A high sensitivity assay for the inflammatory marker C-Reactive protein employing acoustic biosensing

Advances in the development of biochips, and microfluidic devices in particular, offer the potential to monitor clinically relevant biomarkers in serum or other biological samples with economy in terms of sample volume, reagents and assay time. Whilst these can be semi-automated for higher throughput applications, there is likely to be more impact in small devices for near-patient and point of care applications [1,2].Acoustic biosensors allow label-free detection of biomolecules and analysis of binding events [3,4]. Detection is based on a quartz crystal resonator. The mass of captured analyte by an immobilised receptor molecule on the surface is proportional to the resonant frequency [5]. Today, acoustic sensors are generally based on quartz crystal resonators that are found in common personal electronic devices such as mobile phones, computers and televisions, with over a billion units mass-produced each year [6]. We have developed a novel acoustic detection technology, which we term Resonant Acoustic Profiling (RAP？; [6]). This technology builds on the fundamental basics of the "quartz crystal microbalance" or "QCM". Readout data is generated in real time, which can be analyzed to provide quantitative information including analyte concentration, analyte-receptor interaction specificities, affinities, and kinetics. In this paper we apply RAP to a clinically-relevant application, namely [CRP] estimation.CRP is a classical acute phase reactant discovered by Tillett and Francis in the 1930s [7]. Although a fairly non-specific biomarker, the circulating concentration of CRP rises rapidly (within hours) in response to most forms of tissue damage, infection, and other acute inflammatory events including autoimmune diseases and malignancy. Since CRP can be elevated by as much as 1000-fold over baseline (~100 μg/L to as much as 500 mg/L), monitoring is considered very useful, not just for screening, but also for disease management since the level reflects not only the pre