Jessica L. Arlett

Comparative advantages of mechanical biosensors

Mechanical interactions are fundamental to biology. Mechanical forces of chemical origin determine motility and adhesion on the cellular scale, and govern transport and affinity on the molecular scale. Biological sensing in the mechanical domain provides unique opportunities to measure forces, displacements and mass changes from cellular and subcellular processes. Nanomechanical systems are particularly well matched in size with molecular interactions, and provide a basis for biological probes with single-molecule sensitivity. Here we review micro- and nanoscale biosensors, with a particular focus on fast mechanical biosensing in fluid by mass- and force-based methods, and the challenges presented by non-specific interactions. We explain the general issues that will be critical to the success of any type of next-generation mechanical biosensor, such as the need to improve intrinsic device performance, fabrication reproducibility and system integration. We also discuss the need for a greater understanding of analyte-sensor interactions on the nanoscale and of stochastic processes in the sensing environment.

Sensitive detection of nanomechanical motion using piezoresistive signal downmixing

We have developed a method of measuring rf-range resonance properties of nanoelectromechanical systems (NEMS) with integrated piezoresistive strain detectors serving as signal downmixers. The technique takes advantage of the high strain sensitivity of semiconductor-based piezoresistors, while overcoming the problem of rf signal attenuation due to a high source impedance. Our technique also greatly reduces the effect of the cross-talk between the detector and actuator circuits. We achieve thermomechanical noise detection of cantilever resonance modes up to 71 MHz at room temperature, demonstrating that downmixed piezoresistive signal detection is a viable high-sensitivity method of displacement detection in high-frequency NEMS.

Ultimate and practical limits of fluid-based mass detection with suspended microchannel resonators

Suspended microchannel resonators (SMRs) are an innovative approach to fluid-based microelectromechanical mass sensing that circumvents complete immersion of the sensor. By embedding the fluidics within the device itself, vacuum-based operation of the resonator becomes possible. This enables frequency shift-based mass detection with high quality factors, and hence sensitivity comparable to vacuum-based micromechanical resonators. Here we present a detailed analysis of the sensitivity of these devices, including consideration of fundamental and practical noise limits, and the important role of binding kinetics in sensing. We demonstrate that these devices show significant promise for protein detection. For larger, biologically-important targets such as rare whole virions, the required analysis time to flow sufficient sample through the sensor can become prohibitively long unless large parallel arrays of sensors or preconcentrators are employed.

BioNEMS: Nanomechanical Systems for Single-Molecule Biophysics

Techniques from nanoscience now enable the creation of ultrasmall electronic devices. Among these, nanoelectromechanical systems (NEMS) in particular offer unprecedented opportunities for sensitive chemical, biological, and physical measurements [1]. For vacuum-based applications NEMS provide extremely high force and mass sensitivity, ultimately below the attonewton and single-Dalton level respectively. In fluidic media, even though the high quality factors attainable in vacuum become precipitously damped due to fluid coupling, extremely small device size and high compliance still yield force sensitivity at the piconewton level - i.e., smaller than that, on average, required to break individual hydrogen bonds that are the fundamental structural elements underlying molecular recognition processes. A profound and unique new feature of nanoscale fluid-based mechanical sensors is that they offer the advantage of unprecedented signal bandwidth (»1 MHz), even at piconewton force levels. Their combined sensitivity and temporal resolution is destined to enable real-time observations of stochastic single-molecular biochemical processes down to the sub-microsecond regime [2].