Towards water compatible MIPs for sensing in aqueous media

When synthesizing molecularly imprinted polymers (MIPs), a few fundamental principles should be kept in mind. There is a strong correlation between porogen polarity, MIP microenvironment polarity and the imprinting effect itself. The combination of these parameters eventually determines the overall binding behavior of a MIP in a given solvent. In addition, it is shown that MIP binding is strongly influenced by the polarity of the rebinding solvent. Because the use of MIPs in biomedical environments is of considerable interest, it is important that these MIPs perform well in aqueous media. In this article, various approaches are explored towards a water compatible MIP for the target molecule l-nicotine. To this end, the imprinting effect together with the MIP matrix polarity is fine-tuned during MIP synthesis. The binding behavior of the resulting MIPs is evaluated by performing batch rebinding experiments that makes it possible to select the most suitable MIP/non-imprinted polymer couple for future application in aqueous environments. One method to achieve improved compatibility with water is referred to as porogen tuning, in which porogens of varying polarities are used. It is demonstrated that, especially when multiple porogens are mixed, this approach can lead to superior performance in aqueous environments. Another method involves the incorporation of polar or non-polar comonomers in the MIP matrix. It is shown that by carefully selecting these monomers, it is also possible to obtain MIPs, which can selectively bind their target in water. © 2012 John Wiley & Sons, Ltd

Molecularly imprinted polymers as synthetic receptors for the QCM-D-based detection of L-nicotine in diluted saliva and urine samples

Molecularly imprinted polymers (MIPs) are synthetic receptors that are able to specifically bind their target molecules in complex samples, making them a versatile tool in biosensor technology. The combination of MIPs as a recognition element with quartz crystal microbalances (QCM-D with dissipation monitoring) gives a straightforward and sensitive device, which can simultaneously measure frequency and dissipation changes. In this work, bulk-polymerized L-nicotine MIPs were used to test the feasibility of L-nicotine detection in saliva and urine samples. First, L-nicotine-spiked saliva and urine were measured after dilution in demineralized water and 0.1× phosphate-buffered saline solution for proof-of-concept purposes. L-nicotine could indeed be detected specifically in the biologically relevant micromolar concentration range. After successfully testing on spiked samples, saliva was analyzed, which was collected during chewing of either nicotine tablets with different concentrations or of smokeless tobacco. The MIPs in combination with QCM-D were able to distinguish clearly between these samples: This proves the functioning of the concept with saliva, which mediates the oral uptake of nicotine as an alternative to the consumption of cigarettes.status: publishe

Molecularly imprinted polymers as synthetic receptors for the QCM-D-based detection of L-nicotine in diluted saliva and urine samples

Molecularly imprinted polymers (MIPs) are synthetic receptors that are able to specifically bind their target molecules in complex samples, making them a versatile tool in biosensor technology. The combination of MIPs as a recognition element with quartz crystal microbalances (QCM-D with dissipation monitoring) gives a straightforward and sensitive device, which can simultaneously measure frequency and dissipation changes. In this work, bulk-polymerized L-nicotine MIPs were used to test the feasibility of L-nicotine detection in saliva and urine samples. First, L-nicotine-spiked saliva and urine were measured after dilution in demineralized water and 0.1? phosphate-buffered saline solution for proof-of-concept purposes. L-nicotine could indeed be detected specifically in the biologically relevant micromolar concentration range. After successfully testing on spiked samples, saliva was analyzed, which was collected during chewing of either nicotine tablets with different concentrations or of smokeless tobacco. The MIPs in combination with QCM-D were able to distinguish clearly between these samples: This proves the functioning of the concept with saliva, which mediates the oral uptake of nicotine as an alternative to the consumption of cigarettes

MIP-based sensor platforms for the detection of histamine in the nano- and micromolar range in aqueous media

The need for more advanced, accurate and lower cost sensor platforms is constantly growing. However, for certain applications the already existing sensing systems based on biological recognition elements have sometimes restrictions, which limit their use. As a result, sensors with synthetic recognition elements, such as molecular imprinted polymers (MIPs), can be interesting alternatives. Molecular imprinting leads to the formation of inert polymer particles with nanocavities, which can exhibit similar selectivity and specificity to target molecules as antibodies or enzymes. It is demonstrated that MIPs can be readily incorporated into two different sensor platforms for the detection of histamine in aqueous media. The first platform is based on electrochemical impedance spectroscopy and allows for the accurate detection of histamine in the nanomolar range. The second sensing technique is based on microgravimetry and allows for the detection of histamine in the micromolar range. Using the analogous molecule histidine, it is demonstrated that both sensor platforms are specific for the detection of histamine. © 2010 Elsevier B.V.status: publishe

A MIP-based biomimetic sensor for the impedimetric detection of histamine in different pH environments

The development of novel biosensors is arapidly growingfield. Substituting the biological receptor layer from the biosensor with a synthetic receptor opens the door for the development of biomimetic sensors that are chemically and physically inert, as opposed to the sensors containing biological recognition elements. Using molecularly imprinted polymers (MIPs) the specificity and affinity of biological receptors can be mimicked. In addition, a MIP-based sensor can measure in harsh environments. Histamine occurs in harsh environments in food and bodily fluids and is chosen as the target molecule for impedimetric detection. When 10nM histamine is present in pH neutral environments, the impedance increases 45% with respect to the impedance of the sensor without histamine. Specificity is tested with respect to histidine. The influence of the pH on the performance of the sensor is tested. In a pH range of pH 5-12 the MIPs are stable, although they exhibit a varying degree of protonation. The same holds true for the target molecule of which the protonation also varies with the pH of the solution. It is shown that the pH dependent degree of protonation of both the MIP and the histamine has a large impact on the bindingof histamine to the nanocavity in the MIP. Hence, the detection of histamine by a MIP-based sensor is affected by the pH of the solution. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.status: publishe

Heat-transfer-based detection of L-nicotine, histamine, and serotonin using molecularly imprinted polymers as biomimetic receptors

In this work, we will present a novel approach for the detection of small molecules with molecularly imprinted polymer (MIP)-type receptors. This heat-transfer method (HTM) is based on the change in heat-transfer resistance imposed upon binding of target molecules to the MIP nanocavities. Simultaneously with that technique, the impedance is measured to validate the results. For proof-of-principle purposes, aluminum electrodes are functionalized with MIP particles, and L-nicotine measurements are performed in phosphate-buffered saline solutions. To determine if this could be extended to other templates, histamine and serotonin samples in buffer solutions are also studied. The developed sensor platform is proven to be specific for a variety of target molecules, which is in agreement with impedance spectroscopy reference tests. In addition, detection limits in the nanomolar range could be achieved, which is well within the physiologically relevant concentration regime. These limits are comparable to impedance spectroscopy, which is considered one of the state-of-the-art techniques for the analysis of small molecules with MIPs. As a first demonstration of the applicability in biological samples, measurements are performed on saliva samples spiked with L-nicotine. In summary, the combination of MIPs with HTM as a novel readout technique enables fast and low-cost measurements in buffer solutions with the possibility of extending to biological samples.status: publishe