Gailius Vanagas

Capacitive micromachined ultrasound transducer (cMUT) for immunosensor design

An affinity sensor based on a capacitive micromachined ultrasound transducer (cMUT) is reported by this Communication. The cMUT micromembrane arrays modified with adsorbed bovine leukemia virus protein gp51 were applied as a biological recognition part. The cMUT-based sensor is shown to be sensitive to the antibodies against bovine leukemia virus protein gp51 (anti-gp51). Two different concentrations of anti-gp51-containing samples and one blank sample without anti-gp51 were tested. The sensitivity of cMUT-based immunosensor is comparable with the sensitivity of a quartz microbalance-based immunosensor. The cMUT array provides a multi-channel system for the measurement of analytical signal. Moreover, two different characteristics--the resonance frequency shift (Deltaf) and the shift of the real part of the electromechanical impedance (DeltaRe)--could have been evaluated simultaneously. Both analytical signals are informative and can be applied for the estimation of immune complex formation. We found the performance of such a system being potentially superior over some other immunosensing techniques. It is more rapid than electrochemical techniques and provides two different informative parameters.

Study of the CMUT operation in microfluidic application

Operation of capacitive micromachined ultrasound transducers (CMUT) in comparatively low profile (2-400 μm) fluid-coupled microchannels was studied by numerical simulation. The two-dimensional transient time finite element analysis was used to simulate the transmission of the short pulse and capture the resulting mechanical waves in solid and fluid environments and at the solid-fluid interface. The analysis of the CMUT cell operation during transmission showed that the bulk waves in fluid, which are reflected from the top wall of the microchannel, can affect the performance of the membrane, if the height of the microchannel is below certain critical value. Membrane swing amplitude and central frequency of membrane oscillations can be shifted because of this interaction. As far as these parameters are informative in sensor applications, the design of the CMUT/microchannel system has to be accounted for the microchannel height.

Acoustical Streaming in Microfluidic CMUT Integrated Chip Controls the Biochemical Interaction Rate

Acoustical fluid mixing and streaming in microfluidic chips enhance the detection and fluid routeing capabilities in the lab-on-chip devices. Capacitive micromachined ultrasound transducers (CMUT) are easy to integrate into a closely packed environment, and they can be simultaneously used as integrated sensors and micropumps/mixers. In this paper, particular focus is given to examininge the impact of the acoustical fluid mixing to the kinetics of biochemical interaction. CMUT interdigital transducers for 10-MHz operation in water were designed and fabricated using the surface micromachining technique. Devices use Scholte type waves for biochemical detection and acoustical streaming. They also have the ability to control the directionality of acoustical streaming by +/−90° phase shift. The impact of acoustical streaming to the liquid diffusion kinetics in the microchannel and to the kinetics of adsorption of the bovine serum albumin (BSA) to the gold surface was investigated experimentally. For microfluidic experiments, CMUTs were assembled with 100

CMUT for high sensitivity greenhouse gas sensing

\mu \text{m}

Capacitive micromachined ultrasound transducers (CMUT) for resonant gravimetric immunosensing

deep microchannels. It was determined that acoustical streaming can improve the diffusion rate through the microchannel. Also, it was shown that BSA adsorption rate can be controlled by changing the phase shift during excitation of the Sholte type waves. [2016–0224]

Surface micromachined CMUTs for liquid phase sensing

In our work we address creation of reliable and cross-selective platform of greenhouse gas sensing for environmental monitoring and safety purposes based on capacitive micromachined ultrasound transducers (CMUT) technology. We emphasize the need of cross-selectivity between CO2, CH4 and H2S since mixture of these gases is common in anthropogenic and natural gas emissions, and their impact to the greenhouse effect remains underexplored. CMUT sensors containing five elements with resonance frequencies from 15 to 35 MHz were designed and fabricated by fully CMOS compatible surface micromachining technology. Two parallel measurement channels, one reference and one sensing were arranged to measure the mass loading of the CMUT structure and eliminate the non-informative changes of the working environment as temperature, pressure and humidity. CO2 sensing experiments show that present sensing setup, when CMUT structure is functionalized by thin polyethyleneimine film, has the 4 Hz/ppm sensitivity.

Application of CMUT as immunosensor

The array of the CMUT sensors was fabricated by the direct bonding of the silicon membranes provided as a device layer of the SOI wafer with the oxidized and pre-patterned highly doped silicon wafer. The active surface of the sensors was coated with thin gold film. We demonstrate the detection of the formed immune complex over the CMUT surface modified by the bovine leukemia virus antigen BLV gp51. The modified CMUT surface was allowed to interact with the specific antibody anti-gp51 labeled by the horseradish peroxidase. Antibody labels were actvated after the interaction by wetting the sensor surface with tetramethylbenzidine to provide the reference quantification of the formation of the immune complex. CMUT sensor readings (resonance frequency and the resonance value of the impedance real part, “resistance”) were obtained before and after modification by the BLV gp51 and after the interaction with antig-p51. The readings were interpreted and fitted by the finite element analysis. It was determined that increase of the elasticity modulus and stress of the sensor structure caused increase of the resonance frequency and some decrease of the resonance quality (resistance value). After the immune complex is established, we observe decrease of the resonance frequency by 4% on average from the initial value. Finite element analysis model fitting to the experimental results revealed the mass loading function of the CMUT structure in the presence of increased elasticity of the proteins.

Resonant gravimetric immunosensing based on capacitive micromachined ultrasound transducers

Interdigitally arranged and integrated with the polymer microchannels capacitive micromachined ultrasound transducers (CMUT) were designed, fabricated and tested for transverse waves, preferably Scholte type waves, excitation and receive. CMUTs were used for verification of the finite element model dedicated to predict the ability of sensing the elasticity of tethered phospholipid bilayers in liquid environment. Also, the sensitivity of the transducer and microchannel assembly to the liquid properties was tested while recording in the real time the amplitude of the received Scholte type transverse wave. Mixtures of isopropyl alcohol (IPA) and water in fractions of 10:1, 20:1 and 50:1 was used for this test. Finite element analysis predicted that considerable sensitivity of the received Scholte wave amplitude to the tethered phospholipid bilayer elasticity change from 2 to 5 GPa can be expected. The real-time sensing of the liquid mixture concentration changes revealed that even 2% water content increase (50:1 mixture case) can be sensed as 100 mV transition of the Scholte wave amplitude. Greater concentration changes caused up to 700 mV transition of the received wave amplitude.

Integrated Front End Electronics Design for Micromachined Ultrasound Transducers

Surface biofunctionalization of capacitive micromachined ultrasonic transducer (CMUT) based sensor can develop non-informative stress and elasticity, which are distorting sensor readings related with the mass of established immune complex. The prototype sensor calibration function, using polimethylmetacrylate (PMMA) films from 7 to 100 nm, was developed to relate the sensor readings with the changing mass, elasticity and stress of the film on the CMUT surface. The range of calibration in terms of mass is from 1 to 80 pg per single CMUT cell, 0 - 20 MPa in terms of stress with corresponding sensor resonance frequency and resistance readings from 10 to - 35 kHz and from 4.5 to -0.5 Ω. Antigen and antibody specific interaction sensing experiment was performed and obtained results showed that informativity of CMUT based immunosensor is much greater than expected, since most of the sensor readings were out of the calibration function, developed for PMMA, range. At the same time, immunosensing experiment demonstrated clear distinction between antigen and antibody mass, which is more than threefold.