Search

Here, we introduce a microchip for differential measurements of aqueous samples in twin calorimetric arms with a sub-nL enclosed space. Each arm features a fluidic microchannel located in close proximity to a thin-film resistance thermometer and heater patterned on a low-stress SiN membrane held over a Si cavity with suspension beams. The chip exhibits a rapid response with a thermal time constant of less than 10 ms in atmosphere and a residual thermal conductance below $6{\mu }\text{W}{\cdot }\text{K}^{-1 }$ , one of the lowest reported and accounts for the excellent sensitivity registered in vacuum up to 11 $\text{V}{\cdot }\text{W}^{-1 }$ . These values are in good agreement with those ones predicted by modeling using finite element method, lumped-capacitance analysis, and calorimeter electrothermal circuit simulation together with the measurement system. Long suspension beams in each arm ensure uniform temperature maintained across its membrane as revealed by the fluorescence-based melting curve analysis. We share the specific heat capacity values of water, glycerin, and mineral oil accurately measured by the chip. Lastly, we demonstrate the chip calorimeter utility on the measurement of the photothermal transduction efficiency of plasmonic nanoparticles, which makes our study further unique in expanding the applications of chip calorimeters. [2021-0044]

A dual-channel flow-through microcalorimeter device is presented along with a non-contact precision method of temperature calibration. A microfluidic channel with a volume of ≈550 pL in a spiral layout was fabricated from low-stress nitride suspended over a cavity in a silicon substrate. The thin-film heater and resistive temperature detector (RTD) on the channel were defined by a patterned Ti layer. The device exhibited a rapid thermal response with the following thermal characteristics: a time constant of ≈10.5 ms, a heat conductance of $\approx 152~\mu ~\text{W}\,\cdot ~{\mathrm {K}}^{-{1}} $ and a heat capacitance of $\approx 1.6~\mu \text{J}\,\cdot {\mathrm {K}}^{-{1}} $ on average based on the measurements of nine separate units fabricated on the same wafer. Further, the melting curve analysis (MCA) of a double-stranded DNA was proposed as a non-contact method of microcalorimeter RTD calibration. The method revealed that the measurement by the RTD underestimates the temperature of the channel interior by an amount of nearly 15%, at ≈ 9 mW. At this dissipated power level, the method also revealed a spatial nonuniformity of ≈ ± 0.8 °C across the microcalorimeter. [2020-0173]

SUMMARYThe recently developed single-molecule pulldown (SiMPull) assay by Jain and colleagues is a highly innovative technique but its wide application is hindered by the high technical barrier and time consumption. We report an innovative, agarose microbead-based approach for SiMPull. We used commercially available, pre-surface-functionalized agarose microbeads to capture the protein of interest together with its binding partners specifically from cell extracts and observed these interactions under a microscope at the single-molecule level. Relative to the original method, microbead-based SiMPull is considerably faster, easier to use, and more reproducible and yet provides similar sensitivity and signal-to-noise ratio; specifically, with the new method, sample-preparation time is substantially decreased (from ∼10 to ∼3 h). These crucial features should facilitate wide application of powerful and versatile SiMPull in common biological and clinical laboratories. Notably, by exploiting the simplicity and ultrahigh sensitivity of microbead-based SiMPull, we used this method in the study of rare auditory hair cells for the first time.

Most organs contain interconnected tubular tissues that are one-cell-thick, polarized epithelial monolayers enclosing a fluid-filled lumen. Such tissue organization plays crucial roles in developmental and normal physiology, and the proper functioning of these tissues depends on their regulation by complex biochemical perturbations and equally important, but poorly understood, mechanical perturbations. In this study, by combining micropatterning techniques and atomic force microscopy, we developed a simple in vitro experimental platform for characterizing the mechanical properties of the MDCK II cyst, the simplest model of lumen-enclosing epithelial monolayers. By using this platform, we estimated the elasticity of the cyst monolayer and showed that the presence of a luminal space influences cyst mechanics substantially, which could be attributed to polarization and tissue-level coordination. More interestingly, the results from force-relaxation experiments showed that the cysts also displayed tissue-level poroelastic characteristics that differed slightly from those of single cells. Our study provides the first quantitative findings, to our knowledge, on the tissue-level mechanics of well-polarized epithelial cysts and offers new insights into the interplay between cyst mechanics and cyst physiology. Moreover, our simple platform is a potentially useful tool for enhancing the current understanding of cyst mechanics in health and disease.

Optofluidic devices combining optics and microfluidics have recently attracted attention for biomolecular analysis due to their high detection sensitivity. Here, we show a silicon chip with tubular microchannels buried inside the substrate featuring temperature gradient (∇T) along the microchannel. We set up an optical fluorescence system consisting of a power-modulated laser light source of 470 nm coupled to the microchannel serving as a light guide via optical fiber. Fluorescence was detected on the other side of the microchannel using a photomultiplier tube connected to an optical fiber via a fluorescein isothiocyanate filter. The PMT output was connected to a lock-in amplifier for signal processing. We performed a melting curve analysis of a short dsDNA – SYBR Green I complex with a known melting temperature (TM) in a flow-through configuration without gradient to verify the functionality of the proposed detection system. We then used the segmented flow configuration and measured the fluorescence amplitude of a droplet exposed to ∇T of ≈ 2.31 °C mm−1, determining the heat transfer time as ≈ 554 ms. The proposed platform can be used as a fast and cost-effective system for performing either MCA of dsDNAs or for measuring protein unfolding for drug-screening applications.

Highly localized (point) constrictions featuring a round geometry with ultra-sharp edges in silicon have been demonstrated for the reagent-free continuous-flow rapid mechanical lysis of mammalian cells on a single-cell basis. Silicon point constrictions, robust structures formed by a single-step dry etching process, are arranged in a cascade along microfluidic channels and can effectively rupture cells delivered in a pressure-driven flow. The influence of the constriction size and count on the lysis performance is presented for fibroblasts in reference to total protein, DNA, and intact nuclei levels in the lysates evaluated by biochemical and fluoremetric assays and flow-cytometric analyses. Protein and DNA levels obtained from an eight-constriction treatment match or surpass those from a chemical method. More importantly, many intact nuclei are found in the lysates with a relatively high nuclei-isolation efficiency from a four-constriction treatment. Point constrictions and their role in rapid reagent-free disruption of the plasma membrane could have implications for integrated sample preparation in future lab-on-a-chip systems.

Here, we present an experimental demonstration of slowing DNA translocation across a nanochannel by modulating the channel surface charge through an externally applied gate bias. The experiments were performed on a nanofluidic field-effect transistor, which is a monolithic integrated platform featuring a 50 nm-diameter in-plane alumina nanocapillary whose entire length is surrounded by a gate electrode. The field-effect transistor behavior was validated on the gating of ionic conductance and protein transport. The gating of DNA translocation was subsequently studied by measuring discrete current dips associated with single λ-DNA translocation events under a source-to-drain bias of 1 V. The translocation speeds under various gate bias conditions were extracted by fitting event histograms of the measured translocation time to the first passage time distributions obtained from a simple 1D biased diffusion model. A positive gate bias was observed to slow the translocation of single λ-DNA chains markedly; the translocation speed was reduced by an order of magnitude from 18.4 mm/s obtained under a floating gate down to 1.33 mm/s under a positive gate bias of 9 V. Therefore, a dynamic and flexible regulation of the DNA translocation speed, which is vital for single-molecule sequencing, can be achieved on this device by simply tuning the gate bias. The device is realized in a conventional semiconductor microfabrication process without the requirement of advanced lithography, and can be potentially further developed into a compact electronic single-molecule sequencer.

Microfluidic devices typically require complex shapes such as funnels, spirals, splitters, channels with different widths, or customized objects of arbitrary complexity with a smooth transition between these elements. Device layouts are generally designed by software developed for the design of integrated circuits or by general computer-aided design drawing tools. Both methods have their limitations, making these tasks time consuming. Here, a script-based, time-effective method to generate the layout of various microfluidic chips with complex geometries is presented. The present work uses the nanolithography toolbox (NT), a platform-independent software package, which employs parameterized fundamental blocks (cells) to create microscale and nanoscale structures. In order to demonstrate the functionality and efficiency of the NT, a few classical microfluidic devices were designed using the NT and then fabricated in glass/silicon using standard microfabrication techniques and in poly(dimethylsiloxane) using soft lithography as well as more complex techniques used for flow-through calorimetry. In addition, the functionality of a few of the fabricated devices was tested. The powerful method proposed allows the creation of microfluidic devices with complex layouts in an easy way, simplifying the design process and improving design efficiency. Thus, it holds great potential for broad applications in microfluidic device design.

Infectious diseases, such as the most recent case of COVID-19, have brought the prospect of point-of-care (POC) diagnostic tests into the spotlight. A rapid, accurate, low-cost, and easy-to-use test in the field could stop epidemics before they develop into full-blown pandemics. Unfortunately, despite all the advances, it still does not exist. Here, we critically review the limited number of prototypes demonstrated to date that is based on a polymerase chain reaction (PCR) and has come close to fulfilling this vision. We summarize the requirements for the POC-PCR tests and then go on to discuss the PCR product-detection methods, the integration of their functional components, the potential applications, and other practical issues related to the implementation of lab-on-a-chip technologies. We conclude our review with a discussion of the latest findings on nucleic acid-based diagnosis., Highlights • Recently there is a boom in development of portable microfluidic based system for SARS-CoV-2 molecular diagnostics. • Most of those techniques approved by US FDA is based on a reverse transcription polymerase chain reaction (RT-PCR). • Drawback of the RT-PCR methods such as sample preparation to remove PCR inhibitors and perform sample preconcentration.

This paper describes the design, the fabrication, and the characterization of an interdigitated 3-D silicon (Si) ring microelectrodes for dielectrophoretic (DEP) manipulation of particles. The 3-D microelectrodes are derived from a high-aspect-ratio comb structure etched in a doped single crystal Si on an insulating dielectric (silicon-on-insulator). Fingers of the comb are evolved into ring microelectrodes once perforated with a linear array of well-defined round lateral constrictions. This is achieved by the segmented finger layout and the Si dry release strategy borrowed from inertial microelectromechanical systems. The fingers and their interspaces are sealed with a cover layer forming a microfluidic flow chamber surrounded by 3-D microelectrodes and accessible via single inlet/outlet. The functionality of the device has been verified on 2- and 10-μm polystyrene microspheres in pressure-driven flow through the ring microelectrodes at 3.3 μL/min effectively focusing them into streams or trapping them around the fingers at moderate voltage levels (20-40 Vpp).

A simple method for evaluating chaotic advection in slug micromixing is reported in this paper. We consider a slug moving in a slit microchannel ( w ⪢ h ) and flow field in a plane far from the boundary walls is modelled as a two-dimensional low-Reynolds-number flow (Stokes flow). Analytical solution for normalised velocity field in the slug is derived. The two-dimensional analytical solution is compared with the two-dimensional slice from the three-dimensional numerical solution of the slug velocity field. Boundary conditions mimicking the motion of the slugs in microchannel geometries, in Lagrangian frame of reference, is used to track the passive tracer particles using Lagrangian particle tracking method. Poincare sections and dye advection patterns are used to analyse chaotic advection of passive tracer particles using statistical concepts such as ‘variance’, ‘Shannon entrophy’ and ‘complete spatial randomness’. Results for boundary conditions mimicking constant-velocity straight-channel flow, constant-velocity normal-meandering channel flow are compared. A method for finding new channel geometries which enhance chaotic mixing is also proposed.

This article reports a design that reliably adds reagents into droplets by exploiting the physics of fluid flow at a T-junction in the microchannel. An expanded section right after the T-junction enhances merging of a stream with a droplet, eliminates the drawbacks such as extra droplet formation and long mixing time. The expanded section reduces the pressure buildup at the T-junction and minimizes the tendency to form extra droplets; plays the role in creating low Laplace pressure jump across the interface of the droplet forming from the T-junction which reduces the probability of forming extra droplet in the merging process; provides space for droplet coalescence if there is an extra droplet due to droplet break-up before merging. In this design, after merging, the reactants are in axial arrangement inside the droplets which lead to faster mixing. Reliable addition of reagent to the droplets happens for the combination of flow rates in a broad range from 25 to 250 μl/h, for both DI water (Q DI) and fluorescent (Q fluo) streams.

A fixed-grid approach for modeling the motion of a particle-encapsulated droplet carried by a pressure-driven immiscible carrier fluid in a microchannel is presented. Three phases (the carrier fluid, the droplet, and the particle) and two different moving boundaries (the droplet–carrier fluid and droplet–particle interfaces) are involved. This is a moving-boundaries problem with the motion of the three phases strongly coupled. In the present article, the particle is assumed to be a fluid of high viscosity and constrained to move with rigid body motion. A combined formulation using one set of governing equations to treat the three phases is employed. The droplet–carrier fluid interface is represented and evolved using a level-set method with a mass-correction scheme. Surface tension is modeled using the continuum surface force model. An additional signed distance function is employed to define the droplet–particle interface. Its evolution is determined from the particle motion governed by the Newton-Euler equations. The governing equations are solved numerically using a finite-volume method on a fixed Cartesian grid. For demonstration purposes, the flows of particle-encapsulated droplets through a constricted microchannel and through a microchannel system are presented. Accepted version

This paper reports experimental investigations on the droplet formation and size manipulation of deionized water (DIW) and nanofluids in a microfluidic T-junction at different temperatures. Investigations of the effect of microchannel depths on the droplet formation process showed that the smaller the depth of the channel the larger the increase of droplet size with temperature. Sample nanofluids were prepared by dispersing 0.1 volume percentage of titanium dioxide (TiO2) nanoparticles of 15 nm and 10 nm × 40 nm in DIW for their droplet formation experiments. The heater temperature also affects the droplet formation process. Present results demonstrate that nanofluids exhibit different characteristics in droplet formation with the temperature. Addition of spherical-shaped TiO2 (15 nm) nanoparticles in DIW results in much smaller droplet size compared to the cylindrical-shaped TiO2 (10 nm × 40 nm) nanoparticles. Besides changing the interfacial properties of based fluid, nanoparticles can influence the droplet formation of nanofluids by introducing interfacial slip at the interface. Other than nanofluid with cylindrical-shaped nanoparticles, the droplet size was found to increase with increasing temperature. Accepted version

Detailed experimental and simulation studies are performed and presented to further substantiate the previously reported high-performance flow-focusing geometry for droplet generation. In this geometry, water-in-oil droplets are formed through a three-dimensional (3D) circular orifice directly integrated inside a silicon microchannel. The geometry ensures controlled breakup of droplets for a wide range of flow rates. Simulations are provided using computational fluid dynamics software to elucidate the flow behavior nearby the 3D circular orifice. In addition, experimental results on the droplet generation characteristics are obtained both from the 3D circular constriction as well as quasi-2D (2D) rectangular constriction that are typically used in flow-focusing devices. Direct comparison of these results further supports the claim that droplets formed by the 3D circular orifice show noticeably increased sensitivity against the flow rate of the continuous oil-phase both in droplet size and generation frequency.

The extracellular matrix (ECM) exhibits tissue-specific topography and composition and plays a crucial role in initiating the biochemical and biomechanical signaling required for organizing cells into distinct tissues during development. How single cells assemble into structures featuring specific shapes in response to external cues is poorly understood. We examined the effect of substrate nanotopography on the morphogenesis of several types of epithelial cells and found that in response to the topography, Calu-3 and MDCK-II cells formed organoids that closely resemble their morphology in vivo. This finding represents the first demonstration that substrate nanotopography, one of the first physical cues detected by cells, can by itself induce epithelial tissue-like organization. Our results provide insights, in terms of a new aspect of ECM topography, into the design of future tissue-engineering systems and the study of mechanosignaling in the epithelium during normal development and tumor progression.

The ''gold'' standard in the study of ionic currents across biological membranes is the Patch Clamp method. However, this is a slow, labor and skill intensive process. High throughput patch clamp devices are mainly chip-based. A major challenge in these miniaturized devices is the low rate of ''Gigaseal'' formation which is critical in the study of Single Channel effect. In a conventional patch clamp, a pipette moves and patches a fixed cell (cell-adhered patch) which is grown on the bottom of a Petri dish. In the chip-based case, the cells are in suspension and move towards the fixed patch clamp sites (cell-suspended patch). In this study, using the proven conventional patch clamp setup, we investigated the effect of the differences in the cell configurations between the convention patch clamp and cell-based patch clamp. It is shown that adhered cells (as used in the conventional setup) have a much higher rate of gigaseal formation as compared to the cells in suspension (as used in chip-based devices). We postulate that the arrangement of the cytoskeleton within the cell plays a major part in the formation of the gigaseal.

Oxygen plasma treatment has been used extensively to bond polydimethyl siloxane to polydimethyl siloxane or glass in the rapid prototyping of microfluidic devices. This study aimed to improve the bonding quality of polydimethyl siloxane to passivated silicon using oxygen plasma treatment, and also to evaluate the bonding quality. Four types of passivated silicon were used: phosphosilicate glass, undoped silicate glass, silicon nitride and thermally grown silicon dioxide. Bonding strength was evaluated qualitatively and quantitatively using manual peel and mechanical shear tests respectively. Through peel tests we found that the lowering of plasma pressure from 500 to 30 mTorr and using a plasma power between 20 to 60 W helped to improve the bond quality for the first three types of passivation. Detailed analysis and discussion were conducted to explain the discrepancy between the bonding strength results and peeling results. Our results suggested that polydimethyl siloxane can be effectively bonded to passivated silicon, just as to polydimethyl siloxane or glass.

We report on reversible electroporation of cells in a flow-through microfluidic device, whereby the required electric field is delivered through a set of integrated microcapillaries between a centre stream of cells and side streams of liquid electrolytes. The electrolytes are applied with a sine wave voltage and cells flow by the microcapillary openings encounter a burst of ac field with a duration and strength determined by their average speed and spatial proximity to the microcapillary openings, respectively. Effectiveness of the approach is presented through numerical simulations and empirical results on electroporation efficiency and cell viability against various flow rates (exposure time to the field) as well as frequencies and root-mean-square (rms) intensities of the field. High frequencies (80–400 kHz) and high intensities (e.g., 1.6 kV/cm, rms) are identified with increased electroporation efficiency 61% and viability 86% on average. These results suggest that the device demonstrated here with a simple design and robust operation offers a viable platform for flow-through electroporation.

We report the label-free enumeration of human colorectal-carcinoma cells from blood lymphocytes by using interdigitated ring-array microelectrodes; this enumeration was based on the dielectrophoretic selection of cells. Because of the novel design of the device, a continuous flow of cells is uniformly distributed into parallel streams through 300 rings (~40 μm in diameter each) that are integrated into the electrode digits. Using this array, 82% of cancer cells were recovered and 99% of blood lymphocytes were removed. Most of the cancer cells recovered were viable (94%) and could be cultivated for8 days, during which period they retained their normal cell morphology and proliferation rates. The recovery rate correlated closely with cancer-cell loadings in spiked samples and this relationship was linear over a range of at least 2 orders of magnitude. Importantly, because of the 3D structure of the rings, these results were obtained at a high cell-loading concentration (10(7)cells/mL). The rings could be further optimized for use in accurate label-free identification and measurement of circulating tumor cells in cancer research and disease management.

Recent success of microelectromechanical systems (MEMS) in projection displays have raised similar expectation for an efficient, low power, affordable, full-page and pneumatic tactile display. Such design has not been achieved by the conventional technology but could bring significant improvement to current refreshable Braille displays. This paper demonstrates a novel bulk-micromachined electrostatic microvalve suitable for a pneumatic tactile display. The microvalve, a silicon perforated diaphragm juxtaposed to a silicon inlet orifice, requires relatively low closing voltage against a large supply differential pressure and flow rate, i.e., 72.9 V-rms for 19.3 kPa and 85 mi/min. Such an attractive characteristic is due to its unique curved-compliant structure that has, unlike other electrostatic microvalves, no tolerance for any initial air gap between its electrodes. As a design tool, a mechanical model of the microvalve is introduced based on the lubrication theory and large plate deflection theory. The model is established on a steady-state coupled field problem of fluid-solid mechanics. Reynolds and von-Karman equations were simultaneously solved for the microvalve geometry by finite difference approximation and double Fourier series expansion. The results of the model and experiments are compared and found to be in good agreement with a relative error less than 10%.

A label-free method of quantifying nucleic acids in polymerase chain reaction (PCR) is described and could be the basis for miniaturized devices that can amplify and detect target nucleic acids in real time. The method takes advantage of ionic current rectification effect discovered in nanofluidic channels exhibiting a broken symmetry in electrochemical potential – nanofluidic diodes. Nanofluidic diodes are prototyped here on nanopipettes readily pulled from individual thin-walled glass capillaries for a proof of concept demonstration yet the basic concept would be applicable to ionic rectifiers constructed through other means. When a nanopipette modified in the tip region with cationic polyelectrolytes is presented with an unpurified PCR product, the tip surface electrostatically interacts with the amplicons and modulates its ionic rectification direction in response to the intrinsic charge of those adsorbed. Modulations are gradual and correlate well with the mass concentration of the amplicons above 2.5 ng/μL, rather than their sizes, with adequate discrimination against the background. Moreover, the tip surface, following a measurement, is regenerated through a layer-by-layer assembly of cationic polyelectrolytes and amplicons. The regenerated tips are capable of measuring distinct mass concentrations without signs of noticeable degradation in sensitivity. Further, the tips are shown capable of reproducing the amplification curve of real-time PCR through sequential steps of surface regeneration and simple electrical readout during the intermediate reaction stages. This suggests that nanopipettes as nanofluidic diodes are at a capacity to be employed for monitoring the PCR progress.

We demonstrate a new method of fabricating in-plane cylindrical glass nanocapillaries (1 μm). These nanocapillaries are self-enclosed optically transparent and highly regular over large areas. Our method involves structuring μm-scale rectangular trenches in silicon, sealing the trenches into enclosed triangular channels by depositing phosphosilicate glass, and then transforming the channels into cylindrical capillaries through shape transformation by the reflow of annealed glass layer. Extended anneal has the structures shrunk into nanocapillaries preserving their cylindrical shape. Nanocapillaries ∼50 nm in diameter and effective stretching of digested λ-phage DNA in them are demonstrated.

We demonstrate monolithic integration of fine cylindrical glass microcapillaries (diameter ∼1 μm) on silicon and evaluate their performance for electrophoretic separation of biomolecules. Such microcapillaries are achieved through thermal reflow of a glass layer on microstructured silicon whereby slender voids are moulded into cylindrical tubes. The process allows self-enclosed microcapillaries with a uniform profile. A simplified method is also described to integrate the microcapillaries with a sample-injection cross without the requirement of glass etching. The 10-mm-long microcapillaries sustain field intensities up to 90 kV/m and limit the temperature excursions due to Joule heating to a few degrees Celsius only.

The isolation of circulating tumor cells (CTCs) using microfluidics is attractive as the flow conditions can be accurately manipulated to achieve an efficient separation. CTCs are rare events within the peripheral blood of metastatic cancer patients which makes them hard to detect. The presence of CTCs is likely to indicate the severity of the disease and increasing evidences show its use for prognostic and treatment monitoring purposes. We demonstrated an effective separation using a microfluidic device to utilize the unique differences in size and deformability of cancer cells to blood cells. Using physical structures placed in the path of blood specimens in a microchannel, CTCs which are generally larger and stiffer are retained while most blood constituents are removed. The placements of the structures are optimized by computational analysis to enhance the isolation efficiency. With blood specimens from metastatic lung cancer patients, we confirmed the successful detection of CTCs. The operations for processing blood are straightforward and permit multiplexing of the microdevices to concurrently work with different samples. The microfluidic device is optically transparent which makes it simple to be integrated to existing laboratory microscopes and immunofluorescence staining can be done in situ to distinguish cancer cells from hematopoietic cells. This also minimizes the use of expensive staining reagents, given the small size of the microdevice. Identification of CTCs will aid in the detection of malignancy and disease stage as well as understanding the phenotypic and genotypic expressions of cancer cells.

We have designed, fabricated and characterized poly(dimethylsiloxane) (PDMS) single-mode rib waveguides. PDMS was chosen specifically for the core and cladding. Combined with the soft lithography fabrication techniques, it enables an easy integration of microoptical components for lab-on-a-chip systems. The refractive index contrast, Δ of 0.07% between the core and cladding for single-mode propagation was achieved by modifying the properties of the same base material. Alternatively, a higher refractive index contrast, Δ of 1.18% was shown by using PDMS materials from two different manufacturers. The fabricated rib waveguides were characterized for mode profile characteristics and confirmed the excitation of the fundamental mode of the waveguide. The propagation loss of the single-mode rib waveguide was characterized using the cutback measurement method at a wavelength of 635 nm and found to be 0.48 dB/cm for Δ of 0.07% and 0.20 dB/cm for Δ of 1.18%. Y-branch splitter of PDMS single-mode rib waveguide was further demonstrated.

The ability to precisely control the motion of droplets is essential in droplet-based microfluidics. It serves as the basis for various droplet-based devices. This paper presents a thermal control technique for microdroplets at a bifurcation. Control was achieved using an integrated microheater that simultaneously induces a reduction in fluidic resistance and thermocapillarity. The temperature of the heater was monitored by an integrated temperature sensor. At a bifurcation with symmetric branches, a droplet can be split into two daughter droplets of controllable sizes or entirely switched into a desired branch. The physics of this phenomenon was investigated with the help of a numerical model. Splitting and switching were demonstrated within an operational temperature range 25–38 °C. The relatively low operational temperature range allows this technique to be used for droplets containing biological samples. The present control concept is not limited to bifurcations, but can be employed in other geometries. Accepted version

The authors used thermally induced surface tension gradients to manipulate aqueous droplets in microchannels. Control of the droplet breakup process was demonstrated. Droplet sorting can be achieved with temperatures above a critical value. Numerical simulation using a two-dimensional model agrees qualitatively well with the experimental results. The used control temperature of less than 55 °C shows that this active control concept is suitable for biochemical applications. Thermal control promises to be a simple and effective manipulation method for droplet-based lab on a chip. Published version

We have designed, fabricated and characterized poly(dimethylsiloxane) (PDMS) arrayed waveguide grating (AWG) with four-channel output for operation in the visible light wavelength range. The PDMS AWG was realized based on the single-mode PDMS rib waveguide. The device was designed for 1 nm channel spacing with the wavelength ranging from 639 to 644 nm. The measured insertion loss is 11.4 dB at the peak transmission spectrum and the adjacent crosstalk is less than -16 dB. The AWG device occupies an area of 7.5 × 15 mm(2). PDMS AWG has the potential for integration with microfluidics in a monolithic PDMS lab-on-a-chip device for visible light spectroscopy applications.

This paper reports the formation and manipulation of ferrofluid droplets at a microfluidic T-junction in the presence of a permanent magnetic field. A small circular permanent magnet with a diameter of 3 mm is used to control the size of the ferrofluid droplets within a microfluidic device. In the absence of a magnetic field, the size of the ferrofluid droplets decreases linearly with the increase of the flow rate of the continuous phase. In the presence of a magnetic field, the size of the droplets depends on the magnetic field strength, magnetic field gradient and the magnetization of the ferrofluid. The magnetic field strength is adjusted in our experiment by the location of the magnet. The induced attractive magnetic force affects the droplet formation process leading to the change in the size of the formed droplets. Experimental observation also shows that the relative change in the size of the droplet depends on the flow rate of the continuous phase. Furthermore, the paper compares the evolving shape of the ferrofluid droplet during the formation process with and without the magnetic field.

This paper reports experimental investigations on the droplet formation of deionized water and a nanofluid in a heat-induced microfluidic flow focusing device. Besides the effect of temperature, the effects of nanoparticle suspension (nanofluid) and the flow rate of aqueous fluid on the droplet formation and size manipulation were studied. At constant flow rates of the two liquids, three different droplet breakup regimes were observed and their transition capillary numbers as well as temperatures were identified. The heat generated by an integrated microheater changes the droplet formation process. Increasing the temperature enlarges the size of the droplets significantly. These results also demonstrate that the titanium oxide (15 nm)/deionized water-based nanofluid exhibits similar characteristics in droplet formation at different temperatures and any small change in the flow rate of this nanofluid has little impact on the size of the droplets formed in a flow focusing geometry. Accepted version

Precise dispensing of microdroplets is an important process for droplet-based microfluidics. The droplet formation by shear force between two immiscible fluids depends on their flow rates, the viscosities, and the interfacial tension. In this letter, the authors report the use of integrated microheater and temperature sensor for controlling the droplet formation process. The technique exploits the dependency on temperature of viscosities and interfacial tension. Using a relatively low heating temperature ranging from 25 to 70 °C, the droplet diameter can be adjusted to over two times of its original value. The relatively low temperature range makes sure that this concept is applicable for droplets containing biological samples Published version

Significant efforts have been targeted towards developing a droplet-based microfluidic system and understanding the droplet formation process and the physics behind it and yet the underlying physics of the droplet formation in terms of evolution of pressures in both the continuous phase and dispersed phase has received less attention over the years and is not understood clearly. A numerical investigation on the mechanism of droplet formation in a microfluidic T-junction has been conducted and validated against the experimental flow visualisation. From the computational results it is shown that the pressure profile of the dispersed phase and the continuous phase in the squeezing regime changes as the droplet break-up process proceeds. New insights on the droplet break-up process such as the minimum pressure difference between the continuous phase and the dispersed phase happens at the last moment of the the droplet break-up and not during the second and third stage of the droplet formation mechanism in the squeezing regime have been identified. As a next step in the analysis, reagent addition to microfluidic droplets is a fundamental operation in high-throughput screenings. Adding precise amount of reagents to droplets poses difficulties and many of the available designs use complicated structures and fabrication methods. A design that reliably adds reagents into droplets by exploiting the physics of fluid flow at an expanded section right after the T-junction which enhances merging of a stream with a droplet, eliminates the drawbacks such as extra droplet formation and long mixing time is demonstrated. Experimental results show that the expanded section minimizes the tendency to form extra droplets; the reactants are in axial arrangement inside the droplets which leads to faster mixing; reliable addition of reagent to the droplets happens for the combination of flow rates in a broad range of both substrate and reagent streams. To understand the physics behind the reliable operation of reagent addition, a numerical investigation using VOF model has been conducted. The flow field and the pressure measurements show that when an expanded section is used, the dynamics of droplet formation mechanism undergoes a significant change and is dominated by the combination of both shear stress and pressure buildup-based droplet breakup from a pure pressured buildup-based droplet breakup in the squeezing regime; and the expanded section plays the role in creating low Laplace pressure jump across the interface of the droplet forming from the T-junction which reduces the probability of forming extra droplet in the merging process. DOCTOR OF PHILOSOPHY (MAE)

In this thesis, PDMS-based AWG microspectrometer for LOC application was demonstrated by foremost developing planar waveguide in PDMS material. The development of planar waveguide focused primarily in design and fabrication of novel PDMS waveguide with single-mode propagation as the basic building block for complex devices. By selecting the appropriate geometrical parameters, single-mode propagation can be generated even in a large cross section PDMS rib waveguide (> 5 μm). The fabrication of PDMS single-mode waveguide involved precise controlled of the slab and rib height to the accuracy of ±0.1 μm as well as the modification of the refractive index from 1.408 to 1.429. The characterization ATTENTION: The Singapore Copyright Act applies to the use of this document. Nanyang Technological University Library VIII of the PDMS waveguide corroborated single-mode propagation at the wavelength of 635 nm with the propagation loss measured to be 0.48 dB/cm for low refractive index contrast waveguides (Δ=0.07%) and 0.2 dB/cm for high refractive index contrast waveguides (Δ=1.18%). DOCTOR OF PHILOSOPHY (EEE)