Bioanalytical sensors using the heat-transfer method HTM and related techniques.

This review provides an overview on bio- and chemosensors based on a thermal transducer platform that monitors the thermal interface resistance R th between a solid chip and the supernatant liquid. The R th parameter responds in a surprisingly strong way to molecular-scale changes at the solid-liquid interface, which can be measured thermometrically, using for instance thermocouples in combination with a controllable heat source. In 2012, the effect was first observed during on-chip denaturation experiments on complementary and mismatched DNA duplexes that differ in their melting temperature. Since then, the concept is addressed as heat-transfer method, in short HTM, and numerous applications of the basic sensing principle were identified. Functionalizing the chip with bioreceptors such as molecularly imprinted polymers makes it possible to detect neurotransmitters, inflammation markers, viruses, and environmental pollutants. In combination with aptamer-type receptors, it is also possible to detect proteins at low concentrations. Changing the receptors to surface-imprinted polymers has opened up new possibilities for quantitative bacterial detection and identification in complex matrices. In receptor-free variants, HTM was successfully used to characterize lipid vesicles and eukaryotic cells (yeast strains, cancer cell lines), the latter showing spontaneous detachment under influence of the temperature gradient inherent to HTM. We will also address modifications to the original HTM technique such as M-HTM, inverted HTM, thermal wave transport analysis TWTA, and the hot-wire principle. The article concludes with an assessment of the possibilities and current limitations of the method, together with a technological forecast.

An Overview on Recent Advances in Biomimetic Sensors for the Detection of Perfluoroalkyl Substances.

Per- and polyfluoroalkyl substances (PFAS) are a class of materials that have been widely used in the industrial production of a wide range of products. After decades of bioaccumulation in the environment, research has demonstrated that these compounds are toxic and potentially carcinogenic. Therefore, it is essential to map the extent of the problem to be able to remediate it properly in the next few decades. Current state-of-the-art detection platforms, however, are lab based and therefore too expensive and time-consuming for routine screening. Traditional biosensor tests based on, e.g., lateral flow assays may struggle with the low regulatory levels of PFAS (ng/mL), the complexity of environmental matrices and the presence of coexisting chemicals. Therefore, a lot of research effort has been directed towards the development of biomimetic receptors and their implementation into handheld, low-cost sensors. Numerous research groups have developed PFAS sensors based on molecularly imprinted polymers (MIPs), metal-organic frameworks (MOFs) or aptamers. In order to transform these research efforts into tangible devices and implement them into environmental applications, it is necessary to provide an overview of these research efforts. This review aims to provide this overview and critically compare several technologies to each other to provide a recommendation for the direction of future research efforts focused on the development of the next generation of biomimetic PFAS sensors.

Synchronized, Spontaneous, and Oscillatory Detachment of Eukaryotic Cells: A New Tool for Cell Characterization and Identification.

Despite the importance of cell characterization and identification for diagnostic and therapeutic applications, developing fast and label-free methods without (bio)-chemical markers or surface-engineered receptors remains challenging. Here, we exploit the natural cellular response to mild thermal stimuli and propose a label- and receptor-free method for fast and facile cell characterization. Cell suspensions in a dedicated sensor are exposed to a temperature gradient, which stimulates synchronized and spontaneous cell-detachment with sharply defined time-patterns, a phenomenon unknown from literature. These patterns depend on metabolic activity (controlled through temperature, nutrients, and drugs) and provide a library of cell-type-specific indicators, allowing to distinguish several yeast strains as well as cancer cells. Under specific conditions, synchronized glycolytic-type oscillations are observed during detachment of mammalian and yeast-cell ensembles, providing additional cell-specific signatures. These findings suggest potential applications for cell viability analysis and for assessing the collective response of cancer cells to drugs.

Cell-Imprint Surface Modification by Contact Photolithography-Based Approaches: Direct-Cell Photolithography and Optical Soft Lithography Using PDMS Cell Imprints.

New cell-imprint surface modification techniques based on direct-cell photolithography and optical soft lithography using poly(dimethylsiloxane) (PDMS) cell imprints are presented for enhanced cell-based studies. The core concept of engineering materials for cell-based studies is the material's ability to redesign the physicochemical characteristics of the cellular niche. There is a growing interest in direct molding from cells (cell imprinting). These negative copies of cell surface topographies have been shown to affect cell shape and direct mesenchymal stem cells' differentiation. Analyzing the results is however challenging as cells seeded on these substrates do not always end up in a cell pattern, which leads to decreased effectiveness and biased quantification. To gain control over cell seeding into the patterns and avoid unwanted cell population outside of the patterns, the cell-imprinted surface needs to be modified. From this perspective, the standard optical contact lithography process was modified and cells were introduced to the cleanroom. Direct-cell photolithography was used for a single-step PDMS cell-imprint (chondrocytes as the molding template) surface modification down to single-cell (approximately 5 µm in diameter) resolution. As cells come in a variety of shapes, sizes, and optical profiles, a complementary optical soft lithography-based photomask fabrication technique is also reported. The simplicity of the fabrication process makes this cell-imprint surface modification technique compatible with any adherent cell type and leads to efficient cell-based studies.