Research group Karsten Haupt
 




Molecular imprinting technology and biomimetic polymers


Index


General principle of molecular imprinting

Imprinting matrices,      General synthesis procedure

Characteristics of imprinted materials,      target molecules

Applications of molecularly imprinted polymers (MIPs)

Our activities in the area








General principle
of molecular imprinting

The technology of molecular imprinting allows for the preparation of synthetic polymers with specific binding sites for a target molecule. This can be achieved if the target is present during the polymerization process, thus acting as a molecular template. Monomers carrying certain functional groups are arranged around the template through either noncovalent or covalent interactions. Following polymerization with a high degree of cross-linking, the functional groups are held in position by the polymer network. Subsequent removal of the template by solvent extraction or chemical cleavage leaves cavities that are complementary to the template in terms of size, shape and arrangement of functional groups. These highly specific receptor sites are capable of rebinding the target molecule with a high specificity, sometimes comparable to that of antibodies. Molecularly imprinted polymers have therefore been dubbed "antibody mimics". It has been shown that they can be substituted for biological receptors in certain formats of immunoassays and biosensors. They have also been used as stationary phases for affinity separations, for the screening of combinatorial libraries, and as enzyme mimics in catalytic applications.
 



Schematic representation of the molecular imprinting process
1: Functional monomers, 2: cross-linker, 3: template molecule; a: assembly of the pre-polymerisation complex, b: polymerisation, c: extraction of the template liberating the binding site

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Imprinting matrices

Organic polymers

    Poly(meth)acrylates and polivinyl polymers synthesised by radical polymerisation (the most common)
    Polyurethane
    Polyaminophenyl boronate
    Poly(phenylene diamine)
    Poly(phenole)
    Overoxidised polypyrrole

Sol-gels

    Silica
    Titanium dioxide



General procedure

For a polymethacrylate MIPs specific for S-propranolol, synthesised by radical polymerisation, one needs the following ingredients :

Ingredient
Cross-linker
Functional monomer(s)
Template
Polymerisation initiator
Porogenic solvent
Example
Ethyleneglycol dimethacrylate
Methacrylic acid
S-propranolol
2,2’-Azobis-iso-
butyronitrile (AIBN)
Toluene
Structure





Typical
amount
(mmol)
40
8
1
0.88  (1 mol-% of number of polymerisable double bonds : here 88 mmol)
1 ... 1.5 x volume of monomers


Oxygen has to be removed by bubbling with nitrogen or argon for 3 min on ice.

Polymerisation can be initiated by heating the mixture to 65 °C, or by UV irradiation at 350 nm.

The different synthesis and processing steps are shown below :                             


procedure




Characteristics of
molecularly imprinted polymers

Physical Stability
Resistant against mechanical stress, high pressures and elevated temperatures
Chemical Stability
Resistant against various organic solvents, against acids and bases depending on the material
Storage Endurance
typically > 1 year at room temperature without loss of performance
Imprint Memory
Repeated use >100 times without loss of memory
Binding Strength
< nM range (best sites)

              
Possible target molecules
   
Works best with small molecules :
Amino acids
Peptides
Steroids
Carbohydrates
Nucleotide bases
Others (pesticides, drugs etc.)
Metal ions
Imprinting of larger structures is more tricky :
Proteins
Cells

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Applications of molecularly imprinted polymers

Antibody / receptor binding site mimics
    Immunoassays
    Drug development / screening

Chemical sensors and biosensors


Tailor-made separation materials

    Enantioseparation and separation of other closely related molecules (HPLC, CEC, TLC etc.)
    Solid-phase extraction for sample preparation

Facilitated synthesis / Catalysis
    Protecting groups
    Equilibrium shifting
    Catalytic polymers (enzyme mimics)

Biomedical
    Slow release matrices
    In-situ or extracorporeal removal of unwanted molecules












Our activities in the area

  Molecularly imprinted stationary phases for separation
        (Enantioselective) membranes
        Solid-phase extraction matrices
        Capillary electrophoresis

  Sensors based on imprinted polymers
        Electrochemical sensors
        Infrared evanescence-wave sensors
        Acoustic sensors (Quartz crystal microbalance)

  Immuno-type binding assays based on imprinted polymers
        Radioassays
        Fluorescence assays
        Enzyme-linked assays (chemiluminescence and colorimetric)
        High-throughput imaging formats
        Flow injection capillary assays
        Homogeneous assays

  Rational design and optimisation of imprinted polymers
 
 

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