional molecularly imprinted polymer with catalytic activity for the detection of psychoactive substances

Molecularly imprinted polymers (MIPs) are widely used as artificial recognition element in sensing field, but their electrochemical sensing performances are generally affected by their poor catalytic activity and unruly condition change. In this work, an MIP film with catalysis (Fe-DMMIP) is constructed by electrodeposition of Fe-coordinated aminophenanthroline and 3,4-ethylenedioxythiophene on N, S doped C material, using cannabinoid (CBD) as template molecule. Due to the presence of Fe–N active sites, the obtained Fe-DMMIP possesses enzyme-like catalytic activity besides conventional recognition capability. Accordingly, the sensor exhibits high electrocatalytic activity and selectivity. Moreover, the Fe-DMMIP can produce a stable and well-defined signal as an internal reference around 0 V (vs. Ag/AgCl) for ratiometric sensing. Under the optimal conditions, the ratiometric signal is linear to CBD concentration in the range of 0.004–0.8 μmol L−1 (R2 = 0.9946) with a detection limit of 2.9 nmol L−1. The ratiometric sensor shows high reproducibility, stability and applicability. In addition, through replacing the template molecule, the resulting biomimetic sensor also exhibits good performance in sensing other psychoactive substances such as melatonin and 5-hydroxytryptophan, with LODs of 19 nmol L−1 and 8 nmol L−1for them, respectively. Therefore, the developed sensing platform has good prospects, and this work provides a new way for developing ratiometric electrochemical sensors with high sensitivity, reproducibility and anti-interference ability.

Advances in fabrication of molecularly imprinted electrochemical sensors for detection of contaminants and toxicants

Worldwide growing concerns about water contamination and pollution have increased significant interest in trace level sensing of variety of contaminants. Thus, there is demand for fabrication of low cost, miniaturized sensing device for in-situ detection of contaminants from the complex environmental matrices capable of providing selective and sensitive detection. Molecularly imprinted polymers (MIPs) has portrayed a substantial potential for selective recognition of various toxicants from a variety of environmental matrices, thus widely used as artificial recognition element in the electrochemical sensors (ECS) owing to their chemical stability, easy and low cost synthesis. The combination of nanomaterials modifiers with MIPs has endowed MIP-ECS with significantly improved sensing performance in the recent years, as the nanomaterial provide properties such as increased surface area, increased conductivity and electrocatalytic activity with enhanced electron transport phenomena, whereas MIPs provide selective recognition effect.In the present review, we have summarized the advances of MIP-ECS electrochemical sensors reported in last six years (2017–2022) for sensing of variety of contaminates including drugs, metal ions, hormones and emerging contaminates. Scope of computational modelling in design of sensitive and selective MIP-ECS is reviewed. We have focused particularly on the synthetic protocols for MIPs preparation including bulk, precipitation, electropolymerization, sol-gel and magnetic MIPs. Moreover, use of various nanomaterial as modifiers and sensitizers and their effects on the sensing performance of resulting MIP-ECS is described. Finally, the potential challenges and future prospects in the research area of MIP-ECS have been discussed.

Recent Advances in Quartz Crystal Microbalance Biosensors Based on the Molecular Imprinting Technique for Disease-Related Biomarkers

The molecular imprinting technique is a quickly developing field of interest regarding the synthesis of artificial recognition elements that enable the specific determination of target molecule/analyte from a matrix. Recently, these smart materials can be successfully applied to biomolecule detection in biomimetic biosensors. These biosensors contain a biorecognition element (a bioreceptor) and a transducer, like their biosensor analogs. Here, the basic difference is that molecular imprinting-based biosensors use a synthetic recognition element. Molecular imprinting polymers used as the artificial recognition elements in biosensor platforms are complementary in shape, size, specific binding sites, and functionality to their template analytes. Recent progress in biomolecular recognition has supplied extra diagnostic and treatment methods for various diseases. Cost-effective, more robust, and high-throughput assays are needed for monitoring biomarkers in clinical settings. Quartz crystal microbalance (QCM) biosensors are promising tools for the real-time and quick detection of biomolecules in the past two decades A quick, simple-to-use, and cheap biomarkers detection technology based on biosensors has been developed. This critical review presents current applications in molecular imprinting-based quartz crystal microbalance biosensors for the quantification of biomarkers for disease monitoring and diagnostic results.

An ultrasensitive molecularly imprinted polymer-based electrochemical sensor for the determination of SARS-CoV-2-RBD by using macroporous gold screen-printed electrode

Herein, a novel molecularly imprinted polymer (MIP) based electrochemical sensor for the determination of the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2-RBD) has been developed. For this purpose, first, a macroporous gold screen-printed electrode (MP-Au-SPE) has been fabricated. The MIP was then synthesized on the surface of the MP-Au-SPE through the electro-polymerization of ortho-phenylenediamine in the presence of SARS-CoV-2-RBD molecules as matrix polymer, and template molecules, respectively. During the fabrication process, the SARS-CoV-2-RBD molecules were embedded in the polymer matrix. Subsequently, the template molecules were removed from the electrode by using alkaline ethanol. The template molecules removal was studied using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDX), and attenuated total reflectance spectroscopy (ATR). The fabricated MIP film acted as an artificial recognition element for the measurement of SARS-CoV-2-RBD. The EIS technique was used for the measurement of the SARS-CoV-2-RBD in the saliva solution. The electron transfer resistance (Ret) of the MIP-based sensor in a ferri/ferrocyanide solution increased as the SARS-CoV-2-RBD concentration increased due to the occupation of the imprinted cavities by the SARS-CoV-2-RBD. The MIP-based sensor exhibited a good response to the SARS-CoV-2-RBD in the concentration range between 2.0 and 40.0 pg mL-1 with a limit of detection of 0.7 pg mL-1. The obtained results showed that the fabricated MIP sensor has high selectivity sensitivity, and stability.

A Novel Thermal Analysis Method for the Detection of a Range of Biomedical Targets

Introduction There are a number of challenges in improving the diagnostic process in the healthcare industry. Least of which is finding ways to quickly and accurately test for particular compounds associated with different diseases and conditions. Traditional methods for detecting the presence of these compounds are both time consuming and costly. This is especially restricting in countries without well-equipped or maintained laboratories [1]. Having a method that provides quick, low-cost and reliable screening would save thousands of dollars annually and allow for quicker diagnoses. A detection method that satisfies these criteria is the Heat-Transfer Method (HTM), where changes in thermal resistance can be monitored in real-time to determine the presence of specific analytes [2]. This talk will discuss three classes of biomedical analytes (cardiac biomarkers, bacteria, and antibiotic drugs) that were studied using thermal detection, and will highlight artificial recognition elements we have developed and implemented in our sensors. Each analyte poses a unique challenge in terms of recognition and detection as they encompass a range of shapes, sizes and chemistry. Methods Two different cardiac biomarkers were studied using imprinted nanoparticles (nanoMIPs) specifically designed to have high binding affinity to the individual proteins [3]. The nanoparticles were subsequently deposited onto multiple thermocouples via dipcoating and the thermocouples were then inserted into a custom flow cell. To examine the use of thermal detection for bacteria, the growth of a model organism, Staphylococcus aureus, was monitored [4]. This was done in both buffered solutions and wastewater samples to determine the effect a complex medium has on the measurements. In combination with these measurements, imprinted polymers were developed for S. aureus using photopolymerization. The final analytes examined were beta-lactam antibiotic drugs, including nafcillin and amoxicillin. Imprinted polymers were used as the receptor for the sensor with their binding capabilities compared on various substrates. Polymers for each drug were generated in two different ways: microparticles formed after bulk polymerization, and thin films via photopolymerization. Both were deposited onto screen-printed electrodes and the thin films were also deposited onto borosilicate glass. Results and Conclusions The nanoMIPs showed comparable affinity to the biomarker proteins as commercial antibodies, and the multiplex design for the thermocouples allowed for detection in the 4-8 ng/mL range, well within the range of physiologically relevant concentrations. Optimization of the flow cell with the multiplexed array was conducted, showing that the positioning of the thermocouples with respect to the flow through the chamber will influence the measurement. When examining the behaviour of bacteria, a change in thermal resistance was measured as the bacterial colony grew even in the complex digestate solutions. Specific changes in their morphology were detected at higher temperatures, as determined by SEM and resistance changes. SEM images showed the presence of S. aureus binding sites in the imprinted polymer as well as partial rebinding after the introduction of a bacteria-containing solution. For the antibiotics, the thermal resistance increased upon target binding for both microparticles and thin films, which was translated to a LOD of 1.89 ± 1.03 and 0.54 ± 0.1 nM, respectively. Changes to the polymer films were then investigated, including a change in substrate and the introduction of a fluorescent moiety. Overall, these results show how versatile thermal detection can be in terms of sensor design while still providing fast, accurate, and easy-to-read results. In combination with low-cost detection elements, they could provide an avenue to accessible diagnostic tools for less developed areas. [1] Kimani, F. W.; Mwangi, S. M.; Kwasa, B. J.; Kusow, A. M.; Ngugi, B. K.; Chen, J.; Liu, X.; Cademartiri, R.; Thuo, M. M. Rethinking the Design of Low-Cost Point-of-Care Diagnostic Devices. Micromachines 2017, 8 (11), 317.[2] Eersels, K.; van Grinsven, B.; Peeters, M.; Cleij, T. J.; Wagner, P. Heat Transfer as a New Sensing Technique for the Label-Free Detection of Biomolecules. In Label-Free Biosensing: Advanced Materials, Devices and Applications; Schöning, M. J., Poghossian, A., Eds.; Springer International Publishing, 2018; 383–407.[3] Crapnell, R. D.; Canfarotta, F.; Czulak, J.; Johnson, R.; Betlem, K.; Mecozzi, F.; Down, M. P.; Eersels, K.; van Grinsven, B.; Cleij, T. J.; Law, R.; Banks, C. E.; Peeters, M. Thermal Detection of Cardiac Biomarkers Heart-Fatty Acid Binding Protein and ST2 Using a Molecularly Imprinted Nanoparticle-Based Multiplex Sensor Platform. ACS Sensors 2019, 4 (10), 2838–2845.[4] Betlem, K.; Kaur, A.; Hudson, A. D.; Crapnell, R. D.; Hurst, G.; Singla, P.; Zubko, M.; Tedesco, S.; Banks, C. E.; Whitehead, K.; Peeters, M. Heat-Transfer Method: A Thermal Analysis Technique for the Real-Time Monitoring of Staphylococcus Aureus Growth in Buffered Solutions and Digestate Samples. ACS Appl. Bio Mater. 2019, 2 (9), 3790–3798. Figure 1

Evaluation of Molecularly Imprinted Polymers for Point-of-Care Testing for Cardiovascular Disease.

Molecular imprinting is a rapidly growing area of interest involving the synthesis of artificial recognition elements that enable the separation of analyte from a sample matrix and its determination. Traditionally, this approach can be successfully applied to small analyte (<1.5 kDa) separation/ extraction, but, more recently it is finding utility in biomimetic sensors. These sensors consist of a recognition element and a transducer similar to their biosensor counterparts, however, the fundamental distinction is that biomimetic sensors employ an artificial recognition element. Molecularly imprinted polymers (MIPs) employed as the recognition elements in biomimetic sensors contain binding sites complementary in shape and functionality to their target analyte. Despite the growing interest in molecularly imprinting techniques, the commercial adoption of this technology is yet to be widely realised for blood sample analysis. This review aims to assess the applicability of this technology for the point-of-care testing (POCT) of cardiovascular disease-related biomarkers. More specifically, molecular imprinting is critically evaluated with respect to the detection of cardiac biomarkers indicative of acute coronary syndrome (ACS), such as the cardiac troponins (cTns). The challenges associated with the synthesis of MIPs for protein detection are outlined, in addition to enhancement techniques that ultimately improve the analytical performance of biomimetic sensors. The mechanism of detection employed to convert the analyte concentration into a measurable signal in biomimetic sensors will be discussed. Furthermore, the analytical performance of these sensors will be compared with biosensors and their potential implementation within clinical settings will be considered. In addition, the most suitable application of these sensors for cardiovascular assessment will be presented.

Cell Therapies for Parkinson's Disease.

Cell Therapies for Parkinson's Disease.

Heparin molecularly imprinted polymer thin flm on gold electrode by plasma-induced graft polymerization for label-free biosensor

Heparin, a highly sulfated glycosaminoglycan, is an important biomaterial having biological and therapeutic functionalities such as anticoagulation, regeneration, and protein stabilization. This study addresses a label-free quartz crystal microbalance (QCM) biosensor for heparin detection based on a macromolecularly imprinted polymer (MIP) as an artificial recognition element. We demonstrate the novel strategy for MIP in the form of thin film on a gold (Au) electrode with the plasma-induced graft polymerization (PIP) technique. The procedure of PIP is as follows: (i) Hexamethyldisiloxane plasma-polymerized thin film (PPF) as a pre-coating scaffold of active species for PIP (post-polymerization) is deposited on an Au electrode. (ii) The PPF/Au electrode is soaked in an water solution containing heparin (template), (2-(methacryloxy)-ethyl)trimethylammonium chloride acrylamide (functional monomer), acrylamide, and N,N-methylenebisacrylamide (crosslinker). Double bonds of monomer and crosslinker attacked by residually active species in pre-coating PPF cause radical chain reaction. Consequently, a growing polymer network of 20 nm thickness of PIP-MIP thin film is formed and grafted on the PPF/Au surface. (iii) The PIP-MIP/PPF/Au is washed by sodium chloride solution so as to remove the template. Non-imprinted polymer (NIP) is carried out like the same procedure without a template. The AFM, XPS, and QCM measurements show that the PIP process facilitates macromolecularly surface imprinting of template heparin where the template is easily removed and is rapidly rebound to PIP-MIP without a diffusional barrier. The heparin-PIP-MIP specifically binds to heparin compared with heparin analog chondroitin sulfate C (selective factor: 4.0) and a detectable range of heparin in the presence of CS (0.1 wt%) was 0.001-0.1 wt%. The PIP-NIP does not show selectivity between them. The evaluated binding kinetics are association (ka = 350 ± 100 M−1 s−1), dissociation (kd = (5.0 ± 2.0) × 10−4 s−1), and binding (KD = 1.3 ± 0.6 μM) constants, demonstrating that the PIP-MIP as a synthetic antibody can be applied to analytical chemistry.

Transferrin-navigation Nano Artificial Antibody Fluorescence Recognition of Circulating Tumor Cells

Specific recognition of circulating tumor cells (CTCs) is of great significance for cancer diagnosis and personalized therapy. The antibodies and aptamer are commonly used for recognition of CTCs, but they often suffer from low stability and high cost. Therefore, chemically stable and low-cost artificial recognition elements are still highly demanded. Herein, we prepared nano artificial antibody based on molecular imprinting and applied for fluorescence recognition of CTCs. Surface imprinting was employed to construct a transferrin (TRA)-imprinted layer on the surface of rhodamine doped silica nanoparticles. Take advantage of the specific interaction between TRA and TRA receptor (overexpressed on cancer cells), the as-prepared TRA-imprinted artificial antibody was allowed for specific targeting cancer cells mediated by TRA. And the average recognition efficiency of the artificial antibody for the cancer cells was 88% through flow cytometry. Finally, the nano artificial antibody was successfully applied to specific identify mimetic CTCs, under the same conditions, the recognition ability of artificial antibody for CTCs was 8 times higher than the white blood cells.

Enzyme-linked immunoassay based on imprinted microspheres for the detection of sulfamethazine residue

This study attempts to develop an enzyme-linked immunoassay (ELISA) using a molecularly imprinted polymer (MIP) as an artificial recognition element. The MIP microspheres were prepared using precipitation polymerization with SM2 as the template molecule, methacrylic acid as the functional monomer and ethylene glycol dimethacrylate as the cross-linker. After the microspheres were coated in microtiter plate wells, the molecular imprinting ELISA (MI-ELISA) method was established based on the direct competition between free SM2 and horseradish peroxidase (HRP)-labelled SM2 in heterogeneous mode. The linear regression analysis data for the calibration curve showed a good linear relationship with a regression coefficient of 0.999 in the concentration range of 100μgL−1–3200μgL−1. Furthermore, following the selective solid-phase extraction (SPE) with bulk SM2 MIPs as the sorbent and MI-ELISA detection, the limits of detection and quantification were 6.8μgkg−1 and 20.4μgkg−1, respectively, for SM2 in swine muscle. For the first time, MI-ELISA combined with molecular imprinting SPE was developed to determine trace SM2 in real samples, and the results show that it can be a useful analytical tool for quick detection in residue analysis.

Imprinting of Microorganisms for Biosensor Applications.

There is a growing need for selective recognition of microorganisms in complex samples due to the rapidly emerging importance of detecting them in various matrices. Most of the conventional methods used to identify microorganisms are time-consuming, laborious and expensive. In recent years, many efforts have been put forth to develop alternative methods for the detection of microorganisms. These methods include use of various components such as silica nanoparticles, microfluidics, liquid crystals, carbon nanotubes which could be integrated with sensor technology in order to detect microorganisms. In many of these publications antibodies were used as recognition elements by means of specific interactions between the target cell and the binding site of the antibody for the purpose of cell recognition and detection. Even though natural antibodies have high selectivity and sensitivity, they have limited stability and tend to denature in conditions outside the physiological range. Among different approaches, biomimetic materials having superior properties have been used in creating artificial systems. Molecular imprinting is a well suited technique serving the purpose to develop highly selective sensing devices. Molecularly imprinted polymers defined as artificial recognition elements are of growing interest for applications in several sectors of life science involving the investigations on detecting molecules of specific interest. These polymers have attractive properties such as high bio-recognition capability, mechanical and chemical stability, easy preparation and low cost which make them superior over natural recognition reagents. This review summarizes the recent advances in the detection and quantification of microorganisms by emphasizing the molecular imprinting technology and its applications in the development of sensor strategies.

PEGylated Artificial Antibodies: Plasmonic Biosensors with Improved Selectivity.

Molecular imprinting, which involves the formation of artificial recognition elements or cavities with complementary shape and chemical functionality to the target species, is a powerful method to overcome a number of limitations associated with natural antibodies. An important but often overlooked consideration in the design of artificial biorecognition elements based on molecular imprinting is the nonspecific binding of interfering species to noncavity regions of the imprinted polymer. Here, we demonstrate a universal method, namely, PEGylation of the noncavity regions of the imprinted polymer, to minimize the nonspecific binding and significantly enhance the selectivity of the molecular imprinted polymer for the target biomolecules. The nonspecific binding, as quantified by the localized surface plasmon resonance shift of imprinted plasmonic nanorattles upon exposure to common interfering proteins, was found to be more than 10 times lower compared to the non-PEGylated counterparts. The method demonstrated here can be broadly applied to a wide variety of functional monomers employed for molecular imprinting. The significantly higher selectivity of PEGylated molecular imprints takes biosensors based on these artificial biorecognition elements closer to real-world applications.

Biomimetic Sensor Potentiometric System for Doxycycline Antibiotic Using a Molecularly Imprinted Polymer as an Artificial Recognition Element

Biomimetic Sensor Potentiometric System for Doxycycline Antibiotic Using a Molecularly Imprinted Polymer as an Artificial Recognition Element

The study of oxidization fluorescence sensor with molecular imprinting polymer and its application for 6-mercaptopurine (6-MP) determination

This paper developed optical fiber sensor based on molecular imprinted polymer as artificial recognition element for the determination of 6-mercaptopurine (6-MP) in human serum. This approach displayed high sensitivity by oxidizing 6-MP to a strong fluorescent compound with H 2O 2 in the alkaline media. It offered a relatively nice selectivity for 6-MP detection by molecular imprinted polymer's recognition. The relative standard deviation (R.S.D.) was 5% for a same sensor ( n = 5) when 6-MP concentration was 1.0 × 10 −7 g mL −1 in serum. The developed method was satisfactorily applied to the determination of 6-MP in human serum without any necessity for sample treatment or time-consuming extraction steps prior to the analysis.

Assay System for the Herbicide 2,4-Dichlorophenoxyacetic Acid Using a Molecularly Imprinted Polymer as an Artificial Recognition Element

Noncovalent molecular imprinting of a synthetic polymer with the herbicide 2,4-dichlorophenoxyacetic acid has been achieved in the presence of the polar solvents methanol and water. Formation of the prearranged complex relied on hydrophobic and ionic interactions between the template and the functional monomer 4-vinylpyridine. The polymer obtained binds the original template with an appreciable selectivity over structurally related compounds. The potential use of micrometer-sized imprinted polymer particles as the recognition element in a radioligand binding assay for 2,4-dichlorophenoxyacetic acid is demonstrated.