On-chip Mixer Research Articles

Preparing Fluid Samples Under Retention Time Constraints Using Flow-Based Microfluidic Biochips

Sample preparation is an essential step in almost all bioprotocols, which can be efficiently achieved via sequence of mixing steps called mixing graph. In literature, several techniques have been reported to determine a mixing graph with the minimal number of mixing steps, or the minimal usage of reagent fluids, or the minimal wastage, or sometime a combination of them. The retention time of an flow-based microfluidic biochip (FMB) is defined as the maximum duration for which a fluid can be stored within a microchannel without any fluid leakage. However, the retention time has not yet been considered as a scheduling constraint during automation of the sample preparation using an FMB in order to obtain the scheduled mixing graphs. In this paper, we propose a retention time aware scheduling method called time aware list scheduling ( TALS), which can be used with the state-of-the-art methods, and a new satisfiability based mixing algorithm called time aware sample preparation ( TASP) to obtain the scheduled mixing graph for a target ratio satisfying the retention time constraint and the number of available on-chip mixers in an FMB. Simulation results suggest that on an average TALS always outperforms a baseline scheduling method, while scheduling any mixing graph. Whereas, TASP can determine the optimal and scheduled mixing graphs compared to the existing mixing methods combined with TALS.

Push/Pull Inequality Based High-Speed On-Chip Mixer Enhanced by Wettability.

In this paper, a high-speed on-chip mixer using two effects is proposed, i.e., push/pull inequality and wettability. Push/pull inequality and wettability are effective for generating a rotational fluid motion in the chamber and for enhancing the rotational speed by reducing the viscous loss between the liquid and channel wall, respectively. An on-chip mixer is composed of three components, a microfluidic channel for making the main fluid flow, a circular chamber connected to the channel for generating a rotational flow, and an actuator connected at the end of the channel allowing a push/pull motion to be applied to the liquid in the main channel. The flow patterns in the chamber under push/pull motions are nonreversible for each motion and, as a result, produce one-directional torque to the fluid in the circular chamber. This nonreversible motion is called push/pull inequality and eventually creates a swirling flow in the chamber. Using hydrophilic treatments, we executed the experiment with a straight channel and a circular chamber to clarify the mixing characteristics at different flow speeds. According to the results, it is confirmed that the swirling velocity under appropriately tuned wettability is 100 times faster than that without tuning.

High-Speed On-Chip Mixing by Microvortex Generated by Controlling Local Jet Flow Using Dual Membrane Pumps

Robot integrated microfluidic chip is a key technology for microscale applications. Recently, the technology has been applied to on-chip mixing, which mix solutions on a microfluidic chip because it is a promising tool to analyze not only the chemical reaction with the small sample volume, but also the response of cells to environmental changes. However, these conventional mixing methods require the mixing time of millisecond-order due to the difficulty of mixing in the laminar condition of a microchannel whose Reynolds number tends to be low. In this letter, we propose a high-speed on-chip mixing by the microvortex generated by controlling local jet flow using dual-membrane pumps. First, we confirmed that vortex was successfully generated within 20 $\mu$ s by the local jet flow. The velocity and Reynolds number were analytically estimated as approximately 20 m/s and ${\text{1.6}} \times \text{10}^{\text{3}}$ , respectively. Second, we evaluated the response time of the mixing using the microvortex. We mixed 200-nm nanobead suspension and the DI water in the velocity of main flow of 1 m/s. By measuring the intensity at the certain observation area, we confirmed that our method successfully mixed solutions and the mixing time was approximately 500 $\mu$ s, whose speed has not been achieved by conventional robot integrated on-chip mixers. Moreover, we confirmed that our system can control the concentration of mixed flow by controlling flow rate ratio of sample and sheath flow. From these results, we confirmed that we achieved high-speed on-demand on-chip mixing by the microvortex.

Design, modelling and simulation of a monolithic high-Tc superconducting terahertz mixer

This paper presents a novel concept and design of a full monolithic integrated high-Tc superconducting (HTS) Josephson junction terahertz (THz) harmonic mixer coupled with a circularly polarized (CP) antenna. The fully on-chip mixer device is very compact in size and utilizes the CP antenna to enhance the polarization orientation flexibility in coupling THz radiation. Electromagnetic simulations are carried out to optimize the coupling efficiency and axial ratio of the THz CP antenna, and the signal transmission and isolation characteristics of the monolithic circuit. An equivalent circuit model of the HTS THz mixer is then established and simulation is performed based on our previously measured step-edge Josephson junction characteristics to evaluate the device performance and validate the concept of design. The results show that a superior performance could be achieved from such a monolithic HTS mixer device, which is significantly better than any HTS THz harmonic mixers reported to date.

Frequency-Hopped Quadrature Frequency Synthesizer in 0.13-$\mu$m Technology

This paper presents a Wireless-USB/WiMedia-compliant fast-hopping frequency synthesizer architecture with quadrature outputs based on sub-harmonic injection-locking. The synthesizer features a cross-coupled quadrature digitally-controlled oscillator, that is injection-locked to a sub-harmonic frequency. An intuitive closed-form expression for the dynamics of the quadrature injection-locked oscillator and a technique to achieve fast frequency-hopping, are presented. The overall architecture, based on this technique, is a CMOS-only implementation and has been fabricated in a 0.13-μm SiGe BiCMOS process. On-chip mixers have been implemented to measure the quadrature accuracy of the outputs. Measurement results indicate lock-times of less than 2.5 ns, a locked phase noise of -114 dBc/Hz at 1 MHz offset and a quadrature accuracy of better than 0.5°. The frequency synthesizer (excluding output buffers) occupies an area of 0.27 mm2 and consumes 14.5 mW of power. The best and worst case spur suppression achieved are 47 and 31 dB, respectively. This is the lowest power fast-hopping quadrature frequency synthesizer that has been reported to date.

60 GHz wide tuning range SiGe bipolar voltage controlled oscillator for high definition multimedia interface and wireless docking applications

A wide tuning range voltage controlled oscillator (VCO) with novel architecture is proposed in this work. The entire circuit consists of a VCO core, a summing circuit, a single-ended to differential (STD) converter and a buffer amplifier. The VCO core oscillates at half the desired frequency and the second harmonic of the VCO core is extracted by the summing circuit, which is then converted to a differential pair by the STD. The entire VCO circuit operates from 58.85 to 70.85 GHz with 20% frequency tuning range. The measured VCO gain is less than 1.6 GHz/V. The measured phase noise at 3 MHz offset is less than -78 dBc/Hz across the entire tuning range. The differential phase error of the output signals is measured by down converting the VCO output signals to low gigahertz frequency using an on-chip mixer. The measured differential phase error is less than 8°. The VCO circuit, which is constructed using 0.35 μm SiGe technology, occupies 770 × 550 μm 2 die area and consumes 62 mA under 3.5 V supply.

An integrated disposable device for DNA extraction and helicase dependent amplification.

Here we report the demonstration of an integrated microfluidic chip that performs helicase dependent amplification (HDA) on samples containing live bacteria. Combined chip-based sample preparation and isothermal amplification are attractive for world health applications, since the need for instrumentation to control flow rate and temperature changes are reduced or eliminated. Bacteria lysis, nucleic acid extraction, and DNA amplification with a fluorescent reporter are incorporated into a disposable polymer cartridge format. Smart passive fluidic control using a flap valve and a hydrophobic vent (with a nanoporous PTFE membrane) with a simple on-chip mixer eliminates multiple user operations. The device is able to detect as few as ten colony forming units (CFU) of E. coli in growth medium.

Concentration and Purification of Human Immunodeficiency Virus Type 1 Virions by Microfluidic Separation of Superparamagnetic Nanoparticles

The low concentration and complex sample matrix of many clinical and environmental viral samples presents a significant challenge in the development of low cost, point-of-care viral assays. To address this problem, we investigated the use of a microfluidic passive magnetic separator combined with on-chip mixer to both purify and concentrate whole-particle human immunodeficiency virus type 1 (HIV-1) virions. Virus-containing plasma samples are first mixed to allow specific binding of the viral particles with antibody-conjugated superparamagnetic nanoparticles, and several passive mixer geometries were assessed for their mixing efficiencies. The virus-nanoparticle complexes are then separated from the plasma in a novel magnetic separation chamber, where packed micrometer-sized ferromagnetic particles serve as high magnetic gradient concentrators for an externally applied magnetic field. Thereafter, a viral lysis buffer was flowed through the chip and the released HIV proteins were assayed off-chip. Viral protein extraction efficiencies of 62% and 45% were achieved at 10 and 30 muL/min throughputs, respectively. More importantly, an 80-fold concentration was observed for an initial sample volume of 1 mL and a 44-fold concentration for an initial sample volume of 0.5 mL. The system is broadly applicable to microscale sample preparation of any viral sample and can be used for nucleic acid extraction as well as 40-80-fold enrichment of target viruses.

Design and measurement of a 53 GHz balanced Colpitts oscillator

A 53 GHz Colpitts oscillator implemented in a SiGe:C BiCMOS technology is presented. Limited by a 26.5 GHz frequency analyzer, the oscillator was measured indirectly through an on-chip mixer. The mixer down-converted the oscillating frequency to an intermediate frequency (IF) below 26.5 GHz. By adjusting the local oscillating (LO) frequency and recording the changes of IF frequency, the oscillator's output frequency (RF) was determined. Additionally, using phase noise theory of mixers, the oscillator's phase noise was estimated as –58 dBc/Hz at 1 MHz offset and the output power was about –21 dBm. The chip is 270 × 480 μm in size.

Design of Interactively Time-Pulsed Microfluidic Mixers in Microchips using Numerical Simulation

In this paper, we propose a novel technique in which driving voltages are applied interactively to the respective inlet fluid flows of three configurations of a microfluidic device, namely T-shaped, double-T-shaped, and double-cross-shaped configurations, to induce electroosmotic flow (EOF) velocity variations in such a way as to develop a rapid mixing effect in the microchannel. In these configurations a microfluidic mixer apply only one electrokinetic driving force, which drives the sample fluids and simultaneously produces a periodic switching frequency. It requires no other external driving force to induce perturbations to the flow field. The effects of the main applied electric field, the interactive frequency, and the pullback electric field on the mixing performance are thoroughly examined numerically. The optimal interactive frequency range for a given set of micromixer parameters is identified for each type of control mode. The numerical results confirm that micromixers operating at an optimal interactive frequency are capable of delivering a significantly enhanced mixing performance. Furthermore, it is shown that the optimal interactive frequency depends upon the magnitude of the main applied electric field. The interactively pulsed mixers developed in this study have a strong potential for use in lab-on-a-chip systems. They involve a simpler fabrication process than either passive or active on-chip mixers and require less human intervention in operation than their bulky external counterparts.

A 2.5-GHz eight-phase VCO in SiGe BiCMOS technology

We present a 2.5-GHz voltage-controlled oscillator (VCO) with eight equally distributed phases derived from a 10-GHz LC VCO. Stochastic and static phase errors were obtained by spectrum analyzer measurements in conjunction with an on-chip single-sideband mixer. From the measured phase noise spectrum, we predict an absolute rms jitter contribution of 130 fs in a 2-MHz bandwidth phase-locked loop. A static phase error of less than 0.7/spl deg/ was deduced from the sideband suppression. The eight-phase VCO is tunable from 2.35 to 2.85 GHz and draws 16 mA from a 2.0-V supply. Possible applications include clock and data recovery of a 10-Gb/s signal in a fiber-optic receiver as well as high-precision image rejection receivers and I/Q direct up-converters for radio-frequency applications.

Microchip systems for immunoassay: an integrated immunoreactor with electrophoretic separation for serum theophylline determination

A glass microchip is described in which reagents and serum samples for competitive immunoassay of serum theophylline can be mixed, reacted, separated, and analyzed. The device functions as an automated microfluidic immunoassay system, creating a lab-on-a-chip. Electroosmotic pumping was used to control first the mixing of 50-fold-diluted serum sample with labeled theophylline tracer in a 1:1 ratio, followed by 1:1 mixing and reaction with anti-theophylline antibody. The 51-nL on-chip mixer gave the same concentration as dilution performed off-chip, within 3%. A 100-pL plug of the reacted solution was then injected into an electrophoresis separation channel integrated within the same chip. Measurements of free and bound tracer by fluorescence detection gave linear calibration curves of signal vs log[theophylline] between 0 and 40 mg/L, with a slope of 0.52 +/- 0.03 and an intercept of -0.04 +/- 0.04 after a 90-s reaction time. A detection limit of 0.26 mg/L in serum (expressed before the dilution step, actual concentration of 1.3 micrograms/L at the detector) was obtained. Recovery values were 107% +/- 8% for 15 mg/L serum samples.