Thermal Microfluidic Devices; Design, Fabrication and Applications

This thesis investigates the thermal actuation and temperature measurement methods in microfluidic devices. We designed and fabricated microfluidic devices with various functionalities such as: bio sensing, particle counting, microscale calorimetry, and cellular temperature measurement. All of these functionalities use thermal measurement methods. When quantitative measurements are required, the label-free nature of thermal measurement methods, along with its simple readout, make it a powerful candidate for lab on a chip and bio sensing/detection applications. In this work, thermal measurement methods are used to characterize bio-samples, measure concentrations, study thermal responses, and even perform particle cytometry. However, thermal measurement methods are known for their low speed and low sensitivity characteristics, which are influenced by thermal properties of materials and structural design. On the microscale, we designed and fabricated microfluidic structures with modified thermal properties to achieve low response times and high sensitivity. To optimize our devices, we analyzed the thermal responses of the designed structures using a first order equivalent electrical circuit model. We then compared the results of the model to the fabricated device responses. To increase the functionality of our device, we used a number of temperature measurement techniques; thermal wave analysis, AC calorimetry, time of flight measurement, and the continuous recording of differential temperature. In this work, we fabricated an on-chip calorimeter with a 200 nL chamber volume and measured specific heat and thermal conductivity of water and glycerol. Also, we measured the thermal properties of the ionic liquids with the calorimeter. Moreover, we fabricated a calorimetric microfluidic biosensor to detect and measure the glucose levels of blood with concentrations of 0.05 to 0.3% wt/vol. We applied the same method to measure DNA concentration in buffer solution and a protein binding reaction. Also, we developed a method to count the number of particles passing through a micro channel while simultaneously measuring the size deference between particles by measuring changes in thermal conductivity. We fabricated a microfluidic platform to capture a single cell to measure the temperature of the cell in response to an external stimulation

A Paper-Based Calorimetric Microfluidics Platform for Bio-chemical Sensing

In this report, a paper-based micro-calorimetric biochemical detection method is presented. Calorimetric detection of biochemical reactions is demonstrated as an extension of current colorimetric and electrochemical detection mechanisms of paper-based biochemical analytical systems. Reaction and/or binding temperature of glucose/glucose oxidase, DNA/hydrogen peroxide, and biotin/streptavidin, are measured by the paper-based micro-calorimeter. Commercially available glucose calibration samples of 0.05, 0.15 and 0.3% wt/vol concentration are used for comparing the device performance with a commercially available glucose meter (electrochemical detection). The calorimetric glucose detection demonstrates a measurement error less than 2%. The calorimetric detection results of DNA concentrations from 0.9 to 7.3 mg/mL and temperature changes in biotin and streptavidin reaction are presented to demonstrate the feasibility of integrating the calorimetric detection method with paper based microfluidic devices

A Novel On-chip Three-dimensional Micromachined Calorimeter with Fully Enclosed and Suspended Thin-film Chamber for Thermal Characterization of Liquid Samples

A microfabricated calorimeter (μ-calorimeter) with an enclosed reaction chamber is presented. The 3D micromachined reaction chamber is capable of analyzing liquid samples with volume of 200 nl. The thin film low-stress silicon nitride membrane is used to reduce thermal mass of the calorimeter and increase the sensitivity of system. The μ-calorimeter has been designed to perform DC and AC calorimetry, thermal wave analysis, and differential scanning calorimetry. The μ-calorimeter fabricated with an integrated heater and a temperature sensor on opposite sides of the reaction chamber allows to perform thermal diffusivity and specific heat measurements on liquid samples with same device. Measurement results for diffusivity and heat capacitance using time delay method and thermal wave analysis are presented

A Microfluidic Device for Thermal Particle Detection

We demonstrate the use of heat to count microscopic particles. A thermal particle detector (TPD) was fabricated by combining a 500-nm-thick silicon nitride membrane containing a thin-film resistive temperature detector with a silicone elastomer microchannel. Particles with diameters of 90 and 200 μm created relative temperature changes of 0.11 and −0.44 K, respectively, as they flowed by the sensor. A first-order lumped thermal model was developed to predict the temperature changes. Multiple particles were counted in series to demonstrate the utility of the TPD as a particle counter

On-Chip Detection of Gel Transition Temperature using a Novel Micro-Thermomechanical Method

We present a new thermomechanical method and a platform to measure the phase transition temperature at microscale. A thin film metal sensor on a membrane simultaneously measures both temperature and mechanical strain of the sample during heating and cooling cycles. This thermomechanical principle of operation is described in detail. Physical hydrogel samples are prepared as a disc-shaped gels (200 μm thick and 1 mm diameter) and placed between an on-chip heater and sensor devices. The sol-gel transition temperature of gelatin solution at various concentrations, used as a model physical hydrogel, shows less than 3% deviation from in-depth rheological results. The developed thermomechanical methodology is promising for precise characterization of phase transition temperature of thermogels at microscale

A Patterned Single Layer Graphene Resistance Temperature Sensor

Micro-fabricated single-layer graphenes (SLGs) on a silicon dioxide (SiO2)/Si substrate, a silicon nitride (SiN) membrane, and a suspended architecture are presented for their use as temperature sensors. These graphene temperature sensors act as resistance temperature detectors, showing a quadratic dependence of resistance on the temperature in a range between 283 K and 303 K. The observed resistance change of the graphene temperature sensors are explained by the temperature dependent electron mobility relationship (~T−4) and electron-phonon scattering. By analyzing the transient response of the SLG temperature sensors on different substrates, it is found that the graphene sensor on the SiN membrane shows the highest sensitivity due to low thermal mass, while the sensor on SiO2/Si reveals the lowest one. Also, the graphene on the SiN membrane reveals not only the fastest response, but also better mechanical stability compared to the suspended graphene sensor. Therefore, the presented results show that the temperature sensors based on SLG with an extremely low thermal mass can be used in various applications requiring high sensitivity and fast operation

Self-powered Triboelectric MEMS Accelerometer

A self-powered triboelectric accelerometer miniaturized to the micro-scale is presented. This micro triboelectric accelerometer (MTEA) was fabricated using CMOS-compatible processes. The design followed the triboelectric nanogenerators made in meso-scale and operates in the contact-separation mode. The scaled-down, multilayer design enabled fabrication using microelectromechanical systems (MEMS) technology. The MTEA was made using an aluminum and polyimide triboelectric pair that generated charges on the contact. A square movable plate that is 2 mm x 2 mm was fabricated with 1 μm thickness. Then, the fabricated MTEA was excited by a mini-shaker at known frequencies (0.1–7 kHz) and accelerations (1–10 g), and the output was recorded. The output was 0.7 V at the resonance frequency (700 Hz). The generated voltage has a linear relationship with the acceleration with a maximum sensitivity of 70 mV/g at the 700 Hz excitation frequency

Microscale direct measurement of localized photothermal heating in tissue-mimetic hydrogels

Abstract Photothermal hyperthermia is proven to be an effective diagnostic tool for cancer therapy. The efficacy of this method directly relies on understanding the localization of the photothermal effect in the targeted region. Realizing the safe and effective concentration of nano-particles and the irradiation intensity and time requires spatiotemporal temperature monitoring during and after laser irradiation. Due to uniformities of the nanoparticle distribution and the complexities of the microenvironment, a direct temperature measurement in micro-scale is crucial for achieving precise thermal dose control. In this study, a 50 nm thin film nickel resistive temperature sensor was fabricated on a 300 nm SiN membrane to directly measure the local temperature variations of a hydrogel-GNR mixture under laser exposure with 2 mK temperature resolution. The chip-scale approach developed here is an effective tool to investigate localization of photothermal heating for hyperthermia applications for in-vitro and ex-vivo models. Considering the connection between thermal properties, porosity and the matrix stiffness in hydrogels, we present our results using the interplay between matrix stiffness of the hydrogel and its thermal properties: the stiffer the hydrogel, the higher the thermal conductivity resulting in lower photothermal heating. We measured 8.1, 7.4, and 5.6 °C temperature changes (from the room temperature, 20 °C) in hydrogel models with stiffness levels corresponding to adipose (4 kPa), muscle (13 kPa) and osteoid (30 kPa) tissues respectively by exposing them to 2 W/cm2 laser (808 nm) intensity for 150 seconds

High Signal-To-Noise Ratio Event-Driven MEMS Motion Sensing

Two solutions for improving MEMS triboelectric vibration sensors performance in contact-separation mode are reported experimen- tally and analytically. Triboelectric sensors have mostly been studied in the mesoscale. The gap variation between the electrodes induces a potential difference that represents the external vibration. Miniaturizing the device limits the sensor output because of the limited gap. This work offers a warped MEMS diaphragm constrained on its edges. The dome-shaped structure provides one order of magnitude larger displacement after contact-separation than standard designs resulting in one order of magnitude greater volt- age and signal-to-noise-ratio. Secondly, micro triboelectric sensors do not operate unless the external vibration is sufficiently forceful to initiate contact between layers. The proposed constraints on the edge of the diaphragm provide friction during periodic motion and generate charges. The combination of the warped diaphragm and boundary constraints instead of serpentine springs increases the charge density and voltage generation. The mechanical properties and electrical output are thoroughly investigated including nonlinearity, sensitivity, and signal-to-noise ratio. Sensitivity of 250 mV/g and signal-to-noise-ratio of 32 dB is provided by the pre- sented device at resonance which is very promising for event-driven motion sensors because it does not require signal conditioning and therefore simplifies the sensing circuitry