A Versatile Planar QCM-Based Sensor Design for Nonlabeling Biomolecule Detection

Abstract

Despite high theoretical sensitivity, low-cost manufacture, and compactness potentially amenable to lab-on-a-chip use, practical hurdles have stymied the application of the quartz crystal microbalance (QCM) for aqueous applications such as detection of biomolecular interactions. The chief difficulty lies in achieving a sufficiently stable resonance signal in the presence of even minute fluctuations in hydrostatic pressure. In this work, we present a novel versatile planar sensor chip design (QCM chip) for a microliter-scale on-line biosensor. By sealing the quartz resonator along its edges to a flat, solid support, we provide uniform support for the crystal face not exposed to solvent, greatly decreasing deformation of the crystal resonator under hydrostatic pressure. Furthermore, this cassette design obviates the need for direct handling when exchanging the delicate quartz crystal in the flow cell. A prototype 27-MHz sensor signal exhibited very low noise over a range of flow rates up to 100 microL/min. In contrast, signals obtained from a conventional QCM sensor employing an O-ring-based holder were less stable and deteriorated even further with increasing flow rate. Additional control designs with intermediate amounts of unsupported undersurface yielded intermediate levels of stability, consistent with the interpretation that deformation of the crystal resonator under fluctuating hydraulic pressure is the chief source of noise. As a practical demonstration of the design's high effective sensitivity, we readily detected interaction between myoglobin and surface-bound antibody.

High-frequency phase shift measurement greatly enhances the sensitivity of QCM immunosensors

“…HFF resonators are usually described as small, fragile and difficult to implement in flow-cell systems (Lin et al, 1993;Sagmeister et al, 2009;Stehrer et al, 2010). Moreover, these sensors do not quite get a stable resonance frequency signal in the presence of even minute fluctuations of hydrostatic pressure (Sota et al, 2002).…”

A survey of the 2001 to 2005 quartz crystal microbalance biosensor literature: applications of acoustic physics to the analysis of biomolecular interactions

“…QCM-D, on the other hand, produced measured values that were generally higher in terms of mass. This, in turn, provided valuable, complementary information in two respects: (i) the mass calculated from the resonant frequency shift included both protein mass and water that binds or hydrodynamically (Sota et al, 2002). couples to the protein adlayer; and (ii) analysis of the energy dissipation in the adlayer and its magnitude in relation to the frequency shift (cf. adsorbed mass) provided insight about the mechanical/structural (viscoelastic) properties of the layer.…”

Design, fabrication, and packaging of a practical multianalyte-capable optical biosensor

“…[9][10][11][12][13][14] The last three factors in particular are not usually considered primary in academic design, as they are normally only significant if a device is intended for commercial applications. Since practicality of the device design was a deciding condition, these factors were considered throughout the entire design and development process.…”