Real-Time Bio Sensing Using Micro-Channel Encapsulated MEMS Resonators

This work presents a label-free bio-molecular detection technique based on realtime monitoring of the resonant frequency of micromechanical thermal-piezoresistive rotational mode disk resonators encapsulated in microfluidic channels. Mass loading via adsorption of molecular layers on the surface of such devices results in a frequency shift. In order to provide a reliable platform for sample-resonator interactions and to protect the resonators from contaminants, the resonators were encapsulated in PDMS-based microfluidic channels. Micro-channel encapsulation also allows insulation of electrical signals from the analyte solution. To characterize the performance of such devices as real-time label-free bio-molecular detectors, the strong non-covalent binding of Avidin with its ligand, biotin was utilized. To further validate the measured frequency shifts and confirm that the frequency shifts are due to molecular attachments to the resonator surfaces, fluorescent labeled molecules followed by fluorescent imaging was used confirming the existence of the expected molecular layers on the resonator surfaces

Wireless Intraocular Pressure Sensing Using Microfabricated Minimally Invasive Flexible-Coiled LC Sensor Implant

This paper presents an implant-based wireless pressure sensing paradigm for long-range continuous intraocular pressure (IOP) monitoring of glaucoma patients. An implantable parylene-based pressure sensor has been developed, featuring an electrical LC-tank resonant circuit for passive wireless sensing without power consumption on the implanted site. The sensor is microfabricated with the use of parylene C (poly-chlorop- xylylene) to create a flexible coil substrate that can be folded for smaller physical form factor so as to achieve minimally invasive implantation, while stretched back without damage for enhanced inductive sensor–reader coil coupling so as to achieve strong sensing signal. A data-processed external readout method has also been developed to support pressure measurements. By incorporating the LC sensor and the readout method, wireless pressure sensing with 1-mmHg resolution in longer than 2-cm distance is successfully demonstrated. Other than extensive on-bench characterization, device testing through six-month chronic in vivo and acute ex vivo animal studies has verified the feasibility and efficacy of the sensor implant in the surgical aspect, including robust fixation and long-term biocompatibility in the intraocular environment. With meeting specifications of practical wireless pressure sensing and further reader development, this sensing methodology is promising for continuous, convenient, direct, and faithful IOP monitoring

Advances in High-Speed Atomic Force Microscopy

High-speed atomic force microscopy (HS-AFM) is a scanning probe technique capable of recording processes at the nanometre scale in real time. By sequentially increasing the speed of individual microscope components, images of surfaces can be recorded at up to several images per second. We present a HS-AFM platform composed of custom¿built measurement head, controller and software, scanners and amplifiers that is shared with the community in an open¿hardware fashion. A new scanner design combined with an advanced control system is shown. The simple addition of a secondary actuator to widely available tube scanners increases the scan speed by over an order of magnitude while allowing for a 130 ¿m × 130 ¿m wide field of view, which is not possible with traditional high¿speed scanner designs. Controllers beyond standard proportional-integral controllers are capable of significantly increasing imaging speed by anticipating resonances. Such filters are cumbersome to design with conventional methods. It is shown how convex optimization can be used to design optimal controllers with guaranteed stability for atomic force microscopy in an automated fashion. By integrating two lasers into the small spot¿size optics of an AFM readout head we are able to use the first laser for detecting the deflection of the smallest, and thus fastest currently available high¿speed cantilevers, while using the second for photo¿thermal actuation. Using this instrument, we demonstrate multi¿frequency atomic force microscopy (MF-AFM) at previously not accessible frequencies of more than 20 MHz. By employing the driving laser not for resonant excitation as is usual in dynamic AFM, a new imaging mode, photothermal off-resonance tapping (PORT) is presented. By repeatedly thermally bending the cantilever below it¿s resonant frequency, the surface is probed at a rapid rate. The resulting force is extracted from the deflection of the cantilever in time¿ domain at real time and used for feedback and image generation. The dynamic and static force contributions in both PORT and state of the art high-speed amplitude modulation atomic force microscopy (AM-AFM) are measured and analyzed in detail. It is shown that by decoupling the driving frequency from the resonant frequency the dynamic tip¿sample impact forces can be drastically reduced when compared to resonance based AFM modes. SAS-6 is a centriolar scaffolding protein with a crucial role in the duplication of centrioles, which are the main microtubule organizing organelle of eukaryotic cells. Defects in centriole duplication are associated with cancer and microencephaly. To understand these defects, is therefore important to understand the kinetics of SAS-6. In¿vitro, SAS-6 polymerizes into rings of between eight and ten monomers. Using the new PORT mode we are able to study the dynamic assembly of SAS-6. It is shown how SAS-6 rings can not only assemble by canonical one-by-one addition, but can form as a fusion of larger, already assembled fragments. Finally, it is shown how PORT can be used to observe fast processes of and on living cells. The adhesion and detachment of thrombocyte cells is studied. Membrane disruptive effects are shown on gram¿negative as well as gram¿positive bacteria

Bulk and Surface Acoustic Wave Sensor Arrays for Multi-Analyte Detection: A Review

Bulk acoustic wave (BAW) and surface acoustic wave (SAW) sensor devices have successfully been used in a wide variety of gas sensing, liquid sensing, and biosensing applications. Devices include BAW sensors using thickness shear modes and SAW sensors using Rayleigh waves or horizontally polarized shear waves (HPSWs). Analyte specificity and selectivity of the sensors are determined by the sensor coatings. If a group of analytes is to be detected or if only selective coatings (i.e., coatings responding to more than one analyte) are available, the use of multi-sensor arrays is advantageous, as the evaluation of the resulting signal patterns allows qualitative and quantitative characterization of the sample. Virtual sensor arrays utilize only one sensor but combine itwith enhanced signal evaluation methods or preceding sample separation, which results in similar results as obtained with multi-sensor arrays. Both array types have shown to be promising with regard to system integration and low costs. This review discusses principles and design considerations for acoustic multi-sensor and virtual sensor arrays and outlines the use of these arrays in multi-analyte detection applications, focusing mainly on developments of the past decade

Validation of a Phase-Mass Characterization Concept and Interface for Acoustic Biosensors

Acoustic wave resonator techniques are widely used in in-liquid biochemical applications. The main challenges remaining are the improvement of sensitivity and limit of detection, as well as multianalysis capabilities and reliability. The sensitivity improvement issue has been addressed by increasing the sensor frequency, using different techniques such as high fundamental frequency quartz crystal microbalances (QCMs), surface generated acoustic waves (SGAWs) and film bulk acoustic resonators (FBARs). However, this sensitivity improvement has not been completely matched in terms of limit of detection. The decrease on frequency stability due to the increase of the phase noise, particularly in oscillators, has made it impossible to increase the resolution. A new concept of sensor characterization at constant frequency has been recently proposed based on the phase/mass sensitivity equation: Δφ/Δm ≈ −1/mL, where mL is the liquid mass perturbed by the resonator. The validation of the new concept is presented in this article. An immunosensor application for the detection of a low molecular weight pollutant, the insecticide carbaryl, has been chosen as a validation model

Electronic readout of microchannel resonators for precision mass sensing in solution by Rumi Chunara.

Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2010.Cataloged from PDF version of thesis.Includes bibliographical references (p. 115-120).Microfabricated transducers have enabled new approaches for detection of biomolecules and cells. Integration of electronics with these tools simplify systems and provide platforms for robust use outside of the laboratory setting. Suspended microchannel resonators (SMRs) are sensitive microfluidic platforms used to precisely measure the buoyant mass of single cells and monolayers of protein in fluid environments. Conventionally, micro cantilever deflection is measured by the optical-lever technique, wherein a laser beam is reflected off the cantilever onto a position sensitive photodiode. This thesis introduces microchannel resonators with electronic readout, eliminating the use of external optical components for resolving the sensor's resonant frequency. Piezo resistors have been fabricated on SMRs through ion implantation integrated with the existing SMR fabrication process. We fabricated two designs: one with a cantilever length of 210 pm and resonant frequency of -347 kHz, and the other with a cantilever length of 406 pm and resonant frequency of ~92 kHz. The work here builds upon knowledge of signal transduction from static and dynamic cantilever based sensors because the piezo resistors are implemented on vacuum encapsulated devices containing fluid. Electronic readout is shown to resolve the microchannel resonance frequency with an Allan variance of 5 x 10-18 (210 pm) and 2 x 1017 (406 pm) using a 100ms gate time, corresponding to a mass resolution of 0.1 and 0.4 fg respectively. This mass resolution calculated from piezoresistive readout frequency stability, is approximately 3X better than optical readout for the 210 pm device and 1.3X for the 406 pm device using the same gate time. Resolution is expected to improve with further optimization of the system. To demonstrate the readout, histograms of the buoyant masses of a mixture of size standard polystyrene beads (with nominal diameters 1.6, 1.8, and 2.0 pm) and budding yeast cells were made.Ph.D

Characterization and application of piezoelectric microcantilever sensors fabricated from substrate-free PMN-PT layers

Piezoelectric Microcantilever Sensor (PEMS) has attracted tremendous attention and numerous biological and chemical detections have been demonstrated. During detection, adsorption induced surface stress causes the PEMS flexural resonance frequency shift, however, the sensing mechanism due to stress effect is still unclear. The goal of this dissertation is to carry out fundamental study of sensing mechanism and then demonstrate chemical warfare agent detection.When a PEMS is subject to a DC bias field, the flexural resonance frequency shifted as a result of Young’s modulus change in the PMN-PT layer which was confirmed by the measurement of width mode frequency and the relative dielectric constant measurement indicated that the Young’s modulus change was a result of non-180° domain switching. Similarly, the flexural resonance frequency shift of a PEMS during humidity detection was also due to the Young’s modulus change which was two-order-of-magnitude larger than could be accounted for by the mass loading alone. Furthermore, a negative DC field of -6 kV/cm enhanced the relative resonance frequency shift in humidity detection by more than 3 times of the detection without a DC bias. It was shown that during humidity detection, the frequency shift of the flexural mode, Δf, was inversely proportional to the square of the PEMS length, L2; relative resonance frequency shift, Δf/f, was inversely proportional to the PEMS thickness, t; and the mass detection sensitivity, Δf/Δm, was inversely proportional to wL3 where w is the width.The Young’s modulus change and scaling were validated in another independent system - DMMP detection using SAM MUA/Cu2+ coated PEMS. In addition, the flexural frequency shift of the microporous silica powder coated PEMS followed mass loading model while the planar MPS coated PEMS showed two-order-of-magnitude enhancement indicating a continuous coating of adsorbent on PEMS is desired.Array PMN-PT/Cu PEMSs coated with planar MPS, SAM MUA/Cu2+, and no coating as control can be used to selectively detect DMMP at room temperature. Other gas species such as acetone and ammonia were examined as well using the same array. The resonance frequency shifts of the array PEMSs exhibited a unique pattern in response to DMMP and the detection can be achieved in less than 5 minutes.Ph.D., Materials Engineering -- Drexel University, 200

Metamaterials Application in Sensing

Metamaterials are artificial media structured on a size scale smaller than wavelength of external stimuli, and they can exhibit a strong localization and enhancement of fields, which may provide novel tools to significantly enhance the sensitivity and resolution of sensors, and open new degrees of freedom in sensing design aspect. This paper mainly presents the recent progress concerning metamaterials-based sensing, and detailedly reviews the principle, detecting process and sensitivity of three distinct types of sensors based on metamaterials, as well as their challenges and prospects. Moreover, the design guidelines for each sensor and its performance are compared and summarized