Ioana Voiculescu

Acoustic wave based MEMS devices for biosensing applications

This paper presents a review of acoustic-wave based MEMS devices that offer a promising technology platform for the development of sensitive, portable, real-time biosensors. MEMS fabrication of acoustic wave based biosensors enables device miniaturization, power consumption reduction and integration with electronic circuits. For biological applications, the biosensors are integrated in a microfluidic system and the sensing area is coated with a biospecific layer. When a bioanalyte interacts with the sensing layer, mass and viscosity variations of the biospecific layer can be detected by monitoring changes in the acoustic wave properties such as velocity, attenuation, resonant frequency and delay time. Few types of acoustic wave devices could be integrated in microfluidic systems without significant degradation of the quality factor. The acoustic wave based MEMS devices reported in the literature as biosensors and presented in this review are film bulk acoustic wave resonators (FBAR), surface acoustic waves (SAW) resonators and SAW delay lines. Different approaches to the realization of FBARs, SAW resonators and SAW delay lines for various biochemical applications are presented. Methods of integration of the acoustic wave MEMS devices in the microfluidic systems and functionalization strategies will be also discussed.

Evaluation of bimaterial cantilever beam for heat sensing at atmospheric pressure

The bimaterial cantilever beam is an important basic structure of microelectromechanical system thermal devices. The research described in this paper is a study of the deflection of the bimaterial cantilever beam operated in the air and irradiated with a laser beam at the free end. The bimaterial cantilever beam is a composite structure formed by layers of silicon nitride and gold. The temperature variations produce the deflection of the cantilever beam end due to different values of the thermal expansion coefficients of silicon nitride and gold. The deflection was experimentally measured in vacuum and atmospheric pressure when a laser beam was irradiated at the free end. A formula for the calculation of the deflection as a function of incident power applied at the free end of the cantilever beam operated in air was also demonstrated. The predicted values of the deflection calculated using this formula and the experimental values of the deflection were compared, and the results were in good agreement. A systematic investigation of the cantilever beam deflection in vacuum and atmospheric pressure as a function of the heat applied at the free end is important for chemical and biological applications.

A novel cell-based hybrid acoustic wave biosensor with impedimetric sensing capabilities

A novel multiparametric biosensor system based on living cells will be presented. The biosensor system includes two biosensing techniques on a single device: resonant frequency measurements and electric cell-substrate impedance sensing (ECIS). The multiparametric sensor system is based on the innovative use of the upper electrode of a quartz crystal microbalance (QCM) resonator as working electrode for the ECIS technique. The QCM acoustic wave sensor consists of a thin AT-cut quartz substrate with two gold electrodes on opposite sides. For integration of the QCM with the ECIS technique a semicircular counter electrode was fabricated near the upper electrode on the same side of the quartz crystal. Bovine aortic endothelial live cells (BAECs) were successfully cultured on this hybrid biosensor. Finite element modeling of the bulk acoustic wave resonator using COMSOL simulations was performed. Simultaneous gravimetric and impedimetric measurements performed over a period of time on the same cell culture were conducted to validate the devices sensitivity. The time necessary for the BAEC cells to attach and form a compact monolayer on the biosensor was 35∼45 minutes for 1.5 × 104 cells/cm2 BAECs; 60 minutes for 2.0 × 104 cells/cm2 BAECs; 70 minutes for 3.0 × 104 cells/cm2 BAECs; and 100 minutes for 5.0 × 104 cells/cm2 BAECs. It was demonstrated that this time is the same for both gravimetric and impedimetric measurements. This hybrid biosensor will be employed in the future for water toxicity detection.

Electrical cell-substrate impedance sensing (ECIS) based biosensor for characterization of DF-1 cells

Electric cell-substrate impedance sensing (ECIS) method can be used as a valuable tool for real time monitoring of cell behavior such as attachment, mobility, and growth. Changes in impedance of the cells due to growth and attachment can be modeled as an equivalent circuit consisting of resistors and capacitors of both the cell culture media and the cells. In this work, a biosensor which measures the impedance in DF-1 cells (derived from chicken embroyonic fibroblasts and CEF cells) are presented. The biosensor consists of a Teflon cell holder and two gold electrodes. Experimental measurements were conducted using DF-1 cells cultured in DMEM media. Two different experiments were conducted namely; the control experiment (holder contains only DMEM media) and the cell experiment (holder contains both DMEM media and cells). The biosensor was placed in an incubator with optimum settings for cell growth. Impedance measurements were sampled at six hour intervals. Based on these measurements the resistance and capacitance change due to the growth of the DF-1 cells were calculated. It was observed that significant change in resistance and capacitance values occurs in the first six hours, where cell growth and attachment is most active. After this period of time, the cells become confluent and capacitance values become saturated.

Characterization of endothelial cells using electrochemical impedance spectroscopy

In this paper we report on the electrical impedance spectroscopy characterization of endothelial cell lines (RFPEC). For electrical cell-substrate impedance sensing (ECIS) of the endothelial cells a commercially available eight-well cell culture impedance array (ECIS-8W1E) was used. The impedance measurements were recorded with cell culture medium (without cells) and with endothelial cell layer in the culture medium over a frequency range from 100 Hz to 100 kHz. The impedance measurements were compared to the equivalent circuit model. The impedance measurements of endothelia cells were also simulated using COMSOL Multiphysics™, a commercially available modeling package.

Printed circuit board cultureware for analysis of colorectal carcinoma cells using impedance spectroscopy

In this paper we report on the fabrication and testing of an impedance biosensor which is fabricated on a printed circuit board. The sensors interdigitated electrodes were designed using COMSOL Multiphysics™. To yield inexpensive, easily manufactured sensors, the devices were fabricated on a glass-reinforced epoxy laminate (FR4) printed circuit board (PCB). An eight-well chamber slide was glued on the PCB sensor to form the cultureware. To facilitate cell attachment to the electrodes, cell substrate was coated on the electrodes. Two different cell substrates gelatin and polyaniline were coated on different devices to evaluate the effectiveness of the cell substrate. The fabricated PCB sensor was tested using human colorectal carcinoma cells (HCT116). The impedance measurements were recorded with cell culture medium (without cells) and with colorectal cancer cells in the culture medium over a frequency range from 100 Hz to 10 MHz. The impedance measurements were compared to the equivalent circuit model.

Acoustic Wave Based MEMS Devices, Development and Applications

Acoustic waves based MEMS devices offer a promising technology platform for a wide range of applications due to their high sensitivity and the capability to operate wirelessly. These devices utilize acoustic waves propagating through or on the surface of a piezoelectric material. An acoustic wave device typically consists of two layers, metal transducers on top of piezoelectric substrate or thin films. The piezoelectric material has inherent capabilities of generating acoustic waves related to the input electrical sinusoidal signals placed on the transducers. Using this characteristic, different transducer designs can be placed on top of the piezoelectric material to create acoustic wave based filters, resonators or sensors. Historically, acoustic wave devices have been and are still widely used in telecommunications industry, primarily in mobile cell phones and base stations. Surface Acoustic Wave (SAW) devices are capable of performing powerful signal processing and have been successfully functioning as filters, resonators and duplexers for the past 60 years. Although SAW devices are technological mature and have served the telecommunication industry for several decades, these devices are typically fabricated on piezoelectric substrates and are packaged as discrete components. Considering the wide flexibility and capabilities of the SAW device to form filters, resonators there has been motivation to integrate such devices on silicon substrates as demonstrated in (Nordin et al., 2007; M. J. Vellekoop et al., 1987; Visser et al., 1989). One such example is illustrated in (Nordin et al., 2007) where a CMOS SAW resonator was fabricated using 0.6 m AMIs CMOS technology process with additional MEMS post-processing. The traditional SAW structure of having the piezoelectric at the bottom was inverted. Instead, the IDTs were cleverly manufactured using standard complementary-metal-oxide-semiconductor (CMOS) process and the piezoelectric layer was placed on the top. Active circuitry can be placed adjacent to the CMOS resonator and can be connected using the integrated metal layers. A SAW device can also be designed to have a long propagation path between the input and output transducer. The propagating acoustic waves will then be very sensitive to ambient changes, allowing the device to act as a sensor. Any variations to the characteristics of the propagation path affect the velocity or amplitude of the wave. Important application for acoustic wave devices as sensors include torque and tire pressure sensors (Cullen et al., 1980; Cullen et al., 1975; Pohl et al., 1997), gas sensors (Levit et al., 2002; Nakamoto et al., 1996; Staples, 1999; Wohltjen et al., 1979), biosensors for medical applications (Andle et al., 1995; Ballantine et al., 1996; Cavic et al., 1999; Janshoff et al., 2000), and industrial and commercial applications (vapor, humidity, temperature, and mass sensors) (Bowers et al., 1991; Cheeke et al., 1996; Smith, 2001; N. J. Vellekoop et al., 1999; Vetelino et al., 1996; Weld et al., 1999). In recent years, the interest in the development of highly sensitive acoustic wave devices as biosensor platforms has grown. For biological applications the acoustic wave device is integrated in a microfluidic system and the sensing area is coated with a biospecific layer. When a bioanalyte interacts with this sensing layer, physical, chemical, and/or biochemical changes are produced. Typically, mass and viscosity changes of the biospecific layer can be detected by analyzing changes in the acoustic wave properties such as velocity, attenuation and resonant frequency of the sensor. An important advantage of the acoustic wave biosensors is simple electronic readout that characterizes these sensors. The measurement of the resonant frequency or time delay can be performed with high degree of precision using conventional electronics. This chapter is focused on two important applications of the acoustic-wave based MEMS devices; (1) biosensors and (2) telecommunications. For biological applications these devices are integrated in a microfluidic system and the sensing area is coated with a biospecific layer. When a bioanalyte interacts with this sensing layer, physical, chemical, and/or biochemical changes are produced. Typically, mass and viscosity changes of the biospecific layer can be detected by analyzing changes in the acoustic wave properties such as velocity, attenuation and resonant frequency of the sensor. An important advantage of the acoustic wave biosensors is simple electronic readout that characterizes these sensors. The measurement of the resonant frequency and time delay can be performed with high degree of precision using conventional electronics. Only few types of acoustic wave devices could be integrated in microfluidic systems without significant degradation of the quality factor. The acoustic wave based MEMS devices reported in the literature as biosensors are film bulk acoustic wave resonators (FBAR) and surface acoustic waves (SAW) resonators and SAW delay lines. Different approaches to the realization of FBARs and SAW resonators and SAW delay lines used for various biochemical applications are presented. Next, acoustic wave MEMS devices used in telecommunications applications are presented. Telecommunication devices have different requirements compared to sensors, where acoustic wave devices operating as a filter or resonator are expected to operate at high frequencies (GHz), have high quality factors and low insertion losses. Traditionally, SAW devices have been widely used in the telecommunications industry, however with advancement in lithographic techniques, FBARs are rapidly gaining popularity. FBARs have the advantage of meeting the stringent requirement of telecommunication industry of having Qs in the 10,000 range and silicon compatibility.

On-chip hotplate for temperature control of CMOS SAW resonators

Due to the sensitivity of the piezoelectric layer in surface acoustic wave (SAW) resonators to temperature, a method of achieving device stability as a function of temperature is required. This work presents the design, modeling and characterization of integrated dual-serpentine polysilicon resistors as a method of temperature control for CMOS SAW resonators. The design employs the oven control temperature stabilization scheme where the devicepsilas temperature is elevated to higher than Tmax to maintain constant device temperature. The efficiency of the polysilicon resistor as a heating element was verified through a 1-D partial differential equation model, 3-D CoventorWarereg finite element simulations and measurements using Compixreg thermal camera. To verify that the on-chip hotplate is effective as a temperature control method, both DC and RF measurements of the heater together with the resonator were conducted. Experimental results have indicated that the TCF of the CMOS SAW resonator of -97.2 ppm/degC has been reduced to -23.19 ppm/degC when heated to 56degC.

Screen Printed Impedance Biosensor for Cytotoxicity Studies of Lung Carcinoma Cells

Electrical Cell-Substrate Impedance Sensing is a powerful tool for monitoring real time cells properties such as adhesion, mobility and cytotoxicity. In this study, a silver/silver chloride screen-printed impedance biosensor was developed to characterize A549 lung carcinoma cells growth in the presence of collagen I, Bovine. Collagen acts as an extracellular matrix (ECM) for A549 and promotes cell attachment. The sensor was incorporated with a culture well which was fabricated from polydimethylsiloxane (PDMS). A549 cells were cultured in the chambers and impedance measurements were taken at 12 hours intervals for 120 hours. Cell Index (CI) were calculated from the impedance data and plotted in comparison with growth profile of the cells in T-flasks for validation of the sensor’s functionality. A549 cells were also treated with anti-tumor drug; Paclitaxel and its response were monitored over 5 days. Experimental results show significant change in CI during growth and death after exposure to Taxol, indicating that tumor growth was inhibited in the presence of Taxol.

Research Lead Student Projects on Multi-Disciplinary Optomechatronics with Applications in Biomedical Imaging

The education side of an optomechatronics consortium of academic and industrial partners is presented. The consortium covers a variety of disciplines including mechanical design, theory of mechanisms, mechatronics, as well as optical engineering with applications in specific biomedical fields, such as dentistry and gastroenterology. The five teams involved in the project compound senior and young researchers, including graduate and undergraduate students). The contribution of each partner is presented, with examples of specific methodology in conducting student projects on subjects inspired by research.