A Long History of Molecular Imprinting: Background


Molecular imprinting is a powerful technique used to create polymeric materials with biomimetic recognition sites that mimic biological receptors. 
This polymeric structure is formed through template-assisted synthesis, where functional monomers are co-polymerized in the presence of a template—either the entire target molecule or a portion of it—along with potential crosslinkers and initiators. Once polymerization is complete, the template molecule is extracted, leaving behind binding cavities in the polymer network. 

These cavities are complementary in shape, structure, and functional group arrangement to the template molecule, functioning like a “lock and key” mechanism to selectively re-bind the target molecule, mimicking the biological antibody-antigen affinity.

Advantages and Applications

Due to continuous advancements in material science, Molecularly Imprinted Polymers (MIPs) now rival their natural counterparts in molecular recognition assays. MIPs are cost-effective, easy to produce, and exhibit remarkable chemical and thermal stability (e.g., solvent tolerance, extreme pH resistance, and the ability to undergo sterilization). They maintain their integrity during storage under non-controlled environmental conditions and offer morphological flexibility (films or nanostructures) as well as compatibility with electronic integration. Additionally, MIPs possess numerous biomimetic functions beyond molecular recognition, such as catalytic activity and stimuli-responsive behaviors.

Historical Development

The concept of MIPs originated around 1940, inspired by L. Pauling’s theory on in vitro antibody production using template molecules. However, significant progress in MIPs began in the 1970s with two pivotal works by Wulff and Mosbach. Wulff introduced a covalent imprinting method, while Mosbach described a non-covalent approach. The number of research articles on MIPs has surged since 2013, with over 10,000 papers published by 2022, according to a bibliometric analysis using the Scopus database (1999-2022).

Diverse Applications

Molecular imprinting has captivated the scientific community, diversifying greatly in materials, template types, and applications. MIPs are versatile tools in various research fields, including biosensing, separation science, biomedical diagnostics, environmental monitoring, pharmaceutical screening, drug delivery, and tissue engineering.

Healthcare Applications


In healthcare, MIPs address both diagnostic and therapeutic challenges. For in vitro diagnostics, MIPs are utilized to detect and quantify biomarkers linked to biological or (patho-) physiological states. They are ideal for diagnostic assays on solid supports, in solutions, or for pre-analytical applications like protein enrichment or interference removal from complex biological samples (e.g., blood, plasma, serum). Moreover, efforts are ongoing to design MIPs with in vivo therapeutic properties, a primary objective in the fast-growing field of nanomedicine. These nano-MIPs, often in the form of spherical nanoparticles, function as immune checkpoint inhibitors or drug delivery systems targeting specific pathological sites, such as cancer cells.

Performance Evaluation

The integration of diagnostic and therapeutic properties within a single MIP formulation, known as theranostics, is a burgeoning area of research. The general synthetic receptor-analyte recognition mechanism is expressed by a reversible affinity reaction: [MIP] + [A] ↔ [MIPA], where [MIP] is the concentration of surface MIP binding sites, [A] is the concentration of the free analyte, and [MIPA] is the complex concentration. To assess the performance of MIPs in analyte recognition, three main parameters are evaluated:
  • Binding Affinity: Expressed as the dissociation equilibrium constant, 𝐾D (mol L^-1) = [MIP][A]/[MIPA], where a lower 𝐾D indicates stronger binding.
  • Specificity: The MIP’s ability to bind only the target analyte without interference from other molecules.
  • Imprinting Factor (IF): The ratio of analyte binding to MIP versus non-imprinted polymer (NIP) under identical conditions (IF = MIP/NIP).
The NIP surface is synthesized similarly to MIPs but without the template molecule.

Future Directions

The following sections will briefly discuss the rationale behind MIPs and the various imprinting strategies used for their preparation, aimed at both in vitro and in vivo applications.
Previous Post Next Post