Silicon Microfluidic Channels Research Articles

Enhancement of faradaic current in an electrochemical cell integrated into silicon microfluidic channels

Implantable electrochemical sensors enable fast and sensitive detection of analytes in biological tissue, but are hampered by bio-foulant attack and are unable to be recalibrated in-situ. Herein, an electrochemical sensor integrated into ultra-low flow (nL/min) silicon microfluidic channels for protection from foulants and in-situ calibration is demonstrated. The small footprint (5 µm radius channel cross-section) of the device allows its integration into implantable sampling probes for monitoring chemical concentrations in biological tissues. The device is designed for fast scan cyclic voltammetry (FSCV) in the thin-layer regime when analyte depletion at the electrode is efficiently compensated by microfluidic flow. A 3X enhancement of faradaic peak currents is observed due to the increased flux of analytes towards the electrodes. Numerical analysis of in-channel analyte concentration confirmed near complete electrolysis in the thin-layer regime below 10 nL/min. The manufacturing approach is highly scalable and reproducible as it utilizes standard silicon microfabrication technologies.

Carbon Nanotubes Film Integrated With Silicon Microfluidic Channel for a Novel Composite THz Metasurface

Owing to the unique electromagnetic response ability, artificial electromagnetic metasurfaces have potential applications in medical, imaging, sensing, and other fields. In this paper, a novel composite THz metasurface integrated by carbon nanotubes (CNTs) resonant metasurface and silicon microfluidic channel has been proposed, which combines the advantages of semiconductor and carbon nanotubes film materials. The absorption characteristics and the refractive index sensing capabilities are investigated comprehensively. Calculation results show that two obvious resonant absorption peaks located at 1.20 THz and 1.85 THz and the absorption is nearly 99.6% and 89.8%, respectively; the device performs a good linear relationship between the position of resonant absorption peaks and the refractive index, and the frequency sensitivity can achieve 492 GHz/RIU. The influence of structural parameters and the offset of the center of the CNTs metasurface on the absorption spectrum demonstrate that the novel composite metasurface has a good reliability and stability and can be used for sensing various materials in other frequency regions range from radio frequency through THz and to the infrared regime. This novel composite metasurface has good biocompatibility and low cost, which widens the application range of terahertz functional devices.

Characterization and Separation of Live and Dead Yeast Cells Using CMOS-Based DEP Microfluidics

This study aims at developing a miniaturized CMOS integrated silicon-based microfluidic system, compatible with a standard CMOS process, to enable the characterization, and separation of live and dead yeast cells (as model bio-particle organisms) in a cell mixture using the DEP technique. DEP offers excellent benefits in terms of cost, operational power, and especially easy electrode integration with the CMOS architecture, and requiring label-free sample preparation. This can increase the likeliness of using DEP in practical settings. In this work the DEP force was generated using an interdigitated electrode arrays (IDEs) placed on the bottom of a CMOS-based silicon microfluidic channel. This system was primarily used for the immobilization of yeast cells using DEP. This study validated the system for cell separation applications based on the distinct responses of live and dead cells and their surrounding media. The findings confirmed the device’s capability for efficient, rapid and selective cell separation. The viability of this CMOS embedded microfluidic for dielectrophoretic cell manipulation applications and compatibility of the dielectrophoretic structure with CMOS production line and electronics, enabling its future commercially mass production.

Towards CMOS Integrated Microfluidics Using Dielectrophoretic Immobilization.

Dielectrophoresis (DEP) is a nondestructive and noninvasive method which is favorable for point-of-care medical diagnostic tests. This technique exhibits prominent relevance in a wide range of medical applications wherein the miniaturized platform for manipulation (immobilization, separation or rotation), and detection of biological particles (cells or molecules) can be conducted. DEP can be performed using advanced planar technologies, such as complementary metal-oxide-semiconductor (CMOS) through interdigitated capacitive biosensors. The dielectrophoretically immobilization of micron and submicron size particles using interdigitated electrode (IDE) arrays is studied by finite element simulations. The CMOS compatible IDEs have been placed into the silicon microfluidic channel. A rigorous study of the DEP force actuation, the IDE’s geometrical structure, and the fluid dynamics are crucial for enabling the complete platform for CMOS integrated microfluidics and detection of micron and submicron-sized particle ranges. The design of the IDEs is performed by robust finite element analyses to avoid time-consuming and costly fabrication processes. To analyze the preliminary microfluidic test vehicle, simulations were first performed with non-biological particles. To produce DEP force, an AC field in the range of 1 to 5 V (peak-to-peak) is applied to the IDE. The impact of the effective external and internal properties, such as actuating DEP frequency and voltage, fluid flow velocity, and IDE’s geometrical parameters are investigated. The IDE based system will be used to immobilize and sense particles simultaneously while flowing through the microfluidic channel. The sensed particles will be detected using the capacitive sensing feature of the biosensor. The sensing and detecting of the particles are not in the scope of this paper and will be described in details elsewhere. However, to provide a complete overview of this system, the working principles of the sensor, the readout detection circuit, and the integration process of the silicon microfluidic channel are briefly discussed.

Non-Lithographic Silicon Micromachining Using Inkjet and Chemical Etching.

We introduce a non-lithographical and vacuum-free method to pattern silicon. The method combines inkjet printing and metal assisted chemical etching (MaCE); we call this method “INKMAC”. A commercial silver ink is printed on top of a silicon surface to create the catalytic patterns for MaCE. The MaCE process leaves behind a set of silicon nanowires in the shape of the inkjet printed micrometer scale pattern. We further show how a potassium hydroxide (KOH) wet etching process can be used to rapidly etch away the nanowires, producing fully opened cavities and channels in the shape of the original printed pattern. We show how the printed lines (width 50–100 µm) can be etched into functional silicon microfluidic channels with different depths (10–40 µm) with aspect ratios close to one. We also used individual droplets (minimum diameter 30 µm) to produce cavities with a depth of 60 µm and an aspect ratio of two. Further, we discuss using the structured silicon substrate as a template for polymer replication to produce superhydrophobic surfaces.

Effect of Laser-Induced Heating on Raman Measurement within a Silicon Microfluidic Channel

When Raman microscopy is adopted to detect the chemical and biological processes in the silicon microfluidic channel, the laser-induced heating effect will cause a temperature rise in the sample liquid. This undesired temperature rise will mislead the Raman measurement during the temperature-influencing processes. In this paper, computational fluid dynamics simulations were conducted to evaluate the maximum local temperature-rise (MLT). Through the orthogonal analysis, the sensitivity of potential influencing parameters to the MLT was determined. In addition, it was found from transient simulations that it is reasonable to assume the actual measurement to be steady-state. Simulation results were qualitatively validated by experimental data from the Raman measurement of diffusion, a temperature-dependent process. A correlation was proposed for the first time to estimate the MLT. Simple in form and convenient for calculation, this correlation can be efficiently applied to Raman measurement in a silicon microfluidic channel.

Plastic light coupler for absorbance detection in silicon microfluidic channels

We present a micro-optical system for ultraviolet/visible absorbance detection in silicon microfluidic channels, which consists of a micro-optical light coupler placed on top of the silicon fluidic channel to probe the molecules under test with laser light. We use nonsequential optical ray-tracing simulations to model the system and to optimize its performance with respect to optical efficiency and system complexity. Deep Proton Writing is used to prototype the plastic light coupler and its spacer baseplate which contains marks to align the micro-optics with respect to the microfluidic channel and which allows for an accurate control of the position of the micro-optics with respect to the excitation source. We demonstrate the proof of concept of this microfluidic light probe by measuring standard samples of coumarin 102 dye with concentrations between 0.6 µM and 6 mM. Calibrating the system yields a detection limit of 4.3 µM. To conclude, we show that the concept of this microfluidic detection system is generic in that it can be applied at different positions on different microfluidic channel configurations.

Scintillation detectors based on silicon microfluidic channels

Microfluidic channels obtained by SU-8 photolithography and filled with liquid scintillators were recently demonstrated to be an interesting technology for the implementation of novel particle detectors.The main advantages of this approach are the intrinsic radiationresistance resulting from the simple microfluidic circulation of theactive medium and the possibility to manufacture devices with highspatial resolution and low material budget using microfabricationtechniques.Here we explore a different technological implementation of thisconcept, reporting on scintillating detectors based on siliconmicrofluidic channels. A process for manufacturing microfluidicdevices on silicon substrates, featuring microchannel arrays suitablefor light guiding, was developed. Such process can be in principlecombined with standard CMOS processing and lead to a tight integrationwith the readout photodetectors and electronics in the future.Several devices were manufactured, featuring microchannel geometriesdiffering in depth, width and pitch. A preliminary characterizationof the prototypes was performed by means of a photomultiplier tubecoupled to the microchannel ends, in order to detect the scintillationlight produced upon irradiation with beta particles from a90Sr source. The photoelectron spectra thusobtained were fitted with the expected output function in order toextract the light yield.

Single-step fabrication of microfluidic channels filled with nanofibrous membrane using femtosecond laser irradiation

In this paper, we demonstrate a new method of fabricating silicon microfluidic channels filled with a porous nanofibrous structure utilizing a femtosecond laser. The nanofibrous structure can act as a membrane used for microfiltration. This method allows us to generate both the microfluidic channel and the fibrous nanostructure in a single step under ambient conditions. Due to laser irradiation, a large number of nanoparticles ablate from the channel surface, and then aggregate and grow into porous nanofibrous structures and fill the channels. Energy dispersive x-ray spectroscopy (EDS) analysis was conducted to examine the oxygen concentration in the membrane structure. Our results demonstrated that by controlling the laser parameters including pulse repetition, pulse width and scanning speed, different microfluidic channels with a variety of porosity could be obtained.

Bioaffinity limitations for anisotropically etched silicon microfluidics

Immobilisation of biological specimens is an essential process in biomicrofluidics for micro total analysis systems (μTASs) applications, to carry out high throughput bioassays. Closed microfluidic channels restrict immobilisation feasibilities to only direct conjugation of the biomolecules with the channel surface through appropriate flow control-based incubation techniques. In this work, the limitations of bioaffinity on anisotropically etched silicon microfluidic channels have been studied. The flow behaviour within the microchannels has been analysed by solving the Navier-Stokes equation using finite element method (FEM). The results have been used to predict the immobilisation and rinsing behaviour within anisotropically etched trapezoidal and triangular microfluidic channels.

Design, fabrication and characterization of nano‐filters in silicon microfluidic channels based on MEMS technology

Since most clinical assays are performed on cell-free serum or plasma, micro-analytical systems for blood tests require integrated on-chip microfluidics for the isolation of plasma or serum from crude blood samples. In this paper, we present a crossflow filtration method using novel silicon nano-filters for plasma separation. The microfluidic chip is made of a silicon substrate containing micropillar arrays, feed channels, side channels and nano-gap structures, sealed with a PDMS-glass compound cover. The design of the silicon filtration structures were optimized using numerical analysis and the optimal MEMS fabrication procedures were obtained. The filtration structures including nano-filters were characterized using SEM and subsequently used to isolate plasma from whole blood in a continuous manner. Compared with micro-gap structures in silicon microfluidic channels, the nano-gap structures have been used to separate plasma from whole blood samples with higher selectivity, where a maximum plasma selectivity of 97.7% has been obtained. Common problems of clogging and jamming in filtration applications have seldom been noticed in our device. The presented microfluidic filtration device for plasma isolation could be integrated into microTAS for point-of-care diagnostics in the near future.

Enzyme Kinetics by Directly Imaging a Porous Silicon Microfluidic Reactor Using Desorption/Ionization on Silicon Mass Spectrometry

Enzyme kinetics were obtained in a porous silicon microfluidic channel by combining an enzyme and substrate droplet, allowing them to react and deposit a small amount of residue on the channel walls, and then analyzing this residue by directly ionizing the channel walls using a matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS) laser source. The porous silicon of the channel walls functions in a manner analogous to the matrix in MALDI-MS, and is referred to as a desorption/ionization on silicon mass spectrometry (DIOS-MS) target when used in this configuration. Mass spectrometry signal intensity of substrate residue correlates with relative concentration, and position in the microchannel correlates with time, thus allowing determination of kinetic parameters. The system is especially suitable for initial reaction velocity determination. This microreactor is broadly applicable to time-resolved kinetic assays as long as at least one substrate or product of the reaction is ionizable by DIOS-MS.

Colloidal self-assembly on internal surfaces of partially sealed microchannels

Self-assembly of micro- and nanoparticles on internal surfaces of micromachined structures can enhance the functionality of a wide range of microfluidic systems. Here, we report experimental investigations of the self-assembly of colloidal microspheres on the sidewalls of partially sealed silicon microfluidic channels. Two different approaches were studied. The first, convective self-assembly, is known to be effective in open-domain microsystems, but was found to result in assemblies with poor uniformity in the partially sealed devices. Real-time video microscopy of the assembly process indicates that these results can be attributed to the prolonged duration of evaporation and the complicated geometry of the evaporation front. In contrast, the second approach, which is a novel combination of sedimentation and hydrodynamic particle removal using a turbulent flow, resulted in the assembly of microparticles on predefined locations on the sidewalls of the microchannels. The important parameters controlling this process are discussed in the context of the literature on hydrodynamic particle removal from flat surfaces.

An extended gate FET-based biosensor integrated with a Si microfluidic channel for detection of protein complexes

In this work, we present an extended gate field effect transistor (EGFET)-based biosensor integrated with a silicon micro-fluidic channel for the electronic detection of streptavidin–biotin protein complexes. The connection between the EGFET and microfluidic system could be achieved with the proposed device, as it offers isolation between the device and solution, compatibility with the integrated circuit (IC) technology and, is applicable to the micro total analysis system (μ-TAS). The device was fabricated on the basis of semiconductor IC fabrication and micro-electro mechanical system (MEMS) technology. Au was used as the extended gate metal to form a self-assembled monolayer (SAM) with thiol. The bindings of the SAM, streptavidin and biotin were detected by measuring the electrical characteristics of the FET device. We also verified the interactions among the SAM, streptavidin, and biotin by using surface plasmon resonance (SPR) measurements. Furthermore, atomic force microscopy (AFM) images of the bio-layers formed on the Au electrode were taken in a solution in order to determine the presence of protein biomolecules with the proposed configuration.

Fabrication of 3-Dimensional Structure of Metal Oxide Semiconductor Field Effect Transistor Embodied in the Convex Corner of the Silicon Micro-Fluidic Channel

As micro-fluidic systems and biochemical detection systems are scaled to smaller dimensions, the realization of small and portable biochemical detection systems has become increasingly important. In this paper, we propose a 3-dimensional structure of a metal oxide semiconductor field-effect transistor(3-D MOSFET) using tetramethyl ammonium hydroxide (TMAH) anisotropic etching, which is a suitable device for combining with a micro-fluidic system. After fabricating a trapezoidal micro-fluidic channel, the 3-D MOSFET embodied in the convex corner of the micro-fluidic channel was fabricated. The length of the gate is about 20 µm and the width is about 9 µm. The depth and top width of the trapezoidal micro-fluidic channel are about 8 µm and 60 µm, respectively. The measured drain saturation current of the 3-D MOSFET was about -22 µA at VGS=-5 V and VDS=-5 V, and the device characteristics exhibit a typical MOSFET behavior. Moreover, a gold layer was used for the MOSFET's gate metal to detect charged biochemical samples using the affinity between gold and thiol.

Selective Surface Modification in Silicon Microfluidic Channels for Micromanipulation of Biological Macromolecules

Interactions between biological macromolecules and micrometer- and sub-micrometer-scale surface structures are directly influenced by the surface wettability, chemical reactivity and surface charge. Understanding these interactions is crucial for developing integrated microsystems for biological and biomedical processing and analysis. We report development of selective surface modification techniques based on microcontact printing and polyelectrolyte adsorption. These techniques were applied to lithographically patterned silicon microfluidic channels and flat silicon substrates to create surface microstructures with contrasting wetting properties and surface charges. These controls enabled us to devise various techniques for controlled loading and processing of biomaterials in the channels. Solutions containing long chain biological macromolecules DNA and microtubules were directly loaded into the microchannels by using a micromanipulator/microinjector system. Structural arrangements of these linear macromolecules, which were probed by using fluorescence and laser scanning confocal microscopy, were found to be quite different from bulk solutions. As expected, the filamentous molecules were observed to align linearly along the channels, with the degree of alignment dependent on channel width as well as the length of the molecule. This molecular alignment, which is induced by both the surface confinement effect and capillary flow during sample loading, may be used to enhance processing of biological materials in silicon biomedical microdevices. It also opens up the possibility of carrying out direct combinatorial structural characterization of proteins in the microchannels utilizing X-ray diffraction, which so far has not been possible.