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How Reliable Is the Electrochemical Readout of MIP Sensors?

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How Reliable Is the Electrochemical Readout of MIP Sensors? sensors Review How Reliable Is the Electrochemical Readout of MIP Sensors? Aysu Yarman * and Frieder W. Scheller * Institute of Biochemistry and Biology, University of Potsdam, Karl-Liebknecht-Strasse 24-25, 14476 Potsdam, Germany * Correspondence: [email protected] (A.Y.); [email protected] (F.W.S.) Received: 14 April 2020; Accepted: 6 May 2020; Published: 8 May 2020 Abstract: Electrochemical methods offer the simple characterization of the synthesis of molecularly imprinted polymers (MIPs) and the readouts of target binding. The binding of electroinactive analytes can be detected indirectly by their modulating effect on the diffusional permeability of a redox marker through thin MIP films. However, this process generates an overall signal, which may include nonspecific interactions with the nonimprinted surface and adsorption at the electrode surface in addition to (specific) binding to the cavities. Redox-active low-molecular-weight targets and metalloproteins enable a more specific direct quantification of their binding to MIPs by measuring the faradaic current. The in situ characterization of enzymes, MIP-based mimics of redox enzymes or enzyme-labeled targets, is based on the indication of an electroactive product. This approach allows the determination of both the activity of the bio(mimetic) catalyst and of the substrate concentration. Keywords: molecularly imprinted polymers; electropolymerization; direct electron transfer; catalysis; redox marker; gate effect 1. Introduction Over the past decades, increasing attention has been paid to the fast, selective and cost-effective detection and determination of analytes in many areas, including clinical diagnostics, pharmaceutical and environmental analysis, food control and security. Well-established laboratory-based (bio)analytical methods achieved great breakthroughs due to the highly specific interactions involved in most biological processes, e.g., the antigen–antibody interaction, substrate conversion by the action of enzymes and the sequence-specific hybridization of nucleic acids [1]. Nevertheless, biochemical reagents also have some drawbacks, such as stability under harsh conditions (high temperature, organic solvents, limited pH range), reusability and animal usage in preparation (antibodies). Starting from supramolecular chemistry, molecularly imprinted polymers (MIPs) have been created, which potentially overcome these drawbacks [2–8]. They are prepared by polymerizing functional monomers in the presence of a target analyte (template). The subsequent removal of the template from the polymer results in the formation of cavities with a molecular memory mirroring the size and shape of the template (Figure1). MIPs mimic the binding sites of antibodies by substituting the amino acid scaffold for synthetic polymers. Furthermore, catalytically active MIPs containing metal ions or prosthetic groups of oxidoreductases have been developed, which exhibit enzyme-like activity towards substrates [9,10]. The polymer scaffold of the MIP provides specificity by substrate binding to the cavities while the metal complex is the reactive center. The performance of MIPs has also been markedly enhanced by incorporating nanomaterials [11,12] and, as a new trend, by integration in metal organic frameworks (MOFs) [13,14]. Sensors 2020, 20, 2677; doi:10.3390/s20092677 www.mdpi.com/journal/sensors Sensors 2020, 20, 2677 2 of 23 Sensors 2020, 20, x FOR PEER REVIEW 2 of 21 FigureFigure 1. Schematic 1. Schematic representation representation of MIP of preparation. MIP preparation. For aFor good a goodanalytical analytical performance performance of the of sensor the sensor,, the MIP the should MIP should be plac beed placed immediately immediately on the on the surfacesurface of the of electrode. the electrode. Two different Two diff erentprocedures procedures for the for preparation the preparation of MIP of MIPsensors sensors have havebeen been describeddescribed in the in literature the literature [15]. [15]. (i) In(i) the In first the firstprocedure, procedure, the MIP the MIPis separa is separatelytely synthesized synthesized and then and thenimmobilized immobilized on the on the transducertransducer surface. surface. In the In past, the past,MIPs MIPswere weremost mostfrequently frequently synthesized synthesized using using bulk polymerization. bulk polymerization. As a Asresult, a result, monolithicmonolithic materials materials are areproduced, produced, which which are are then then ground ground into smallersmaller particles.particles.The The major majordisadvantage disadvantage of of bulk bulk polymerization polymerization is is the the bad bad accessibility accessibility and and inhomogeneity inhomogeneity of theof the binding bindingpockets, pockets, which which leads leads to ato longera longer template template removal removal time time and and slow slow rebinding. rebinding. To To overcome overcome these theseproblems, problems, didifferentfferentforms formsof ofMIPs, MIPs, suchsuch asas micro-micro- oror nanobeads,nanobeads, nanoparticlesnanoparticles oror nanospheresnanospheres have have beenbeen preparedprepared [[16–19].16–19]. For theFor integration the integration of MIPs of MIPs in inthe the body body of thethe sensor,sensor, di differentfferent methods methods have have been been used used [15,20 ,21]. [15,20,21].The simplest The simplest approach approach is drop is coatingdrop coating [22]. Furthermore,[22]. Furthermore, spin coatingspin coating or spray or spray coating coating have been have appliedbeen applied [23]. Grafting[23]. Grafting is another is another approach approach used forused the for incorporation the incorporation of the MIPsof the [MIPs24]. In [24]. addition In to additionthe describedto the described approaches, approaches, MIPs can MIPs also can be integratedalso be integrated via the preparation via the preparation of composite of composite membranes or membraneslayer-by-layer or layer-by-l assemblyayer [assembly15,20]. [15,20]. (ii) In(ii) the In thesecond second procedure, procedure, the the MIP-based recognitionrecognition layer layer is directlyis directly formed formed on the on transducer. the transducer.In addition In addition to the formation to the offormation an MIP layer of an by self-polymerizationMIP layer by self-polymerization [25] and the microcontact [25] and imprinting the microcontactof a soft polymerimprinting cover of layera soft [26 polymer], electropolymerization cover layer [26], is theelectropolymerization most straightforward is waythe tomost prepare straightforwardMIPs directly way on theto prepare conductive MIPs surface directly of a on transducer, the conductive e.g., on surface an electrode, of a transducer, QCM or SPR e.g., chip on [15 an,20 ,27]. electrode,An advantage QCM or ofSPR electrosynthesis chip [15,20,27]. is thatAn theadvantag film thicknesse of electrosynthesis can be adjusted is bythat varying the film the thickness charge passed can beduring adjusted the polymerization.by varying the Thecharge selection passed of du thering solvent the andpolymerization. supporting electrolyteThe selection and of the the regime solventof potentialand supporting applications electrolyte influence and the morphologythe regime of thepotential polymer applications layer [20,28 ].influence Furthermore, the the morphologyapplication of the of potential polymer pulses layer is[20,28]. a simple Furthermore, method for removingthe application the template of potential after the pulses MIP synthesis.is a simple methodMolecular for removing recognition the bytemplate MIPs has after been the coupledMIP synthesis. in biomimetic sensors with a whole arsenal of Moleculartransducers recognition [20,28–36]. by Among MIPs has them, been electrochemical coupled in biomimetic and optical sensors techniques with clearlya whole dominate arsenal of [31 ,37]. transducersIn addition, [20,28–36]. piezoelectric Among [38 –them,40], thermal electrochemi [41,42]cal and and micromechanical optical techniqu [43,es44 ]clearly transducers dominate have been [31,37].applied In addition, in MIP piezoelectric sensors. All [38–40], steps of thermal MIP synthesis, [41,42] and and micromechanical of the measurement, [43,44] can transducers be analyzed by have methodsbeen applied directly in indicatingMIP sensors. the presenceAll steps of of the MIP target synthesis, molecule and in the of MIP the layer,measurement, or by indirect can methodsbe analyzedevaluating by methods the change directly in the indicating signal of the a marker presence [1,31 of,45 the]. Thetarget direct molecule detection in the of the MIP template layer, or molecules by indirectby themethods redox evaluating conversion the at change an electrode in the [ 46sign], intrinsical of a marker fluorescence [1,31,45]. of The the targetdirect ordetection of a label of [47], the templateRamanand molecules FTIR spectroscopy by the redox [48 ]conversion or surface-enhanced at an electrode infrared [46], absorption intrinsic (SEIRA) fluorescence spectroscopy of the [49] targetspecifically or of a label indicate [47], Raman the presence and FTIR of spectroscopy the template [48] in or the surface-enhanced MIP during the infrared removal absorption and rebinding (SEIRA)ofthe spectroscopy target. In [49] contrast, specific surfaceally indicate plasmon the resonance presence (SPR),of the template quartz crystal in the microbalanceMIP during the (QCM), removaland and capacitor- rebinding or thermistor-based of the target. In sensing contrast, systems surface reflect plasmon specific resonance binding,
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