1. 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

2. 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 .

4. 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

5. 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

6. 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.

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

8. 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

9. 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 µm.
The polymerization is subsequently initiated by raising the temperature to 60°C

10. 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.

11. 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.

12. 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

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

14. 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.

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

16. 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.

17. 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.

19. 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

20. 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

21. 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

22. 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

23. 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

24. 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

25. 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.

26. 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.

27. 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

31. 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 , 2013

36. 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.