Damien Maillard
The objective of this PhD thesis is the development of a microfluidic platform for the real-time measurements of the mechanical properties of biological analytes at the single entity level.The systems developed for these purposes consist of piezoelectrically-transduced suspended microchannel resonators (SMRs). Their operation is based on the tracking of their resonance frequency when samples are flowing through the SMR, because the resonance frequency depends on the mechanical properties of the system (e.g. stiffness or mass).The structure of the SMRs is made of low-stress silicon nitride (ls-SiNx), a material offering multiple advantages (good mechanical properties, high temperature and chemical resistance, transparency, amongst others). The cross-sectional area of the fluidic channel is designed to accommodate the detection of red blood cells and circulating tumor cells, biological entities that are known to have mechanical properties correlating with various pathologies, including cancer. The length of the devices ranges from 50 to 1000 ÎŒm, covering multiple orders of magnitudes in resonance frequencies. Each chip consists of a microfluidic network comprising 2 to 4 SMRs of different lengths to enable measurements of the same analyte with different devices.The fabrication relies on a 7-mask process flow. The manufacture of the channels requires two electron-beam lithographies, multiple depositions of ls-SiNx, as well as a polysilicon sacrificial layer. The piezoelectric (PZE) stack is fabricated on top of the flat channel surface and consists of platinum electrodes and an aluminum nitride active layer. Fluidic accesses are then etched from the backside of the wafer before the resonators are released on the front.The chips fabricated can be assembled in a dedicated experimental setup. A fluidic connector along with the implementation of o-rings ensure leak-free delivery of fluidic samples from a pressured-controlled pump to the SMR chip. The electrical transduction is achieved with a PCB that is connected to a lock-in amplifier. A vacuum chamber sealed with o-rings is pumped and guarantees operation of SMRs at low pressure, while temperature control is achieved with a Peltier module and a thermistor.Multiple characterization steps are performed to assess the performance of the devices from a piezoelectric standpoint both in static and dynamic mode. The frequency stability of empty and filled SMRs is also studied through measurements of the Allan deviation, an established metrics for resonators. Measurements with a 200-ÎŒm-long SMR demonstrate a theoretical buoyant mass resolution of 150 ag (at an integration time of 400 ms), a performance close to the state of the art for devices of similar dimensions.The SMRs are also evaluated as density sensors and show that a theoretical density resolution close to 0.5 g/m3 is achievable, which is an order of magnitude better than commercial devices. It is also demonstrated that the piezoelectric nature of the transduction allows to estimate how the resonators are affected by the heat absorption inherent to the operation of an optical detection system such as a Laser Doppler Vibrometer. Finally, SMRs enable the measurement of the buoyant mass of a population of bacteria isolated from lake water at the single analyte level. To the best of our knowledge, this is the first characterization of the mechanical properties of single entities with piezoelectric suspended microchannel resonators.
EPFL2022
