Molecularly imprinted polymers (MIPs)
What are MIPs?
MIPs are engineered cross-linked polymers that can exhibit high affinity and selectivity towards a single compound or they can be designed to exhibit ‘Class Selectivity’ for a family of related compounds. MIPs are able to bind analytes even when these are present in complex matrices (eg plasma, urine, muscle tissue, food matrices, environmental samples, process solutions etc). An important strength of MIPs is that they are able to bind to trace levels of the target analyte, in the presence of large excess of other compounds that have similar physico-chemical properties.
How do they behave?
Binding
Unlike most separation particles that exhibit only non-selective interactions, MIP particles have a selective synthetic recognition site (or imprint), which is sterically and chemically complementary to a particular analyte or class of analytes. The interactions mimic antibody or receptor binding and are stronger than interactions obtained with conventional separation materials.
Economics and Stability
MIPs are economical and fast to produce and are robust and stable under storage. They can be used at elevated temperatures, in organic solvents and at extreme pH values. They also display a higher sample load capacity than is typical for immunoaffinity based sorbents. This results in higher recoveries for analytical applications and suitability of using the sorbents for semi-preparative or preparative scale separations.
Material design
In trace analysis applications, the level of compounds that may leach out from the MIP are extremely low, due to efficient washing procedures and do not interfere with the quantification of the target analyte. Template molecules used are usually analogs that differ sufficiently from the target analytes to avoid co-elution problems. Typically, any leachable compound from the MIP preparation is removed (around 99 %) and is normally not detected during analysis.
MIP Technologies has extensive experience in designing the polymer components, that include specialized monomers and optimized templates which may be isosteric or isoelectronic analogues of the desired analytes. Our ‘Rule of six’ for analytical applications has been developed after many years of experience (see below).
The analyte
MIPs can be routinely prepared for a variety of low-molecular weight compounds, with molecular weights up to about 3000 Da. Larger target analytes can also be targeted, such as peptides, carbohydrates and proteins by making use of accessible epitopes.
The MIP ‘Rule of six’
- Never use the analyte as a template unless there is absolutely no alternative
- Make rational choices about which regions of an analyte are likely to command the best types of interaction in a low dielectric medium (organic solvent) and then incorporate these elements in an analog of the analyte molecule
- Select monomers that are likely to form strong interactions in the chosen solvent (e.g., Brönsted acids or bases/H-donors or acceptors/nonpolar groups, etc.) - this will increase capacity and influence homogeneity of the binding cavities
- Choose templates and monomers that will be soluble in the porogenic solvent to be used in the polymerization - this may seem obvious but it sometimes requires carrying out solubility tests
- Ensure as far as possible that the template-monomer mixture is stable and does not undergo side reactions under the polymerization conditions
- Consider the nature of the matrix from which the analyte will eventually be extracted when selecting the cross-linking monomer - a range of di- or tri-unsaturated cross-linking monomers (e.g., vinylic, acrylic, methacrylic, acrylamide, etc.) with varying chemistries are available to create the porous organic network material.
