On-chip Temperature Control Research Articles

Thermodynamic Characterization of a Highly Transparent Microfluidic Chip with Multiple On-Chip Temperature Control Units

Indium tin oxide (ITO) is a functional material with great transparency, machinability, electrical conductivity and thermo–sensitivity. Based on its excellent thermoelectric performance, we designed and fabricated a multilayer transparent microfluidic chip with multiple sets of on–chip heating, local temperature measurement and positive on–chip cooling function units. Temperature control plays a significant role in microfluidic approaches, especially in the devices that are designed for bioengineering, chemical synthesis and disease detection. The transparency of the chip contributes to achieve the real–time observation of fluid flow and optical detection. The chip consists of a temperature control layer made with an etched ITO deposited glass, a PDMS (polydimethylsiloxane) fluid layer, a PDMS cooling and flow control layer. The performances of the ITO on–chip microheaters, ITO on–chip temperature sensors and two coolants were tested and analyzed in different working conditions. The positive on–chip heating and cooling were proved to be area-specific under a large temperature–regulating range. This PDMS–ITO–glass based chip could be applied to both temporal and spatial stable temperature–regulating principles for various purposes.

Numerical Modeling of Temperature-Dependent Cell Membrane Permeability to Water Based on a Microfluidic System with Dynamic Temperature Control.

In order to describe temperature-dependent cell osmotic behaviors in a more reliable method, a novel mathematical mass transfer model coupled with dynamic temperature change has been established based on the combination of a time domain to temperature domain transformation equation and a constant temperature mass transfer model. This novel model is numerically simulated under multiple temperature changing rates and extracellular osmolarities. A microfluidic system that can achieve single-cell osmotic behavior observation and provide dynamic and swift on-chip temperature control was built and tested in this paper. Utilizing the temperature control system, the on-chip heating processes are recorded and then described as polynomial time-temperature relationships. These dynamic temperature changing profiles were performed by obtaining cell membrane properties by parameter fitting only one set of testing experimental data to the mathematical model with a constant temperature changing rate. The numerical modeling results show that predicting the osmotic cell volume change using selected dynamic temperature profiles is more suitable for studies concerning cell membrane permeability determination and cryopreservation process than tests using constant temperature changing rates.

Scalable and parallelized biochemical assays in paper devices integrated with a programmable binary valve matrix

The integration of simple fabricated paper devices with a multiplexing fluid control technology are the keys for extending traditional microfluidic applications to paper-based devices. However, paper devices to date have lacked a method for addressing the integration of complex fluid manipulations. By featuring a scalable and programmable mechanical valve matrix that is actuated by push-pull solenoids, we present a paper microfluidic multiplexing technology for performing biochemical assays in a high degree of autonomy. The technology allows every channel of a paper network to be autonomously addressed and isolated while uses a minimal number of control elements, efficiently reducing its complexity. The technology is implemented in an integrated portable system including a multiplexor controller, a relay matrix, a paper device, on-chip temperature control unit and an image analyzer. Biochemical reaction signals can be acquired and automatically interpreted via a self-built mobile App. A prototype that consists of 8 independent valve lines was demonstrated, allowing multiplexed control of a paper device with 16 operating channels. After thoroughly studying the behaviour of fluid transport in the paper device using both numerical simulation and experimentations, multiplex colorimetric assays of heavy metal samples and glucose in common soft drinks and artificial saliva samples were analyzed. To the best of our knowledge, this is the first demonstration of a simple fabricated paper device integrated with a valve multiplexing technology. The scalability of this integration makes the technology ideally suited for high-throughput analysis and holds great potential for progressing large scale integration of paper microfluidics.

Exploiting phase change materials in tunable passive heating system for low-resource point-of-care diagnostics

We present a passive heating system that allows controlled and localized on-chip heating, showing a huge potential for point-of-care (POC) diagnostic applications in low-resource settings. By coupling the thermal regulation properties of organic phase change materials (PCMs) to the exothermic crystallization reaction of supercooled sodium acetate trihydrate (SAT), on-chip temperature control is achieved without requiring external power supply. This enables the performance of sensitive and specific diagnostic tests in the field, which are currently restricted to laboratory environments. The presented system consists of 3 stacked microfluidic chambers (SAT, PCM, reagent), fabricated by means of a simple layer-by-layer manufacturing method using low-cost plastics. We showed that the SAT heat source was tunable between 35 and 55 °C by varying the salt fraction in the solution. A PCM was integrated between the SAT and reagent chamber to maintain temperature constant over time. Additionally, the introduction of this thermal buffer layer, increased the system its robustness to fluctuating ambient temperatures. Moreover, to facilitate the PCM and SAT chamber design optimization, a finite element model (FEM) was built to simulate the heat generation and transfer through the chip. With the optimized PCM-SAT system, a constant temperature between 37 and 42 °C was maintained for at least 15 min at different ambient temperatures (25–35 °C), typical conditions for a recombinase polymerase amplification assay. The ability to have simple control over both the heat release from the heat source and the regulation temperature of the PCM combined with the developed FEM, makes this system flexible to a variety of isothermal assay requirements. Moreover, the low-cost and simple fabrication method makes the system compatible with most passive microfluidic technologies (i.e., paper-based and capillary microfluidics), opening up many opportunities for integrated POC platforms.

A CMOS Electrochemical Biochip With 32$\times$ 32 Three-Electrode Voltammetry Pixels

A CMOS-integrated electrochemical biochip for high-performance molecular testing is presented. The system includes an array of 32 $\times $ 32 three-electrode voltammetry pixels and on-chip temperature control between 25 and 95 °C. Each 100 $\mu \text{m}\,\times 100\,\,\mu \text{m}$ pixel includes a CMOS-compatible and chemo-stable amorphous carbon electrode transducer connected to in-pixel $\Sigma \Delta $ current detection circuitry with 280 fA rms input-referred noise (0.1–20 Hz bandwidth) and 93 dB dynamic range (DR). Array-based DNA detection assays are implemented, and successful DNA melt-analysis and real-time label-free DNA hybridization detection are reported.

Development of a microfluidic device with precise on-chip temperature control by integrated cooling and heating components for single cell-based analysis

An integrated microfluidic device with active cooling and heating systems was developed in aiming a precise and rapid temperature control in the range between 2 °C and 37 °C. The platform, which consisted of a cooling chamber, a microheater, and a temperature sensor, achieved an active feedback control of on-chip local temperature. Multiphysics simulation was conducted in the coupled modeling of heat transfer, fluid flow, and Joule heating. These modeling and simulation validated the design parameters to achieve a precise and quick control of on-chip local temperature control. The main principle of the design is to enhance the external heat transfer by utilizing micro-channel array on the chip surface and increase the sample surface versus its volume by holding the sample inside the system as an ultra-thin film. Using the precooled saturated calcium chloride aqueous solution as the coolant, and the on-chip microheater as the heating unit, the temperature was able to be precisely adjusted, and meanwhile, the temperature was sensed by a thermal sensor at the region of interest. We demonstrated an actual temperature control and manipulation of the developed microfluidic cooling/heating system. The recorded temperature data showed that the developed integrated platform offered the capability of manipulating on-chip localized temperature ranging from 2 °C to 37 °C with active cooling/heating, especially for the temperature range from 2 °C to room temperature chosen due to typical cytotoxic issues with additive cryoprotective agents (CPAs). Additionally, this device provided valuable tools for studying temperature-dependent biological and chemical processes at microscale, for example, the determination of permeability of the cell membrane to water and CPAs in cryobiology study.

The on-chip temperature compensation and temperature control research for the silicon micro-gyroscope

In this paper, the on-chip temperature compensation and temperature control research for the silicon micro-gyroscope are presented. The proposed micro-gyroscope architecture which integrates an on-chip temperature sensor and a serpentine micro-heater achieves the on-chip temperature compensation and the on-chip temperature control of the micro-gyroscope. We first analyze the thermodynamic steady-state temperature distribution and transient temperature response of micro-gyroscope structure. Then we simulate the temperature response of the micro-gyroscope structure by Ansys software. The Deep Dry Silicon on Glass process and wet etching process are combined for fabrication of the integrated micro-gyroscope structure. The signal measurement and control circuit based on the FPGA platform are implemented. The temperature coefficients of zero bias and scale factor are compensated with the integrated temperature sensor. Taking advantage of the drive mode resonant frequency as the temperature sensor, a high precision on-chip temperature control of micro-gyroscope is realized simultaneously. The on-chip temperature compensation and temperature control experiment of micro-gyroscope prototype is tested. Experimental results indicate that the temperature coefficients of the scale factor and zero bias decrease by 3.95 times and 3.49 times separately by on-chip temperature compensation, which optimizes significantly the temperature characteristics of the micro-gyroscope prototype. The control accuracy of drive-mode frequency reaches to 3.57 × 10?4 Hz (that is 0.123 ppm and the calculated temperature accuracy of 0.0067 °C) from 0 to 40 °C by the on-chip temperature control, which demonstrates an achievement of the precision on-chip temperature control for the micro-gyroscope.

The Thermal Analysis and Simulation of On-Chip Temperature Control Technology in the Micro-Gyroscope

The thermal analysis and simulation of on-chip temperature control technology in the micro-gyroscope is researched. According to the thermal dissipation mechanism, the thermal resistance model of on-chip temperature control technology is established. The equantions of the conduction thermal resistance and the radiation thermal resistance are deduced. According to the lumped parameter model, the transient thermal response of the proof mass is derived. Theoretical analysis indicates the temperatures of the micro-heater and the proof mass are respectively 136.79°C and 59.95°C in equilibrium conditions. The Ansys simulation model of on-chip temperature control gyroscope is constructed to optimize the transient thermal response and the temperature distribution in steady-state. The simulation results show that the maximum temperature of glass thin-film is about 137.2°C, the temperature of gyroscope structure is about 58.5°C and the temperature difference is within 1°C in the steady-state. In the transient response, the temperature of gyroscope structure can be stabilized in the 12.5s. The simulation results prove that the on-chip temperature technology of micro-gyroscope has an excellent temperature uniformity and rapid temperature response.

A microfluidic approach for investigating the temperature dependence of biomolecular activity with single-molecule resolution.

We present a microfluidic approach for single-molecule studies of the temperature-dependent behavior of biomolecules, using a platform that combines microfluidic sample handling, on-chip temperature control, and total internal reflection fluorescence (TIRF) microscopy of surface-immobilized biomolecules. With efficient, rapid, and uniform heating by microheaters and in situ temperature measurements within a microfluidic flowcell by micro temperature sensors, closed-loop, accurate temperature control is achieved. To demonstrate its utility, the temperature-controlled microfluidic flowcell is coupled to a prism-based TIRF microscope and is used to investigate the temperature-dependence of ribosome and transfer RNA (tRNA) structural dynamics that are required for the rapid and precise translocation of tRNAs through the ribosome during protein synthesis. Our studies reveal that the previously characterized, thermally activated transitions between two global conformational states of the pre-translocation (PRE) ribosomal complex persist at physiological temperature. In addition, the temperature-dependence of the rates of transition between these two global conformational states of the PRE complex reveal well-defined, measurable, and disproportionate effects, providing a robust experimental framework for investigating the thermodynamic activation parameters that underlie transitions across these barriers.

An Aptameric Microfluidic System for Specific Purification, Enrichment, and Mass Spectrometric Detection of Biomolecules

We present an innovative microfluidic system that accomplishes specific capture, enrichment, and isocratic elution of biomolecular analytes with coupling to label-free mass spectrometric detection. Analytes in a liquid phase are specifically captured and enriched via their affinity binding to aptamers, which are immobilized on microbeads packed inside a microchamber. Exploiting thermally induced reversible disruption of aptamer-analyte binding via on-chip temperature control with an integrated heater and temperature sensor, the captured analytes are released into the liquid phase and then isocratically eluted and transferred via a microfluidic flow gate for detection by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). The utility of the device is demonstrated using adenosine monophosphate (AMP) as a model analyte. Experimental results indicate that the device is capable of purifying and enriching the analyte from a sample mixed with nonspecific analytes and contaminated with salts. In addition, thermally induced analyte release is performed at modest temperatures (45degC), and mass spectra obtained from MALDI-MS demonstrate successful detection of AMP at concentrations as low as 10 nM following enrichment by consecutive infusion of a diluted sample.

On-chip high speed localized cooling using superlattice microrefrigerators

In this paper, we addressed heating problems in integrated circuits (ICs) and proposed a thin-film thermionic cooling solution using Si/SiGe superlattice microrefrigerators. We compared our technology with the current most common solution, thermoelectric coolers, by strengthening the advantages of its compatible fabrication process as ICs for easy integration, small footprint in the order of /spl sim/ 100/spl times/100 /spl mu/m/sup 2/, high cooling power density, 600W/cm/sup 2/ and fast transient response less than 40 /spl mu/s. The thermoreflectance imaging also demonstrated its localized cooling. All these features combined together to make these microrefrigerators a very promising application for on-chip temperature control, removing hot spots inside IC.

Integrated microfluidic systems for cell lysis, mixing/pumping and DNA amplification

The present paper reports a fully automated microfluidic system for the DNA amplification process by integrating an electroosmotic pump, an active micromixer and an on-chip temperature control system. In this DNA amplification process, the cell lysis is initially performed in a micro cell lysis reactor. Extracted DNA samples, primers and reagents are then driven electroosmotically into a mixing region where they are mixed by the active micromixer. The homogeneous mixture is then thermally cycled in a micro-PCR (polymerase chain reaction) chamber to perform DNA amplification. Experimental results show that the proposed device can successfully automate the sample pretreatment operation for DNA amplification, thereby delivering significant time and effort savings. The new microfluidic system, which facilitates cell lysis, sample driving/mixing and DNA amplification, could provide a significant contribution to ongoing efforts to miniaturize bio-analysis systems by utilizing a simple fabrication process and cheap materials.

Influence of Doping Concentration and Ambient Temperature on the Cross-Plane Seebeck Coefficient of InGaAs/InAlAs superlattices

ABSTRACTWe have developed thin film heaters/sensors that can be integrated on top of superlattice microcoolers to measure the Seebeck coefficient perpendicular to the layer. In this paper, we discuss the Seebeck coefficients of InGaAs/InAlAs superlattices grown with Molecular Beam Epitaxy (MBE) that have different doping concentrations, varying between 2e18, 4e18, and 8e18 to 3e19 cm−3. It was interesting to find out that – contrary to the behavior in bulk material – the Seebeck coefficient did not decrease monotonically with doping concentration. A preliminary theory of thermoelectric transport in superlattices in the regime of miniband formation has been developed to fit the experimental results. The miniband formation could enhance the thermoelectric power factor (Seebeck coefficient square times electrical conductivity) and thereby improve the Figure of merit, ZT. With this improvement, InGaAs/InAlAs superlattice microcooler become a promising candidate for on-chip temperature control.

A micro-integrated Peltier heat pump for localized on-chip temperature control

A thin-film Peltier heat pump was fabricated using standard semiconductor patterning and etching techniques. The device consisted of chrome–gold and bismuth telluride metallization to form the thermoelectric junctions. The device achieved a maximum heat-pumping rate of −24 μW at a current of 0.89 mA when operating in the cooling mode. These values were less than expected primarily due to excessive contact resistance at the Au–Bi2Te3 junctions of the Peltier device. Thermal isolation of the Peltier device on a 2.4 μm thick oxide bridge was used to enhance device performance. Complete etching of the silicon surrounding this oxide bridge was not possible, due to resultant damage of the bismuth telluride thin film. The silicon remaining increased thermal losses, resulting in the Peltier device lowering the temperature of the oxide bridge only 0.23 °C below ambient.