The analysis of biomolecular interactions is key in the drug development process. Label-free biosensor methods provide information on binding, kinetics, concentration, and the affinity of an interaction. These techniques provide real-time monitoring of interactions between an immobilized ligand (such as a receptor) to an analyte in solution without the use of labels. Advances in biosensor design and detection using BioLayer Interferometry (BLI) provide a simple platform that enables label-free monitoring of biomolecular interactions without the use of flow cells. We review the applications of BLI in a wide variety of research and development environments for quantifying antibodies and proteins and measuring kinetics parameters.

Many efforts have been made worldwide to develop and improve electrochemical methods for DNA detection with the aim of making portable and affordable devices.[1±4] In spite of many advances in this field, it is still a challenge to find new approaches that could improve the simplicity, selectivity, and sensitivity of DNA detection, in order to respond to the demands and needs of modern medical diagnostics and biomedical research applications. In this regard, some oligonucleotide-functionalized conjugated polymers have enabled the transduction of hybridization events into an electrical signal without labeling of the DNA target.[5±7] However, with this strategy, waterinsoluble electroactive polymers are always present on the electrodes, leading to a strong electrical background. Moreover, in those systems, hybridization often leads to a decrease in the electrical signal. To solve these problems, we propose a new solid-state electrostatic approach based on neutral peptide nucleic acid (PNA) capture probes [8] and an electroactive, cationic, water-soluble polythiophene transducer. [9,10] The solidstate electrochemical detection occurs when the neutral probes are hybridized with a complementary DNA target, leading to an attractive electrostatic interaction with a cationic polythiophene transducer (Scheme 1). A similar electrostatic strategy using fluorescent, cationic, conjugated polymers was recently utilized for the specific optical detection of oligonucleotides on PNA microarrays [10] and in aqueous solution.[11]To implement this new solid-state electrochemical approach, we first prepared gold electrodes with a monolayer of PNA capture probes (see Experimental), and then performed square-wave voltammetry (SWV). The cationic, water-soluble, and electroactive polymer 1 (see Scheme 2) does not bind to neutral PNA capture probes alone (Scheme 1a; Fig. 1, trace a) but interacts strongly with the negatively charged backbone of the complementary oligonucleotide bound to the PNA probes, [10] allowing transduction of room-temperature hybridization into an electrical signal (Scheme 1b; Fig. 1, COMMUNICATIONS

By combining an appropriate DNA aptamer with a cationic polythiophene optical transducer, human thrombin can be specifically detected on microarrays in the attomole range in less than one hour without any tagging of the target. The system can be modified and utilized as a probe for the detection of various proteins or other biomolecules. This work opens new interesting possibilities for simple and rapid multiparametric analysis in genomics and proteomics.

The cover image depicts biochips based on responsive nanoaggregates made from stoichiometric complexes between a cationic polythiophene and an appropriate DNA aptamer. These structures undergo a conformational transition from an unfolded to a folded (G‐quadruplex) structure in the presence of a specific target protein that results in a significant increase of the fluorescence intensity, as reported on p. 2703 by Leclerc and co‐workers.