Integrated single-walled carbon nanotube/microfluidic devices for the study of the sensing mechanism of nanotube sensors

A method to fabricate integrated single-walled carbon nanotube/microfluidic devices was developed. This simple process could be used to directly prepare nanotube thin film transistors within the microfluidic channel and to register SWNT devices with the microfludic channel without the need of an additional alignment step. The microfluidic device was designed to have several inlets that deliver multiple liquid flows to a single main channel. The location and width of each flow in the main channel could be controlled by the relative flow rates. This capability enabled us to study the effect of the location and the coverage area of the liquid flow that contained charged molecules on the conduction of the nanotube devices, providing important information on the sensing mechanism of carbon nanotube sensors. The results showed that in a sensor based on a nanotube thin film field effect transistor, the sensing signal came from target molecules absorbed on or around the nanotubes. The effect from adsorption on metal electrodes was weak.     

Integrated ionic liquid-based electrofluidic circuits for pressure sensing within polydimethylsiloxane microfluidic systems

This paper reports a novel pressure sensor with an electrical readout based on electrofluidic circuits constructed by ionic liquid (IL)-filled microfluidic channels. The developed pressure sensor can be seamlessly fabricated into polydimethylsiloxane (PDMS) microfluidic systems using the well-developed multilayer soft lithography (MSL) technique without additional assembly or sophisticated cleanroom microfabrication processes. Therefore, the device can be easily scaled up and is fully disposable. The pressure sensing is achieved by measuring the pressure-induced electrical resistance variation of the constructed electrofluidic resistor. In addition, an electrofluidic Wheatstone bridge circuit is designed for accurate and stable resistance measurements. The pressure sensor is characterized using pressurized nitrogen gas and various liquids which flow into the microfluidic channels. The experimental results demonstrate the great long-term stability (more than a week), temperature stability (up to 100 °C), and linear characteristics of the developed pressure sensing scheme. Consequently, the integrated microfluidic pressure sensor developed in this paper is promising for better monitoring and for characterizing the flow conditions and liquid properties inside the PDMS microfluidic systems in an easier manner for various lab on a chip applications.     

Configuration and optimization of semiconductor gas sensors as gas chromatographic detectors

A tin oxide, gas-sensitive semiconductor sensor was configured as a gas chromatographic detector and its performance was optimized. Two sensor housings were compared but little difference was found in performance. The flow rate and temperature of the column and the internal heater voltage of the sensor affected both the sensitivity and peak shape. The temperature of the sensor surface was the most critical parameter. Optimal conditions for the gas chromatographic detection of a mixture of alkanes (C₁–C₅) and hydrogen were identified by using the simplex technique. The detection limit for hydrogen was improved by a factor of five to 20 ppb (v/v), illustrating the value of optimization and the excellent sensitivity of the detector. It is concluded that semiconductor gas sensors offer significant advantages as gas chromatographic detectors for the determination of reducing gases.     

Novel pressure stable thermoelectric flow sensor in non-steady state operation mode for inline process analysis in micro reactors

In this contribution results of the non-steady state operation of a novel pressure stable thermoelectric flow sensor chip for the inline chemical process analysis in micro reactors are presented. The sensor chip consists of a heater in between two thermopiles on a novel perforated membrane, thus liquid flows on both sides. Compared to the conventional constant overtemperature/current operation the heater is now operated in non-steady state/pulsed mode and step responses of both thermopiles are evaluated. Based on our results the non-steady operation of the heater leads to a better discrimination between thermal conductivity and heat capacity of the liquid.     

Photobleaching-based flow measurement in a commercial capillary electrophoresis chip instrument

For microfluidic analytical instruments, a facile, fast, and accurate instrument test is highly demanded. The test includes the quantitative verification of the relationship between pressure drop and flow velocity for the hydrodynamic pump, between the electric voltage and electroosmotic flow (EOF) for the high-voltage supply, and the chip quality. The key point for the test is the measurement of the flow velocity. However, most currently available velocimetries cannot be directly used without any instrumental modification or adding extra instruments. We applied a recently developed Laser Induced Fluorescence Photobleaching Anemometer (LIFPA) for the instrument test through measuring fluid flow velocity in a microfluidic instrument with optical measurement without any modification and extra instrument. We have successfully used the method to test Caliper HTS 250 System from Caliper Life Sciences (Hopkinton, MA) with its own light source and detector. The experimental result demonstrates that this single-point method of measuring flow velocity can be easily used for accurate test of a microfluidic instrument in less than 10 min at extremely low cost without any modification and extra instrument.     

A large volume, portable, real-time PCR reactor

A point-of-care, diagnostic system incorporating a portable thermal cycler and a compact fluorescent detector for real-time, polymerase chain reaction (PCR) on disposable, plastic microfluidic reactors with relatively large reaction volume (ranging from 10 μL to 100 μL) is described. To maintain temperature uniformity and a relatively fast temperature ramping rate, the system utilizes double-sided heater that features a master, thermoelectric element and a thermal waveguide connected to a second thermoelectric element. The waveguide has an aperture for optical coupling between a miniature, fluorescent reader and the PCR reaction chamber. The temperature control is accomplished with a modified, feedforward, variable structural proportional-integral-derivative controller. The temperature of the liquid in the reaction chamber tracks the set-point temperature with an accuracy of ± 0.1 °C. The transition times from one temperature to another are minimized with controllable overshoots (< 2 °C) and undershoots (< 5 °C). The disposable, single-use PCR chip can be quickly inserted into a thermal cycler/reader unit for point-of-care diagnostics applications. The large reaction chamber allows convenient pre-storing of dried, paraffin-encapsulated PCR reagents (polymerase, primers, dNTPs, dyes, and buffers) in the PCR chamber. The reagents are reconstituted "just in time" by heating during the PCR process. The system was tested with viral and bacterial nucleic acid targets.     

A constant voltage constant current wheatstone bridge configuration

For many measurement applications a Wheatstone bridge configuration can be used to measure physical quantities, such as pressure, force or velocity. Offset behaviour plays a vital role in the overall accuracy. Often, ambient temperature changes cause undesired changes in parameters that are supposed to be constant.In this paper, an integrated silicon double bridge configuration is presented using a sophisticated sensor biasing principle in one bridge, whilst simultaneously maintaining the supply current and the supply voltage constant.Sensor biasing is achieved by using thermal feedback between the two bridges. Applying this principle will reduce drift to a large extent and may even make laser or any other trimming procedure obsolete. Moreover, full integration of the sensor and the signal processing parts, consisting of complicated highly accurate analogue circuits, is possible due to the constant parameters provided. To demonstrate the utility of this concept, an integrated silicon anemometer is described.     

Description of the response of a fiber optic velocity sensor applied to capillary gas chromatography

This paper explores the response of a novel fiber optics sensor allowing real-time determination of the migration rate of vapor zones in capillary gas chromatography. The sensitivity is related to the gradient of the vapor zone distribution in the capillary and it is highest when vapor zones show steep variations in concentration. The expected linearity between the height of the velocity peaks and the response of a thermal conductivity detector is demonstrated experimentally. The sensor can be used to infer an approximate value of the analyte diffusion coefficient from the time response. Finally, the time evolution of the envelope of the optical signal is explained with experimental evidences.     

Performing microchannel temperature cycling reactions using reciprocating reagent shuttling along a radial temperature gradient

This study develops a novel temperature cycling strategy for executing temperature cycling reactions in laser-etched poly(methylmethacrylate) (PMMA) microfluidic chips. The developed microfluidic chip is circular in shape and is clamped in contact with a circular ITO heater chip of an equivalent diameter. Both chips are fabricated using an economic and versatile laser scribing process. Using this arrangement, a self-sustained radial temperature gradient is generated within the microfluidic chip without the need to thermally isolate the different temperature zones. This study demonstrates the temperature cycling capabilities of the reported microfluidic device by a polymerase chain reaction (PCR) process using ribulose 1,5-bisphosphate carboxylase large subunit (rbcL) gene as a template. The temperature ramping rate of the sample inside the microchannel is determined from the spectral change of a thermochromic liquid crystal (TLC) solution pumped into the channel. The present results confirm that a rapid thermal cycling effect is achieved despite the low thermal conductivity of the PMMA substrate. Using IR thermometry, it is found that the radial temperature gradient of the chip is approximately 2 degrees C mm(-1). The simple system presented in this study has considerable potential for miniaturizing complex integrated reactions requiring different cycling parameters.     

Noninvasive fluid flow measurements in microfluidic channels with backscatter interferometry

The ability to measure fluid velocity within picoliter volumes or on-chip noninvasively, is important toward fully realizing the potential of microfluidics and micrototal analysis systems, particularly in applications such as micro-high-performance liquid chromatography (HPLC) or in metering mixing where the flow rate must be quantified. Additionally, these measurements need to be performed directly on moving fluids in a noninvasive fashion. We presented here the proof of principle experiments showing nonintrusive fluid flow measurements can be accomplished on-chip using a pump and probe configuration with backscattering interferometry. The on-chip interferometric backscatter detector (OCIBD) is based on a fiber-coupled HeNe laser that illuminates a portion of an isotropically etched 40 microm radius channel and a position sensitive transducer to measure fringe pattern shifts. An infrared laser with a mechanical shutter is used to heat a section of a flowing volume and the resulting refractive index (RI) change is detected with the OCIBD downstream as a time-dependent RI perturbation. Fluid velocity is quantified as changes in the phase difference between the shutter signal and the OCIBD detected signal in the Fourier domain. The experiments are performed in the range of 3-6 microL/h with 3sigma detection limits determined to be 0.127 nL/s. Additionally, the RI response of the system is calibrated using temperature changes as well as glycerol solutions.     

Patterning, integration and characterisation of polymer optical oxygen sensors for microfluidic devices

This paper describes a process for the layer-by-layer fabrication and integration of luminescent dye-based optical oxygen sensors into microfluidic devices. Application of oxygen-sensitive platinum(ii) octaethylporphyrin ketone fluorescent dye dissolved in polystyrene onto glass substrates by spin-coating was studied. Soft lithography with polydimethylsiloxane (PDMS) stamps and reactive ion etching in oxygen plasma were used to produce sensor patterns with a minimum feature size of 25 microm. Sensors patterns were integrated into a PDMS microfluidic device by plasma bonding. No degradation of the sensor response as a result of the lithography and pattern-transfer processes was detected. Gaseous and dissolved oxygen (DO) detection was characterised using fluorescence microscopy. The intensity signal ratio of the sensor films was found to increase almost two-fold from 3.6 to 6.8 by reducing film thickness from 1.3 microm to 0.6 microm. Calibration of DO measurement showed linear Stern-Volmer behaviour that was constant for flow rates from 0.5 to 2 mL min(-1). The calibrated sensors were subsequently used to demonstrate laterally resolved detection of oxygen inside a microfluidic channel. The fabrication process provides a novel, easy to use method for the repeatable integration of optical oxygen sensors into cell-culture and lab-on-a-chip devices.     

A universal temperature controlled membrane interface for the analysis of volatile and semi-volatile organic compounds

A universal temperature controlled membrane interface (TCMI) has been constructed for hollow-fibre membranes. The membrane temperature is controllable in the range -70 to 250 degrees C using an electric heater and a flow of cooled nitrogen or helium gas. Volatile and semi-volatile organic compounds may be detected either by continuous diffusion across the membrane or by in-membrane pre-concentration followed by thermal desorption into the detector. The TCMI interface is demonstrated in combination with mass spectrometry and GC-MS, for the determination of VOCs and SVOCs in aqueous and air samples and for the on-line monitoring of a bioreactor.     

Hot embossing and thermal bonding of poly(methyl methacrylate) microfluidic chips using positive temperature coefficient ceramic heater

As a self-regulating heating device, positive temperature coefficient ceramic heater was employed for hot embossing and thermal bonding of poly(methyl methacrylate) microfluidic chip because it supplied constant-temperature heating without electrical control circuits. To emboss a channel plate, a piece of poly(methyl methacrylate) plate was sandwiched between a template and a microscopic glass slide on a positive temperature coefficient ceramic heater. All the assembled components were pressed between two elastic press heads of a spring-driven press while a voltage was applied to the heater for 10 min. Subsequently, the embossed poly(methyl methacrylate) plate bearing negative relief of channel networks was bonded with a piece of poly(methyl methacrylate) cover sheet to obtain a complete microchip using a positive temperature coefficient ceramic heater and a spring-driven press. High quality microfluidic chips fabricated by using the novel embossing/bonding device were successfully applied in the electrophoretic separation of three cations. Positive temperature coefficient ceramic heater indicates great promise for the low-cost production of poly(methyl methacrylate) microchips and should find wide applications in the fabrication of other thermoplastic polymer microfluidic devices.     

一种直接测定微流控芯片电渗流速度的新方法

随着微芯片技术的成熟,越来越迫切地需要有一个准确而简洁的电渗流速度的检测方法。根据荧光物质罗丹明123（Rh123）在不同pH缓冲溶液中迁移时间的变化,推导出Rh123在pH 9和10条件下分别有中性分子存在,而中性分子的移动速度等于电渗流速度,因此建立了直接以Rh123中性分子为标记物测定电渗流速度的方法。通过直接检测Rh123中性分子的迁移时间,计算得出所用玻璃微流控芯片在pH 9.3和pH 10.1的电渗流速度为3.9×10-4 cm2/(s·V)和4.1×10-4 cm2/(s·V),与经典方法对照无明显差异。     

Thermal analysis of nanofluids in microfluidics using an infrared camera

We present the thermal analysis of liquid containing Al(2)O(3) nanoparticles in a microfluidic platform using an infrared camera. The small dimensions of the microchannel along with the low flow rates (less than 120 μl min(-1)) provide very low Reynolds numbers of less than 17.5, reflecting practical parameters for a microfluidic cooling platform. The heat analysis of nanofluids has never been investigated in such a regime, due to the deficiencies of conventional thermal measurement systems. The infrared camera allows non-contact, three dimensional and high resolution capability for temperature profiling. The system was studied at different w/w concentrations of thermally conductive Al(2)O(3) nanoparticles and the experiments were in excellent agreement with the computational fluid dynamics (CFD) simulations.     

Integrated hydrogen leak detector with a tunnel mis structure

A simpler integrated hydrogen leak detector has been fabricated, which consists of a Pd-Si tunnel MIS diode for the hydrogen sensor, a diffused resistor layer for the inside heater and a p-n junction diode for temperature control. Measurements were carried out on the response characteristics to hydrogen at different device temperatures and hydrogen concentrations. The results show that the newly fabricated detector can be used as a practical detector for small leakage of hydrogen at a device temperature between 100 and 120 °C. It is also demonstrated that the tunnel MIS diode with a hole-structure Pd layer drastically improves the hydrogen sensitivity.     

Membrane assisted passive sampler for triazine compounds in water bodies--characterization of environmental conditions and field performance

This article reports the integration of the fiber optic-particle plasmon resonance (FO-PPR) biosensor with a microfluidic chip to reduce response time and improve detection limit. The microfluidic chip made of poly(methyl methacrylate) had a flow-channel of dimensions 4.0 cm × 900 μm × 900 μm. A partially unclad optical fiber with gold or silver nanoparticles on the core surface was placed within the flow-channel, where the volume of the flow space was about 14 μL. Results using sucrose solutions of various refractive indexes show that the refractive index resolution improves by 2.4-fold in the microfluidic system. The microfluidic chip is capable of delivering a precise amount of biological samples to the detection area without sample dilution. Several receptor/analyte pairs were chosen to examine the biosensing capability of the integrated platform: biotin/streptavidin, biotin/anti-biotin, DNP/anti-DNP, OVA/anti-OVA, and anti-MMP-3/MMP-3. Results show that the response time to achieve equilibrium can be shortened from several thousand seconds in a conventional liquid cell to several hundred seconds in a microfluidic flow-cell. In addition, the detection limit also improves by about one order of magnitude. Furthermore, the normalization by using the relative change of transmission response as the sensor output alleviate the demand on precise optical alignment, resulting in reasonably good chip-to-chip measurement reproducibility.     

Parallel single-cell optical transit dielectrophoresis cytometer

In this work, we present an optical transit DEP flow cytometer for parallel single-cell analysis. Each cell's dielectric property is inferred from velocity perturbations due to DEP actuation in a microfluidic channel. Dual LED sources facilitate velocity measurement by producing two transit shadows for each cell passing through the channel. These shadows are detected using a 256-pixel linear optical array detector. Massively parallel analysis is possible as each pixel of the detector can independently analyze the passing cells. A wide channel (∼18 mm) was employed to carry many particles simultaneously, and the system was capable of detecting the velocity of over 200 cells simultaneously. We have achieved analysis rates for 10 µm diameter polystyrene spheres response exceeding 250 per second. With appropriate calibration, this DEP cytometer can quantitatively measure the dielectric response. The dielectric response (Clausius–Mossotti factor) of viable CHO cells was measured over the frequency range of 100 kHz to 6 MHz, and the obtained response matches the previously measured values by our group. The DEP cytometer uses simple modular components to achieve high throughput label-free single-cell dielectric analysis and can begin analyzing particles within 10 s after starting to pump the sample into the channel.     

Electroosmotic flow with Joule heating effects

Electroosmotic flow with Joule heating effects was examined numerically and experimentally in this work. We used a fluorescence-based thermometry technique to measure the liquid temperature variation caused by Joule heating along a micro capillary. We used a caged-fluorescent dye-based microfluidic visualization technique to measure the electroosmotic velocity profile along the capillary. Sharp temperature drops close to the two ends and a high-temperature plateau in the middle of the capillary were observed. Correspondingly, concave-convex-concave velocity profiles were observed in the inlet-middle-outlet regions of a homogeneous capillary. These velocity perturbations were due to the induced pressure gradients resulting from axial variations of temperature. The measured liquid temperature distribution and the electroosmotic velocity profile along the capillary agree well with the predictions of a theoretical model developed in this paper.     

Micro-droplet detection and characterization using thermal responses

We suggest a novel method to detect droplets and determine the protein content of droplets in microfluidic system using the 3ω method, which is a powerful tool to easily detect thermal response changes with a simple device. By measuring the thermal response of droplets and a carrying flow in real time, water droplets in an oleic acid carrying flow can be detected, and the concentration of bovine serum albumin in droplets can be estimated. This method is expected to increase the practicality and power of droplet-based microfluidic systems.