Xiao Zhu Fan

Integration of genetically modified virus-like- particles with an optical resonator for selective bio-detection

A novel virus-like particle (TMV-VLP) receptor layer has been integrated with an optical microdisk resonator transducer for biosensing applications. This bioreceptor layer is functionalized with selective peptides that encode unique recognition affinities. Integration of bioreceptors with sensor platforms is very challenging due their very different compatibility regimes. The TMV-VLP nanoreceptor exhibits integration robustness, including the ability for self-assembly along with traditional top-down microfabrication processes. An optical microdisk resonator has been functionalized for antibody binding with this receptor, demonstrating resonant wavelength shifts of (Δλo) of 0.79 nm and 5.95 nm after primary antibody binding and enzyme-linked immunosorbent assay (ELISA), respectively, illustrating label-free sensing of this bonding event. This demonstration of label-free sensing with genetically engineered TMV-VLP shows the flexibility and utility of this receptor coating when considering integration with other existing transducer platforms.

Indium Phosphide MEMS Cantilever Resonator Sensors Utilizing a Pentacene Absorption Layer

We report a microelectromechanical system cantilever waveguide resonator sensing platform utilizing a novel optical readout scheme and the organic semiconductor pentacene as a surface absorbing layer. In this paper, the measurement of isopropyl alcohol and ethanol vapors by way of mass induced frequency shift using a cantilever microbalance is demonstrated. Vapor was introduced to the system through a custom built environmental chamber. A frequency shift due to a mass absorption of 65 Hz was measured, corresponding to a measurement of 6.92 ±1.1 ×10-14 g with a minimum detectable mass of 5.09 ×10-15 g for the devices presented. The pentacene absorbing layer in this paper shows it for the first time, functioning as a mass absorbing layer. These results are also the first demonstration of repeatable mass sensing performed using the integrated indium phosphide cantilever waveguide sensor platform.

Real-time monitoring of macromolecular biosensing probe self-assembly and on-chip ELISA using impedimetric microsensors

This paper presents a comprehensive study of the self-assembly dynamics and the biosensing efficacy of Tobacco mosaic virus-like particle (TMV VLP) sensing probes using an impedimetric microsensor platform. TMV VLPs are high surface area macromolecules with nanorod structures constructed from helical arrangements of thousands of identical coat proteins. Genetically modified TMV VLPs express both surface attachment-promoting cysteine residues and FLAG-tag antibody binding peptides on their coat protein outer surfaces, making them selective biosensing probes with self-assembly capability on sensors. The VLP self-assembly dynamics were studied by the continuous monitoring of impedance changes at 100Hz using interdigitated impedimetric microsensors. Electrical impedance spectroscopy revealed VLP saturation on impedance sensor surface with the coverage of 68% in self-assembly process. The VLP-functionalized impedance sensors responded to 12ng/ml to 1.2μg/ml of target anti-FLAG IgG antibodies in the subsequent enzyme-linked immunosorbent assays (ELISA), and yielded 18-35% total impedance increases, respectively. The detection limit of the target antibody is 9.1ng/ml using the VLP-based impedimetric microsensor. These results highlight the significant potential of genetically modified VLPs as selective nanostructured probes for autonomous sensor functionalization and enhanced biosensing.

An adaptive feedback circuit for MEMS resonators

The first adaptive feedback circuit capable of detecting resonant frequencies for a wide range of MEMS resonators is presented. The feedback system presented implements a hill-climbing algorithm that sweeps actuation frequencies, locking onto the resonance condition at maximum cantilever amplitude response without limitations on the frequency range. To demonstrate its adaptability, a circuit implementation of this feedback algorithm was used to detect the resonant frequency of eight different cantilever-based sensors (width (W) = 1.4 µm, length (L) = 40–75 µm, and thickness (T) = 1.8 µm), resonating at 201.0 to 592.1 kHz. Additionally, the same circuit was used to track resonant frequency shifts due to isopropanol adsorption on three different chemical sensors with no modifications. The feedback electronics integrated with these resonator sensors provide a mass resolution limit of 123 femptograms. The realization of this system will enable real-time chip-scale sensor systems, providing an alternative to external instrumentation modules that perform sensor control and monitoring.

Indium phosphide-based monolithically integrated PIN waveguide photodiode readout for resonant cantilever sensors

An integrated photodiode displacement readout scheme for a microelectromechanical cantilever waveguide resonator sensing platform is presented. III-V semiconductors are used to enable the monolithic integration of passive waveguides with active optical components. This work builds upon previously demonstrated results by measuring the displacement of cantilever waveguide resonators with on-chip waveguide PIN photodiodes. The on-chip integration of the readout provides an additional 70% improvement in mass sensitivity compared to off-chip photodetector designs due to measurement stability and minimized coupling loss. In addition to increased measurement stability, reduced packaging complexity is achieved due to the simplicity of the readout design. We have fabricated cantilever waveguides with integrated photodetectors and experimentally characterized these cantilever sensors with monolithically integrated PIN photodiodes.

Virus directed assembly of receptor peptides for explosive sensing

Protein engineering is a rich technology that can be used for chemical vapor detection applications. By utilizing the high specificity and programmability offered by genetic engineering of proteins, a highly selective receptor layer targeting trinitrotoluene (TNT) vapor is developed. This receptor layer consists of a scaffolding made of Tobacco mosaic virus (TMV), whose virus coat protein has been mutated to express cysteine residues and sequence specific peptides to enhance virus self-assembly and selective binding to TNT molecules, respectively. The virus-based receptor layer was assembled on to quartz crystal microbalances (QCMs) for TNT vapor sensing. A 300% increase in TNT attachment was observed on the receptor layer compared to an uncoated QCM. The mass resolution limit was determined to be 3.2ng, limited by the minimum resolution of the current setup. This development demonstrates the potential for programmable viruses to be used as a receptor layer template.

Indium Phosphide Resonant Chemical Sensor with a Monolithically Integrated Optical Readout Scheme

We present a novel MEMS cantilever waveguide resonator sensing platform utilizing for the first time an integrated photodiode readout scheme. This platform uses indium phosphide (InP) to enable the monolithic integration of passive waveguides with active optical components. Cantilever waveguide resonators were successfully fabricated with integrated PIN photodiodes for displacement measurement. On-chip integration of the readout provides a 70% improvement in mass sensitivity compared to off-chip photodetector designs. We have successfully fabricated cantilever waveguides with integrated photodetectors and experimentally characterize these cantilever sensors with monolithically integrated PIN photodiodes.

Vibration-Based Diagnostics for Rotary MEMS

This paper demonstrates the use of low-cost off-the-shelf (OTS) microelectromechanical system (MEMS) technology to perform vibration-based in situ monitoring, diagnostics, and characterization of a MEMS microball bearing supported radial air turbine platform. A multimodal software suite for platform automation and sensor monitoring is demonstrated using a three-level heuristic software suite and sensor network. The vibration diagnostic methods used in the platform have applications in rotary microsystems for the early detection of failure, fault diagnosis, and integrated diagnostic systems for feedback-based optimization to increase device performance, reliability, and operational lifetimes. The studied rotary microdevice used a dual OTS accelerometer configuration for dual range parallel redundant vibration analysis. The sensor suite has been used to monitor and detect multiple operational parameters measured optimally in time or frequency domains such as rotor instability, imbalance, wobble, and system resonance. This paper will lay the framework for active diagnostics in future MEMS devices through integrated systems.

A chemical sensing microsystem utilizing an adaptive feedback circuit

For the first time, a chemical sensor utilizing optical MEMS with a novel adaptive feedback circuit is presented. This circuit implementation of a hill climbing feedback algorithm is capable of autonomously detecting resonant frequency shifts for a range of MEMS resonators. Eight different cantilever-based sensors (width = 0.6–1.4µm, length = 40–75µm, and thickness = 1.8µm), resonating between 200kHz to 600kHz, have been measured. Additionally, the circuit has been used to track resonant frequency shifts due to isopropanol (IPA) adsorption on three different chemical sensors. The frequency detection range, measurement resolution, and sensitivity of the system have been evaluated.

Towards a smart adaptive feedback circuit for microsensors

Integrating electronic circuits with micro-electromechanical systems (MEMS) will enable them to be smart, versatile, and potentially portable due to the intelligence of electronic circuitry, high sensitivity of MEMS device, and size of electrical components. We present a smart sensor system that utilizes a circuits compact real-time instrumentation and readout with a MEMS resonators high sensitivity detection of target analytes. The purpose of the feedback circuit is its integration with a developed in-plane III-V optical resonator system for chemical and biological detection. A resonator sensor utilizes the high sensitivity of cantilevers resonant frequency shift to absorbed mass. Using an integrated system, it will facilitate the testing and data acquisition by replacing multiple macro instrumentation modules. The feedback circuit is based on an optimization algorithm, which is implemented with mixed-signal design using discrete IC components on a circuit board, to track the resonant frequency of a cantilever.