Profiling of molecular interactions in real time using acoustic detection

Abstract

Acoustic sensors that exploit resonating quartz crystals to directly detect the binding of an analyte to a receptor are finding increasing utility in the quantification of clinically-relevant analytes. We have developed a novel acoustic detection technology, which we term Resonant Acoustic Profiling (RAP™). This technology builds on the fundamental basics of the "quartz crystal microbalance" or "QCM" with several key additional features including two-or four-channel automated sample delivery, in-line referencing and microfluidic sensor 'cassettes' that are pre-coated with easy-to-use surface chemistries. Example applications are described for the quantification of myoglobin concentration and its interaction kinetics, and for the ranking of enzyme-cofactor specificities.

Capabilities of Piezoelectric Immunosensors for Detecting Infections and for Early Clinical Diagnostics

“…To change the viscous-elastic properties of the receptor films which influence the comprehensiveness of contact of the vibrating crystal with the surface, which in turn causes errors in calculating the adsorbed mass. Bi-sensor systems on the basis of high-frequency resonators (16.5 MHz) have been developed for determining mioglobin, a cytoplasmatic protein with the weight of 17 D , a part of muscular cells (Godber et al 2007), the presence of which in blood serves as a good diagnostic marker of cardiac diseases (Casey 2004). The receptor layer of the indicator sensor includes anti-mouse-Fc-specific antibodies in the rabbit which are immobilized by means of EDC and NHS.…”

Target Profiling of Small Molecules

“…Unfortunately, interaction characterization with QCM is still geared toward detailed and low-throughput interaction analysis, even though the drive toward multiplexing and increasing the throughput of the approach is evident. For instance, the RAP id -4 system introduced in 2006 by Akubio Technologies employs the basic principles of QCM along with some variations, and makes possible automated monitoring of SM-protein interactions [25]. The system was demonstrated to rank three cofactors of glucose dehydrogenase correctly according to measured binding response.…”

A miniaturized flow reaction chamber for use in combination with QCM-D sensing

“…For economical and feasibility reasons, it is therefore of great interest to significantly reduced consumption of these materials when possible. Consequently, different sensing techniques have been combined with microfluidic systems; for example surface plasmon resonance (SPR) (Sjölander and Urbaniczky 1991;Wheeler et al 2004), fluorescence microscopy (Marie et al 2006;Satoh et al 2007), SPR-induced fluorescence (Wiltschi et al 2006), electrochemical impedimetric spectroscopy (EIS) (Zou et al 2007), other impedance-based techniques (Ateya et al 2005;Boehm et al 2007), resonant acoustic profiling (RAP) (or quartz crystal microbalance, QCM) (Godber et al 2007), and surface acoustic wave sensors (SAW) (Länge et al 2006;Mitsakakis et al 2008).…”