New Materials in Sensor’s Technology: Fundamentals and Perspectives of Molecular Imprinting in Sensor Applications Dr. Ayman H. Kamel Associate Prof. of Analytical Chemistry Faculty of Science, Ain Shams University ahkamel76@sci.asu.edu.eg

1. Introduction Molecular imprinting is one of the most promising approaches to achieve precise molecular recognition. The goal of molecular imprinting is to organize the polymeric matrix around template molecules in such a manner as to create voids, pockets, or cavities, which, after removal of the template, persist and are able to rebind template or target .

5. π-π Interactions and electrostatic effects. The affinity of rebinding will depend on the strength of the intermolecular forces between the template and polymer. These forces include: 1. Hydrogen Bonding. 2. Metal coordination. 3. hydrophobic forces. 4. Van der Waals forces. 5. π-π Interactions and electrostatic effects. Some of all of these forces contribute to target binding in all imprinted polymers. The affini

Optimization of MIP Formulation Factors affect the final characteristics of the obtained materials in terms of capacity, affinity, and selectivity for the target analyte: Amount and nature of monomer Cross-linker Progenic solvent High ratios of functional monomer to template result in a high nonspecific affinity. Low ratios produce fewer complexations due to insufficient functional groups

The process of producing a molecular-sensing polymer includes the following steps: Choice and preparation of proper agents (monomer, cross-linker, porogen) Synthesis of the cross-linked copolymers. Washing of the polymers for removing the template. Optimizing of the polymer for molecular selectivity. Use of the polymers in the construction of MIP-based membrane sensors.

2. Synthesis of MIPs Three steps are used to prepare molecularly imprinted polymers: mixing template and monomers. Polymerization. Template removal.

2.1. Traditional bulk Polymerization The most common method of preparing MIPs is bulk polymerization, in which all components are polymerized in a mold. Functional monomers and a high concentration of cross-linker are typically polymerized in the presence of the template molecules. Subsequent removal of templates from the polymeric matrix leaves behind binding sites that are complementary to the size, shape, and functionality of template molecules

Formation of pre-polymerization complex The print molecule is dissolved in the acetonitrile porogen together with the two different functional monomers. Formation of pre-polymerization complex The template molecules are removed from the polymer. The space in the polymer originally occupied by the template molecule is left as a cavity grinding and sieving, resulting in particles with an average size of 10-25 µm. The polymerization is subsequently initiated by raising the temperature to 60°C

Drawbacks of this method It produces deeply embedded binding sites and suffer from some drawbacks, such as: Slow mass transfer. Moderate sensitivity and selectivity. Incomplete template removal, and broad guest affinity.

2.2. Precipitation/dispersion Polymerisation The technique involves the polymerisation of monomers under diluted conditions, typically below 5% w/v (monomers/solvent). Therefore, it requires the selection of monomers that can form sufficiently strong binding interactions with the template under such conditions. The beads prepared by this approach show higher binding capacity than the corresponding bulk polymers, due to their higher surface to volume ratio. The quality of the binding sites is not affected by polymer grinding.

2.3.Suspension Polymerization In this approach, polymerizable droplets, which can be stabilized using a surfactant, are suspended inside an immiscible phase and polymerization takes place inside the droplets. As in suspension polymerization, the monomer phase is dispersed inside a continuous phase of a monomer immiscible solvent, usually water. However in this approach, the monomer droplets are enclosed inside micelles along the continuous phase and stabilized with a surfactant. The method can be easily scaled up and does not require the use of organic solvents. The main drawbacks include the possible interference of water or the surfactant during the imprinting process. 2.4. Emulsion Polymerization

Schematic representation of the surface semicovalent imprinting approach by mini-emulsion polymerization.

2.5. The Sol-gel Technique Sol-gel MIP materials are inorganic (siloxane) based polymer matrix produced by an acid or base catalyzed hydrolysis and condensation of a series of silane monomers with excellent physical rigidity, chemical inertness, and thermal stability properties. Sol-gel imprinting has drawn growing interest in molecular imprinting in polymer matrices that may prompt the tailoring of unique MIP materials with controllable pore size, structural rigidity, thermal stability, and enhanced recognition performs.

Schematic illustration for the molecular imprinting mechanism of TNT in a silica matrix through the anione-cation pair and gelation

Therefore, this process is able to entrap a variety of organic, organometallic, and biological molecules (microorganisms, antibodies, DNA, proteins, and enzymes) within meso/microporous polymeric matrix. Such a method suffers from several challenges, such as slow diffusion kinetics, long response time, and low sensitivity.

2.6. Electro-assisted Deposition One of the outstanding advantages of electro-assisted deposition is that there is no need to remove the template by the extraction process, because the integration of MIPs with sensors can be easily obtained through in situ polymerization, by either grafting with chemical or UV initiation or by photochemical or thermal initiation.

3. Characterization of Molecularly Imprinted Polymers FTIR Scanning electron microscopy (SEM) is employed to determine the shape and surface morphology of the produced polymer particles Photon correlation spectroscopy for measuring the particle size and size distribution of polymer particles The Brunauere Emmette Teller (BET) method for measuring the specific surface area, pore volume, and average pore diameter of polymer particles. Batch Rebinding Experiments to assess the existence of specific cavities designed for the target analytes

4. MIP-Based Potentiometric Sensors The immobilization of MIPs on the transducer surface is an important feature in the design of MIP-based potentiometric sensors 4.1. Plasticized PVC Membrane Sensors Entrapment of MIP particles into PVC membranes

Ayman H. Kamel, Tamer Y. Soror, Fahad M. Al Romian, Anal Ayman H. Kamel, Tamer Y. Soror, Fahad M. Al Romian, Anal. Methods, 2012, 4, 3007

4.2. Self-Assembled Monolayer-Based Sensors This technique was applied for detection of globular proteins such as myoglobin and hemoglobin with parts per million accuracy Self-Assembled Monolayer-Based Sensors

4.3. Sensor Based on In-Situ Polymerization is the best immobilization procedure and consists of in-situ synthesis of MIPs at the transducer surface

4.4. Sensor Based on ITO Thin Film A potentiometric chemosensor for determination of dipicolinic acid (2,6-pyridinedicarboxylic acid, DPA) was developed based on the surface imprinting technique coupled with a nanoscale transducer, an indium tin oxide (ITO)-coated glass plate by Y. Zhou Y. Zhou et al. / Biosensors and Bioelectronics 20 (2005) 1851–1855

4.5. Sensors Based on Ion-Selective Field-Effect Transistor semiconductor devices that respond to the surface electric gradient or charge at the gate electrode. A chemical reaction at the surface of the silicon chip will shift the surface potential and hence affects the current, which allows the rate of the reaction to be monitored.

4.6. Chemically Modified Carbon Paste Electrodes The CMCPEs can be prepared by thoroughly mixing graphite powder, paraffin oil, and MIP particles S. Javanbakht, A. Eynollahi Fard, M. Mohammadi, M.R. Abdouss, P. Ganjali, L. Norouzi Safaraliee, Anal. Chim. Acta 612 (2008) 65.

5. MIP-BASED SENSORS FOR DRUGS DETERMINATION IN BIOLOGICAL AND PHARMACEUTICAL SAMPLES Ayman H. Kamel, W. H. Mahmoud, M. S. Mostafa, Anal. Methods, 2011, 3, 957

6. MIP-BASED SENSORS FOR THE DETERMINATION OF POLLUTANTS IN THE ENVIRONMENTAL SAMPLES Man-tailored biomimetic sensors of molecularly imprinted polymers for selective recognition of some phenylurea herbicides and their application to potentiometric transduction Ayman H. Kamel and F. M. Al Romian, Int. J. Chem. Mater. Sci. Vol. 1(1), pp. 001-012, 2013

Future outlook Development of sensor technology is the need for mass-produced and low cost disposable transducers . This will be relevant for environmental and biomedical analysis. screen printed electrodes fulfill this need. A significant trend in the sensor field goes toward miniaturization and the development of multi sensor arrays. electronic tongues fulfill this need. Molecular imprinting is multidisciplinary in nature and possesses a high potential for applications in particular through their capacity for serving as robust artificial receptors. I am confident that in the future there will be a large number of different systems and companies using this exciting new general platform technology, encompassing the analytical area including solid phase extraction, biosensor mimics, separation.