Characterization of microdroplets using optofluidic signals

We develop a simple method to determine the microdroplet features in a microfluidic chip fabricated by conventional soft lithography. Different sizes of microdroplets are generated through a typical microfluidic T-junction by adjusting the flow rates of the two immiscible liquids. Droplet size and content can be determined by monitoring the optofluidic signals reflected at the fluid-polydimethylsiloxane (PDMS) interface. The demonstrated droplet characterization system can be readily integrated with other microfluidic networks, making it promising for biochemical and biosensing applications.     

Fourier microfluidics

We present a new experimental technique for the separation of dynamic chemical signals based on their frequency domain characteristics. Such a technique can be used to create filters that separate slow signals from fast signals from a common input flow stream. The propagation of time-varying chemical waves through networks of microfluidic channels is first examined. Mathematical models and a set of simple experiments are developed that demonstrate that short microfluidic channels behave as linear delay lines. The observed dispersive broadening and delay behavior can be explained in Fourier space in terms of corresponding phase delay, amplitude decay and characteristic transfer functions. Such delay components can be utilized to implement frequency dependent interference filters. An 8th order PDMS bandpass filter chip demonstrating these ideas was constructed. The filter chip has a central frequency of 0.17 Hz and a bandwith of 0.04 Hz at a flow rate of 4 microL h(-1).     

纸基过氯乙烯树脂微流控亚硝酸根离子检测片的研制

基于滤纸上过氯乙烯树脂栏选择性通过亚硝酸根离子, 结合微流控分析装置设计, 研制成纸基过氯乙烯树脂微流控亚硝酸根离子检测芯片. 采用该微流控亚硝酸根离子检测芯片测定了亚硝酸盐样品, 线性范围和检测限分别为70～1500 μmol/L 和48 μmol/L. 该微流控亚硝酸根离子检测芯片已成功应用于水样和食品中亚硝酸盐测定, 结果满意.     

A capillary electrophoresis chip with hydrodynamic sample injection for measurements from a continuous sample flow

A microchip-based capillary electrophoresis device supported by a microfluidic network made of poly(dimethylsiloxane), used for measuring target analytes from a continuous sample flow, is presented. The microsystem was fabricated by means of replica molding in combination with standard microfabrication technologies, resulting in microfluidic components and an electrochemical detector. A new hydrodynamic sample injection procedure is introduced, and the maximum number of consecutive measurements that can be made with a poly(dimethylsiloxane) capillary electrophoresis chip with amperometric detection is investigated with respect to reproducibility. The device features a high degree of functional integration, so the benefits associated with miniaturized analysis systems apply to it.     

Size-controlled fabrication of supramolecular vesicles for the construction of conjugated polymer sensors with enhanced optical properties

Polymerizable supramolecular monomer vesicles are readily fabricated by employing a hydrodynamic focusing method on a microfluidic chip. The polymerized diacetylenene nanovesicles, generated using the microfluidic method, display an improved fluorescence property compared to those prepared by employing a conventional bulk method. The flexibility of the vesicle size control by manipulating the flow conditions is another significant feature of the new microfluidic approach.     

Inverse‐Opal Conducting Polymer Monoliths in Microfluidic Channels

Inverse opal monolithic flow‐through structures of conducting polymer (CP) were achieved in microfluidic channels for lab‐on‐a‐chip (LOC) applications. In order to achieve the uniformly porous monolith, polystyrene (PS) colloidal crystal (CC) templates were fabricated in microfluidic channels. Consequently, an inverse opal polyaniline (PANI) structure was achieved on‐chip, through a two‐step process involving the electrochemical growth of PANI and subsequent removal of the template. In this work the effect of CP electropolymerisation time on these structures is discussed. It was found that growth time is critical in achieving an ordered structure with well‐defined flow‐through pores. This is significant as these optimised porous structures will allow for maximising the surface area of the monolith and will also result in well‐defined flow profiles through the microchannel.     

A smart and portable micropump for stable liquid delivery

Precise and reliable liquid delivery is vital for microfluidic applications. Here, we illustrate the design, fabrication, characterization, and application of a portable, low cost, and robust micropump, which brings solution to stable liquid delivery in microfluidic environment. The pump is designed with three optional speeds of different pumping flow rates, and it can be simply actuated by spring‐driven mechanism. The different flow rates of the pump are realized via passive microvalves in a compact microfluidic chip, which is installed in the pump. Importantly, the membrane structures of the microvalves allow accurate liquid control, and stable flow rates can be achieved via a spring setup. The proposed pump is applied to continuously and stably infuse microbead suspension into an inertial microfluidic chip, and good particle focusing is realized in the spiral channel of the inertial microfluidic chip. The proposed portable, self‐powered, and cost‐efficient pump is crucial for microfluidic lab‐on‐a‐chip system integration, which may facilitate microfluidic application for precise liquid delivery, control, measurement, and analysis.     

Squeeze-chip: a finger-controlled microfluidic flow network device and its application to biochemical assays

We designed and fabricated a novel microfluidic device that can be operated through simple finger squeezing. On-chip microfluidic flow control is enabled through an optimized network of check-valves and squeeze-pumps. The sophisticated flow system can be easily constructed by combining a few key elements. We implemented this device to perform quantitative biochemical assays with no requirement for precision instruments.     

Rapid fabrication of electrochemical enzyme sensor chip using polydimethylsiloxane microfluidic channel

Applicability of polydimethylsiloxane (PDMS) for easy and rapid fabrication of enzyme sensor chips, based on electrochemical detection, is examined. The sensor chip consists of PDMS substrate with a microfluidic channel fabricated in it, and a glass substrate with enzyme-modified microelectrodes. The two substrates are clamped together between plastic plates. The sensor chip has shown no leakage around the microelectrodes under continuous solution flow (34 μl/min). Amperometric response of the sensor chips developed in this work suggest that various types of enzyme sensors can be designed by using PDMS microfluidic channels.     

Fuel cell-powered microfluidic platform for lab-on-a-chip applications

The achievement of a higher degree of integration of components--especially micropumps and power sources--is a challenge currently being pursued to obtain portable and totally autonomous microfluidic devices. This paper presents the integration of a micro direct methanol fuel cell (μDMFC) in a microfluidic platform as a smart solution to provide both electrical and pumping power to a Lab-on-a-Chip system. In this system the electric power produced by the fuel cell is available to enable most of the functionalites required by the microfluidic chip, while the generated CO(2) from the electrochemical reaction produces a pressure capable of pumping a liquid volume through a microchannel. The control of the fuel cell operating conditions allows regulation of the flow rate of a liquid sample through a microfluidic network. The relation between sample flow rate and the current generated by the fuel cell is practically linear, achieving values in the range of 4-18 μL min(-1) while having an available power between 1-4 mW. This permits adjusting the desired flow rate for a given application by controlling the fuel cell output conditions and foresees a fully autonomous analytical Lab-on-a-Chip in which the same device would provide the electrical power to a detection module and at the same time use the CO(2) pumping action to flow the required analytes through a particular microfluidic design.     

Surface-enhanced Raman scattering (SERS) optrodes for multiplexed on-chip sensing of nile blue A and oxazine 720

The fabrication and on-chip integration of surface-enhanced Raman scattering (SERS) optrodes are presented. In the optrode configuration, both the laser excitation and the back-scattered Raman signal are transmitted through the same optical fiber. The SERS-active component of the optrode was fabricated through the self-assembly of silver nanoparticles on the tip of optical fibers. The application of SERS optrodes to detect dyes in aqueous solution indicated a limit of quantification below 1 nM, using nile blue A as a molecular probe. Using the optrode-integrated microfluidic chip, it was possible to detect several different dyes from solutions sequentially injected into the same channel. This approach for sequential detection of different analytes is applicable to monitoring on-chip chemical processes. The narrow bandwidth of the vibrational information generated by SERS allowed solutions of different compositions of two chemically similar dyes to be distinguished using a dilution microfluidic chip. These results demonstrate the advantages of the SERS-optrode for microfluidics applications by illustrating the potential of this vibrational method to quantify components in a mixture.     

Waveguide confined Raman spectroscopy for microfluidic interrogation

We report the first implementation of the fiber based microfluidic Raman spectroscopic detection scheme, which can be scaled down to micrometre dimensions, allowing it to be combined with other microfluidic functional devices. This novel Raman spectroscopic detection scheme, which we termed as Waveguide Confined Raman Spectroscopy (WCRS), is achieved through embedding fibers on-chip in a geometry that confines the Raman excitation and collection region which ensures maximum Raman signal collection. This results in a microfluidic chip with completely alignment-free Raman spectroscopic detection scheme, which does not give any background from the substrate of the chip. These features allow a WCRS based microfluidic chip to be fabricated in polydimethylsiloxane (PDMS) which is a relatively cheap material but has inherent Raman signatures in fingerprint region. The effects of length, collection angle, and fiber core size on the collection efficiency and fluorescence background of WCRS were investigated. The ability of the device to predict the concentration was studied using urea as a model analyte. A major advantage of WCRS is its scalability that allows it to be combined with many existing microfluidic functional devices. The applicability of WCRS is demonstrated through two microfluidic applications: reaction monitoring in a microreactor and detection of analyte in a microdroplet based microfluidic system. The WCRS approach may lead to wider use of Raman spectroscopy based detection in microfluidics, and the development of portable, alignment-free microfluidic devices.     

A serial dilution microfluidic device using a ladder network generating logarithmic or linear concentrations

In this paper, we propose a serial dilution microfluidic chip which is able to generate logarithmic or linear step-wise concentrations. These concentrations were generated via adjustments in the flow rate of two converging fluids at the channel junctions of the ladder network. The desired dilution ratios are almost independent of the flow rate or diffusion length of molecules, as the dilution device is influenced only by the ratio of volumetric flow rates. Given a set of necessary dilution ratios, whether linear or logarithmic, a serial dilution chip can be constructed via the modification of a microfluidic resistance network. The design principle was suggested and both the logarithmic and linear dilution chips were fabricated in order to verify their performance in accordance with the fluorescence intensity. The diluted concentrations of a fluorescein solution in the microfluidic device evidenced relatively high linearity, and the cytotoxicity test of MCF-7 breast cancer cells via the logarithmic dilution chip was generally consistent with the results generated with manual dilution.     

Integrated circuit/microfluidic chip to programmably trap and move cells and droplets with dielectrophoresis

We present an integrated circuit/microfluidic chip that traps and moves individual living biological cells and chemical droplets along programmable paths using dielectrophoresis (DEP). Our chip combines the biocompatibility of microfluidics with the programmability and complexity of integrated circuits (ICs). The chip is capable of simultaneously and independently controlling the location of thousands of dielectric objects, such as cells and chemical droplets. The chip consists of an array of 128 x 256 pixels, 11 x 11 microm(2) in size, controlled by built-in SRAM memory; each pixel can be energized by a radio frequency (RF) voltage of up to 5 V(pp). The IC was built in a commercial foundry and the microfluidic chamber was fabricated on its top surface at Harvard. Using this hybrid chip, we have moved yeast and mammalian cells through a microfluidic chamber at speeds up to 30 microm sec(-1). Thousands of cells can be individually trapped and simultaneously positioned in controlled patterns. The chip can trap and move pL droplets of water in oil, split one droplet into two, and mix two droplets into one. Our IC/microfluidic chip provides a versatile platform to trap and move large numbers of cells and fluid droplets individually for lab-on-a-chip applications.     

Integrated microfabricated systems including a purification module and an on-chip nano electrospray ionization interface for biological analysis

We report here on an integrated microfabricated device dedicated to the preparation of biological samples prior to their on-line analysis by electrospray ionization-mass spectrometry (ESI-MS). This microfluidic device is fabricated using the negative photoresist SU-8 by microtechnology techniques. The device includes a chromatographic module plus an ESI interface for MS. The chromatographic module is dedicated to sample purification and is based on a polymer monolithic phase which includes hydrophobic moieties. The ESI interface is integrated onto the chip and is based on a capillary slot. We present here the integration of these different modules onto a single system that is fabricated via a SU-8-based microtechnology route. We present also their testing for the purification of peptide samples. This started with a partial integration step with the combination of at least two of the modules (microsystem + monolith; microsystem + nib) and their test before the fabrication and testing of fully integrated microsystems.     

On-chip electrochemical detection of CdS quantum dots using normal and multiple recycling flow through modes

A flexible hybrid polydimethylsiloxane (PDMS)-polycarbonate (PC) microfluidic chip with integrated screen printed electrodes (SPE) was fabricated and applied for electrochemical quantum dots (QDs) detection. The developed device combines the advantages of flexible microfluidic chips, such as their low cost, the possibility to be disposable and amenable to mass production, with the advantages of electrochemistry for its facility of integration and the possibility to miniaturize the analytical device. Due to the interest in biosensing applications in general and particularly the great demand for labelling alternatives in affinity biosensors, the electrochemistry of cadmium sulfide quantum dots (CdS QDs) is evaluated. Square wave anodic stripping voltammetry (SWASV) is the technique used due to its sensitivity and low detection limits that can be achieved. The electrochemical as well as the microfluidic parameters of the developed system are optimized. The detection of CdS QDs in the range between 50 to 8000 ng mL(-1) with a sensitivity of 0.0009 μA/(ng mL(-1)) has been achieved. In addition to the single in-chip flow through measurements, the design of a recirculation system with the aim of achieving lower detection limits using reduced volumes (25 μL) of sample was proposed as a proof-of-concept.     

Microfluidic very large scale integration (mVLSI) with integrated micromechanical valves

Microfluidic chips with a high density of control elements are required to improve device performance parameters, such as throughput, sensitivity and dynamic range. In order to realize robust and accessible high-density microfluidic chips, we have fabricated a monolithic PDMS valve architecture with three layers, replacing the commonly used two-layer design. The design is realized through multi-layer soft lithography techniques, making it low cost and easy to fabricate. By carefully determining the process conditions of PDMS, we have demonstrated that 8 × 8 and 6 × 6 μm(2) valve sizes can be operated at around 180 and 280 kPa differential pressure, respectively. We have shown that these valves can be fabricated at densities approaching 1 million valves per cm(2), substantially exceeding the current state of the art of microfluidic large-scale integration (mLSI) (thousands of valves per cm(2)). Because the density increase is greater than two orders of magnitude, we describe this technology as microfluidic very large scale integration (mVLSI), analogous to its electronic counterpart. We have captured and tracked fluorescent beads, and changed the electrical resistance of a fluidic channel by using these miniaturized valves in two different experiments, demonstrating that the valves are leakproof. We have also demonstrated that these valves can be addressed through multiplexing.     

Integrating advanced functionality in a microfabricated high-throughput fluorescent-activated cell sorter

The integration of complete analyses systems "on chip" is one of the great potentials of microfabricated devices. In this study we present a new pressure-driven microfabricated fluorescent-activated cell sorter chip with advanced functional integration. Using this sorter, fluorescent latex beads are sorted from chicken red blood cells, achieving substantial enrichments at a sample throughput of 12000 cells s(-1). As a part of the sorter chip, we have developed a monolithically integrated single step coaxial flow compound for hydrodynamic focusing of samples in flow cytometry and cell sorting. The structure is simple, and can easily be microfabricated and integrated with other microfluidic components. We have designed an integrated chamber on the chip for holding and culturing of the sorted cells. By integrating this chamber, the risk of losing cells during cell handling processes is eliminated. Furthermore, we have also developed integrated optics for cell detection. Our new design contributes to the ongoing efforts for building a fully integrated micro cell sorting and analysing system.     

CO2 laser microfabrication of an integrated polymer microfluidic manifold for the determination of phosphorus

A simple colorimetric technique is implemented in a polymer microfluidic manifold. The simple chemistry aids an uncomplicated microchannel design, which is fabricated by CO(2) laser ablation. Issues such as bonding of multiple layers, alignment of micro-fabricated structures and integration of optical components are addressed. A demonstration of a stopped flow regime in the microfluidic manifold is also presented.     

AAO-CNTs electrode on microfluidic flow injection system for rapid iodide sensing

In this work, carbon nanotubes (CNTs) nanoarrays in anodized aluminum oxide (AAO-CNTs) nanopore is integrated on a microfluidic flow injection system for in-channel electrochemical detection of iodide. The device was fabricated from PDMS (polydimethylsiloxane) microchannel bonded on glass substrates that contains three-electrode electrochemical system, including AAO-CNTs as a working electrode, silver as a reference electrode and platinum as an auxiliary electrode. Aluminum, stainless steel catalyst, silver and platinum layers were sputtered on the glass substrate through shadow masks. Aluminum layer was then anodized by two-step anodization process to form nanopore template. CNTs were then grown in AAO template by thermal chemical vapor deposition. The amperometric detection of iodide was performed in 500-μm-wide and 100-μm-deep microchannels on the microfluidic chip. The influences of flow rate, injection volume and detection potential on the current response were optimized. From experimental results, AAO-CNTs electrode on chip offers higher sensitivity and wider dynamic range than CNTs electrode with no AAO template.