Review of Transducer Principles for Label-Free Biomolecular Interaction Analysis

Abstract

Label-free biomolecular interaction analysis is an important technique to study the chemical binding between e.g., protein and protein or protein and small molecule in real-time. The parameters obtained with this technique, such as the affinity, are important for drug development. While the surface plasmon resonance (SPR) instruments are most widely used, new types of sensors are emerging. These developments are generally driven by the need for higher throughput, lower sample consumption or by the need of complimentary information to the SPR data. This review aims to give an overview about a wide range of sensor transducers, the working principles and the peculiarities of each technology, e.g., concerning the set-up, sensitivity, sensor size or required sample volume. Starting from optical technologies like the SPR and waveguide based sensors, acoustic sensors like the quartz crystal microbalance (QCM) and the film bulk acoustic resonator (FBAR), calorimetric and electrochemical sensors are covered. Technologies long established in the market are presented together with those newly commercially available and with technologies in the early development stage. Finally, the commercially available instruments are summarized together with their sensitivity and the number of sensors usable in parallel and an outlook for potential future developments is given.

Immunodiagnostics and immunosensor design (IUPAC Technical Report)

“…The label-free transducer principles are typically based on a variety of responses, including increase of mass-induced mechanical deflection (cantilever) [78,79] shown in Fig. 8, mass spectrometry [80], mass-induced change of gold/silver surface light reflection surface plasmon resonance [81], electrical potential changes [82,83], change of the inner heat (calorimetry) [84], acoustic or surface acoustic wave detection [85], surface-enhanced Raman scattering [86], and piezoelectric or piezoresistive platforms [87,88], among others (Table 1). Label-free detection methods have been used primarily for in-depth characterization of biomolecule interactions.…”

Label-free affinity biosensor arrays: novel technology for molecular diagnostics

“…Much of the research to date has focused on the development and optimization of transducer materials, including a recent emphasis on carbon-based biosensors [3,4], and physiochemical transduction strategies, with transducers that are sensitive to the optical, electrochemical, and mechanical properties of biological molecules receiving most attention. A number of comprehensive review articles have been published that focus on biosensor transduction strategies [5][6][7]. There is also a significant body of work on optimized surface chemistries for antibody immobilization and alternative high-affinity binding agents such as antibody fragments, DNA and peptide aptamers, and molecularly imprinted polymers [8].…”

Tackling reproducibility in microcantilever biosensors: a statistical approach for sensitive and specific end-point detection of immunoreactions

“…Moreover, it can alter the biological activity of the labelled molecule, altering the result of the assay [1][2] . Label-free bioassays rely on the measurement of an inherent property of the targeted molecules 1,3 . The most widespread biosensors based on this concept are the quartz crystal microbalance and the surface plasmon resonance sensor.…”