Molecularly imprinted polymers (MIPs) have emerged over the past few decades as interesting synthetic alternatives due to their long-term chemical and physical stability and low-cost synthesis procedure. They have been integrated into many sensing platforms and assay formats for the detection of various targets, ranging from small molecules to macromolecular entities such as pathogens and whole cells. Despite the advantages MIPs have over natural receptors in terms of commercialization, the striking success stories of biosensor applications such as the glucose meter or the self-test for pregnancy have not been matched by MIP-based sensor or detection kits yet. In this review, we zoom in on the commercial potential of MIP technology and aim to summarize the latest developments in their commercialization and integration into sensors and assays with high commercial potential. We will also analyze which bottlenecks are inflicting with commercialization and how recent advances in commercial MIP synthesis could overcome these obstacles in order for MIPs to truly achieve their commercial potential in the near future.

MIPs for commercial application in low-cost sensors and assays - An overview of the current status quo

The exploration of nanomaterials with mimic enzyme activity (named nanozyme) has gained extensive attention in the fields of advanced analytical chemistry and materials science. Herein, the gold nanoparticles doped covalent organic frameworks (COFs) were prepared, which exhibited not only excellent mimic nitroreductase activity but also robust stability. By replacing the traditional natural enzyme tag in an enzyme-linked immunosorbent assay (ELISA), we employed the proposed nanozyme to label the detecting antibody. According to the catalytic properties of the nanozyme, 4-nitrothiophenol (4-NTP) was introduced as the substrate, which can be transformed to 4-aminothiophenol (4-ATP) in the presence of NaBH4. In a surface enhanced Raman scattering (SERS) assay, 4-ATP was capable of functioning as a powerful bridge to connect the gold nanostars (with excellent SERS performance) by both the Au-S bond and electrostatic force to further produce a Raman "hot spot". Meanwhile, the Raman signal of 4-nitrothiophenol at 1573 cm-1 was weakened, and a new signal at 1591 cm-1 generated by 4-ATP was turned on, leading to the generation of a ratiometric SERS signal. Based on this performance, a ratiometric nanozyme-linked immunosorbent assay (NELISA) strategy was developed delicately, which was applied to detect β-lactoglobulin (allergenic protein) by monitoring the ratiometric signal of I1591/I1573 with a limit of detection (LOD) of 0.01 ng/mL. The linear range is 25.65-6.2 × 104 ng/mL, covering more than 3 orders of magnitude. The developed method showed many advantages such as low-cost, higher recovery, and lower cross-reactivity, providing new insight into the application of SERS technology for trace target analysis.

Ratiometric Surface Enhanced Raman Scattering Immunosorbent Assay of Allergenic Proteins via Covalent Organic Framework Composite Material Based Nanozyme Tag Triggered Raman Signal "Turn-on" and Amplification.

The strong affinity of biological receptors for their targets has been studied for many years. Noncovalent interactions between these natural recognition elements and their ligands form the basis for a broad range of biosensor applications. Although these sensing platforms are usually appreciably sensitive and selective, certain drawbacks are associated with biological receptors under nonphysiological conditions in terms of temperature, pH, or ionic strength. Therefore, there are considerable efforts to mimic such molecular interactions with robust, synthetic receptors. Molecular imprinting is the best-known technique to obtain antibody mimics by synthesizing a polymer matrix in the presence of a template species, such as molecules or larger aggregates. Extraction of the template results in sterically and functionally adapted binding cavities in or on a porous matrix. Although in principle possible, the detection of larger bioparticles such as proteins, microorganisms, or cells remains challenging when us...

A Review on Synthetic Receptors for Bioparticle Detection Created by Surface-Imprinting Techniques—From Principles to Applications

Food allergies are a type I hypersensitivity immune responses that can be life threatening. While exposure therapy and urgent care interventions can limit the damage of an allergic episode, there is currently no cure for food hypersensitivities. Many patients will experience an accidental exposure to a known allergen due to the complexity of food preparation methods in the modern diet. One method of avoidance is to monitor food with point of care (POC) biosensors that can detect known allergens. These detectors are categorized according to their sensor mechanism, such as optical, electromechanical, and electrochemical biosensors. More innovations that are recent combine biosensors with genosensors and cell assays. Major challenges to allergen monitoring include the introduction of new allergens into modern diets, the rising incidence hypersensitivities, lack of clinical understanding of the types and causes of food allergies, limited commercial availability of biosensors, and the lack of international standards or agreement on threshold detection levels. Public health leaders are taking on these challenges, and their efforts will reduce the incidence of preventable exposures and improve overall food safety management.

Nano-biosensor platforms for detecting food allergens – New trends

Triggering unpredictable allergic reactions associated with the presence of hidden allergens in the food chains have raised the need for precise, fast and reliable analytical methods to identify food allergens in different sources. Unintentional cross contamination of food products with allergen sources during production, transformation or processing is also an important risk factor for triggering allergenic reactions in suspected individuals. Different types of antibody based detection methods are applied for detection and standardization of food-born allergens. Aptamers attracted a great attention because of their small size, low cast and ease of manufacturing. Several detection strategies have been investigated for food allergen aptasensing such as electrochemical, optical, thermometric and piezoelectric. In this review, advances and the future trends of developed aptasensors for the control and detection of food-born allergens have been discussed.

Detection of food-born allergens with aptamer-based biosensors

Aptamers are an emerging class of molecules that, because of the development of the systematic evolution of ligands by exponential enrichment (SELEX) process, can recognize virtually every target ranging from ions, to proteins, and even whole cells. Although there are many techniques capable of detecting template molecules with aptamer-based systems with high specificity and selectivity, they lack the possibility of integrating them into a compact and portable biosensor setup. Therefore, we will present the heat-transfer method (HTM) as an interesting alternative because this offers detection in a fast and low-cost manner and has the possibility of performing experiments with a fully integrated device. This concept has been demonstrated for a variety of applications including DNA mutation analysis and screening of cancer cells. To the best our knowledge, this is the first report on HTM-based detection of proteins, in this case specifically with aptamer-type receptors. For proof-of-principle purposes, measurements will be performed with the peanut allergen Ara h 1 and results indicate detection limits in the lower nanomolar regime in buffer liquid. As a first proof-of-application, spiked Ara h 1 solutions will be studied in a food matrix of dissolved peanut butter. Reference experiments with the quartz-crystal microbalance will allow for an estimate of the areal density of aptamer molecules on the sensor-chip surface.

/pdf/label-free-protein-detection-based-on-the-heat-transfer-1f8922c3ht.pdf

Label-free protein detection based on the heat-transfer method-a case study with the peanut allergen Ara h 1 and aptamer-based synthetic receptors

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Label-free protein detection based on the heat-transfer method-a case study with the peanut allergen Ara h 1 and aptamer-based synthetic receptors