Katia Grenier

Integrated Broadband Microwave and Microfluidic Sensor Dedicated to Bioengineering

This paper presents an innovative high-frequency- based biosensor, which combines both microwave detection and microfluidic network for time-efficient and accurate biological analysis. It is composed of a coplanar waveguide with a microfluidic channel placed on top. With the help of an appropriate de-embedding technique and modeling of the measurements, the relative effective permittivity of human umbilical vein endothelial cells has been evaluated successfully. Furthermore, experiments have been performed with the sensor on various cell concentrations in suspension, which validates its use in bioengineering applications such as cell quantification and counting in solution. This sensor requires no direct contact or use of labels on the cells, contrary to other usual types of biosensors (optical, mechanical or dc/low-frequency-detection-based ones).

A Microwave and Microfluidic Planar Resonator for Efficient and Accurate Complex Permittivity Characterization of Aqueous Solutions

A microwave resonator is presented as a microfabricated sensor dedicated to liquid characterization with perspectives for chemistry and biology. The nanolitter range aqueous solution under investigation is located on top of the planar resonator thanks to a microfluidic channel compatible with a future lab-on-a-chip integration. The interaction between the electric field and the liquid translates into a predictable relationship between electrical characteristics of the resonator (resonant frequency and associated insertion loss) and the complex permittivity of the fluid (real and imaginary parts). A prototype of the resonator has been fabricated and evaluated with de-ionized water/ethanol mixtures with ethanol volume fraction ranging from 0% to 20%. Good agreement has been reached between theoretical and measured electrical parameters of the resonator. The discrepancy on the resonant frequency is estimated to 0.5%, whereas the one on the associated transmission coefficient is lower than 1%. This translates into a maximum relative error on the real and imaginary part of the predicted relative permittivity of less than 6.5% and 4%, respectively, validating the principle of this accurate permittivity characterization methodology.

Reliability modeling of capacitive RF MEMS

The kinetic of dielectric charging in capacitive RF microelectromechanical systems (RF MEMS) is investigated using an original method of stress and monitoring. This effect is investigated through a new parameter: the shift rate of the actuation voltages. We demonstrate that this lifetime parameter has to be considered as a function of the applied voltage normalized by the contact quality between the bridge and the dielectric. We also demonstrate that this phenomenon is related to Frenkel-Poole conduction, which takes place into the dielectric. We finally propose a model that describes the dielectric charging kinetic in capacitive RF MEMS. This model is used to extract a figure-of-merit of capacitive switches lifetime.

Micromachined Loop Antennas on Low Resistivity Silicon Substrates

The integration of K-band (20-40 GHz) full wavelength square wire- and slot-loop antennas on low resistivity (11-70 Omegacm) silicon substrates is addressed. By the use of polymer or silicon oxide/nitride membranes to support the slot or wire loop over micromachined trenches the efficiency of the antennas is enhanced while the majority of the bulk silicon within the aperture of the antenna is preserved to enable the integration of active devices. A 3.6times3.6 mm2 large slot loop antenna chip with 200 mum micromachined trench width yields 1.5 dBi gain at 29.5 GHz, while 1.0 dBi gain is obtained at 24 GHz for a wire loop antenna on a 4.5times4.5 mm2 large chip with 360 mum wide trenches

Recent Advances in Microwave-Based Dielectric Spectroscopy at the Cellular Level for Cancer Investigations

Cancer remains a leading cause of death in the world. To overcome this problem, it is necessary to develop new analysis tools, in complementarity to existing ones, to enable the early diagnostic of the diseases, personalized treatment, and further fundamental cancer mechanisms understanding. In this context, microwave-based and millimeter-wave-based dielectric spectroscopy performed at the cellular and molecular levels is progressively emerging, as it permits the non-invasive and real-time probing of cells in their culture biological medium. The recent advances of this topic are given in this paper with a specific highlight of its various assets.

Accurate Nanoliter Liquid Characterization Up to 40 GHz for Biomedical Applications: Toward Noninvasive Living Cells Monitoring

This paper demonstrates an accurate liquid sensing technique, from 40 MHz to 40 GHz, which is suitable for the detection and quantification of very small contents of molecules, proteins, and for the noninvasive and contactless microwave investigation of living cells in their culture medium. The sensor is based on an interdigitated capacitor (IDC) with a microfluidic channel to confine the nanoliter-range liquid and is integrated with microtechnologies to be fully compatible with a massive parallelization at low cost. Both alcohol and biological aqueous solutions are precisely characterized, identified, and quantified in terms of capacitance and conductances contrasts with respect to pure de-ionized water. Mixtures from 20% down to 1% of ethanol in water exhibit large capacitances values of 110 and 7 fF at 11 GHz, respectively. Based on the high accuracy of such characterizations, the detection of very small traces of ethanol (down to 100 ppm) can be envisioned. As far as biomedical applications are targeted, we also demonstrate the potential of fetal bovine serum detection in aqueous solution down to 5% v/v. Finally, the sensor is evaluated with living B lymphoma cells suspension in their traditional biological medium. The in-liquid microwave measurement of less than 20 living cells is successfully performed and corresponds to a capacitance contrast of 5 fF at 3 GHz relative to the reference bio-medium. For low cells concentration, the sensor response is proportional to the number of cells on the IDC, which permits to envision cells quantification and proliferation monitoring with this microwave sensing technique.

Experimental determination of microwave attenuation and electrical permittivity of double-walled carbon nanotubes

The attenuation and the electrical permittivity of the double-walled carbon nanotubes (DWCNTs) were determined in the frequency range of 1–65GHz. A micromachined coplanar waveguide transmission line supported on a Si membrane with a thickness of 1.4μm was filled with a mixture of DWCNTs. The propagation constants were then determined from the S parameter measurements. The DWCNTs mixture behaves like a dielectric in the range of 1–65GHz with moderate losses and an abrupt change of the effective permittivity that is very useful for gas sensor detection.

Failure predictive model of capacitive RF-MEMS

This paper reports on the investigation of the failure mechanism in capacitive RF-MEMS through an efficient analysis methodology. We demonstrate that the physical origin of the dielectric charging is the leakage current through the RF-MEMS dielectric. To monitor the kinetic of this failure phenomenon, we introduce a useful parameter, which corresponds to the shift rate of the actuation voltages (SRAV) and an appropriate reliability-driven electrical stress parameter, which takes the contact quality between the bridge and the dielectric into account. We finally propose a figure of merit, derived from a predictive model, which quantifies the capacitive RF MEMS reliability and open the door to the prediction of lifetime as well as its optimization and/or acceleration for testing.

Microwave biosensor dedicated to the dielectric spectroscopy of a single alive biological cell in its culture medium

This paper presents a biosensor dedicated to the dielectric spectroscopy of a single and living biological cell in its liquid culture medium in the micro and millimeter wave ranges. This detector works in the near field and involves a capacitive gap to perform the electromagnetic sensing, while a microfluidic system has been developed and adapted to the RF circuit to precisely localize the single biological cell under study. Both capacitive and conductive contrasts of a living biological cell measured in its culture medium are accessible. A living B lymphoma cell has then been measured from 40 MHz up to 40 GHz, with a measured capacitive contrast of the order of several hundreds of attofarads.

Mechanical Stress Impairs Mitosis Progression in Multi-Cellular Tumor Spheroids

Growing solid tumors are subjected to mechanical stress that influences their growth rate and development. However, little is known about its effects on tumor cell biology. To explore this issue, we investigated the impact of mechanical confinement on cell proliferation in MultiCellular Tumor Spheroids (MCTS), a 3D culture model that recapitulates the microenvironment, proliferative gradient, and cell-cell interactions of a tumor. Dedicated polydimethylsiloxane (PDMS) microdevices were designed to spatially restrict MCTS growth. In this confined environment, spheroids are likely to experience mechanical stress as indicated by their modified cell morphology and density and by their relaxation upon removal from the microdevice. We show that the proliferation gradient within mechanically confined spheroids is different in comparison to MCTS grown in suspension. Furthermore, we demonstrate that a population of cells within the body of mechanically confined MCTS is arrested at mitosis. Cell morphology analysis reveals that this mitotic arrest is not caused by impaired cell rounding, but rather that confinement negatively affects bipolar spindle assembly. All together these results suggest that mechanical stress induced by progressive confinement of growing spheroids could impair mitotic progression. This study paves the way to future research to better understand the tumor cell response to mechanical cues similar to those encountered during in vivo tumor development.