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Topical Collection "Lab-on-a-Chip"

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A topical collection in Micromachines (ISSN 2072-666X).

Editor

Collection Editor
Prof. Dr. Jeong-Bong Lee (Website)

Erik Jonsson School of Engineering and Computer Science, RL 10 The University of Texas at Dallas, 800 W. Campbell Rd., Richardson, TX 75080, USA
Phone: 972-883-2893
Fax: +1 972 883 6839
Interests: biomedical MEMS; RF MEMS; nanophotonics; MEMS packaging

Topical Collection Information

Dear Colleagues,

Lab-on-a-chip (LOC) stands for the vision to integrate all necessary functions to perform, e.g., a chemical analysis, a biochemical assay or even the organic synthesis of new chemicals on a single miniaturized device, built from a planar substrate (silicon, glass, ceramics, polymers, ...) using micro and nanofabrication techniques. Its promises include fast analyses and high throughput, minute consumption of sample and resources, ruggedness, ease-of-use and portability. LOC is a very cross-disciplinary research field, which requires input from engineers, chemists, physicists, biologists and medical experts, not least because of the technological bricks that have to come together to realize lab-on-a-chip systems: fabrication, materials, surface treatments, microfluidics, sample preparation, separation techniques, detection approaches, and much more. Beyond ongoing efforts to refine the toolbox of LOC and to improve the understanding of fundamental aspects (e.g., transport in nanofluidic channels), applications of LOC can be found within medical diagnostics, environmental monitoring, food quality control, early detection of warfare agents, and drug development. This collection will highlight recent developments within LOC technology as well as examples of state-of-the-art applications.

Prof. Dr. Jeong-Bong (JB) Lee
Collection Editor

Manuscript Submission Information

Manuscripts for the topical collection can be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on this website. The topical collection considers regular research articles, short communications and review articles. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1000 CHF (Swiss Francs).

Published Papers (21 papers)

2016

Jump to: 2015, 2014, 2013, 2011

Open AccessArticle Integration of an Optical Ring Resonator Biosensor into a Self-Contained Microfluidic Cartridge with Active, Single-Shot Micropumps
Micromachines 2016, 7(9), 153; doi:10.3390/mi7090153
Received: 4 August 2016 / Revised: 24 August 2016 / Accepted: 29 August 2016 / Published: 13 September 2016
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Abstract
While there have been huge advances in the field of biosensors during the last decade, their integration into a microfluidic environment avoiding external tubing and pumping is still neglected. Herein, we show a new microfluidic design that integrates multiple reservoirs for reagent [...] Read more.
While there have been huge advances in the field of biosensors during the last decade, their integration into a microfluidic environment avoiding external tubing and pumping is still neglected. Herein, we show a new microfluidic design that integrates multiple reservoirs for reagent storage and single-use electrochemical pumps for time-controlled delivery of the liquids. The cartridge has been tested and validated with a silicon nitride-based photonic biosensor incorporating multiple optical ring resonators as sensing elements and an immunoassay as a potential target application. Based on experimental results obtained with a demonstration model, subcomponents were designed and existing protocols were adapted. The newly-designed microfluidic cartridges and photonic sensors were separately characterized on a technical basis and performed well. Afterwards, the sensor was functionalized for a protein detection. The microfluidic cartridge was loaded with the necessary assay reagents. The integrated pumps were programmed to drive the single process steps of an immunoassay. The prototype worked selectively, but only with a low sensitivity. Further work must be carried out to optimize biofunctionalization of the optical ring resonators and to have a more suitable flow velocity progression to enhance the system’s reproducibility. Full article
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Open AccessArticle Investigation of the Influence of Glucose Concentration on Cancer Cells by Using a Microfluidic Gradient Generator without the Induction of Large Shear Stress
Micromachines 2016, 7(9), 155; doi:10.3390/mi7090155
Received: 20 July 2016 / Revised: 23 August 2016 / Accepted: 24 August 2016 / Published: 1 September 2016
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Abstract
A microfluidic device capable of precise chemical control is helpful to mimic tumor microenvironments in vitro, which are closely associated with malignant progression, including metastasis. Cancer cells under a concentration gradient of oxygen and other sustenance materials inside a tumor in vivo [...] Read more.
A microfluidic device capable of precise chemical control is helpful to mimic tumor microenvironments in vitro, which are closely associated with malignant progression, including metastasis. Cancer cells under a concentration gradient of oxygen and other sustenance materials inside a tumor in vivo have recently been reported to increase the probability of metastasis. The influence of glucose concentration on cancer cells has not been measured well, whereas that of oxygen concentration has been thoroughly examined using microfluidic devices. This is because glucose concentrations can be controlled using microfluidic concentration gradient generators, which trade off temporal stability of the glucose concentration and shear stress on the cells; by contrast, oxygen concentration can be easily controlled without microfluidic device-induced shear stresses. To study cell division and migration responses as a function of glucose concentration, we developed a microfluidic device to observe cell behaviors under various chemical conditions. The device has small-cross-section microchannels for generating a concentration gradient and a large-cross-section chamber for cell culture. With this design, the device can achieve both a cell culture with sufficiently low shear stress on cell activity and a stable glucose concentration gradient. Experiments revealed that a low glucose concentration increased the total migration length of HeLa cells and that HeLa cells under a glucose concentration gradient exhibit random motion rather than chemotaxis. Full article
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Open AccessArticle Microstructure-Enhanced Liquid–Liquid Extraction in a Real-Time Fluorescence Detection Microfluidic Chip
Micromachines 2016, 7(3), 46; doi:10.3390/mi7030046
Received: 25 January 2016 / Revised: 27 February 2016 / Accepted: 8 March 2016 / Published: 10 March 2016
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Abstract
Microfluidic system is widely employed in the detection of environmental contaminants and biological specimens. One of the critical issues which limits the applications of microfluidic chips is the limit of detection of trace specimens. Liquid–liquid extraction is of great importance in the [...] Read more.
Microfluidic system is widely employed in the detection of environmental contaminants and biological specimens. One of the critical issues which limits the applications of microfluidic chips is the limit of detection of trace specimens. Liquid–liquid extraction is of great importance in the preprocessing in microfluidic devices. In this paper, we developed a real-time fluorescence detection microfluidic chip combined with a microstructure-enhanced liquid–liquid laminar extraction technique, which concentrated the trace compound and realized real-time monitoring. Auxiliary microstructures integrated in the microfluidic chip were applied to increase the extraction efficiency, which was proved by the FEM (finite element method) simulation as well. A common fluorescence probe, Rhodamine 6G (Rh6g), was used in the experiment to demonstrate the performance of the microfluidic system. It revealed that the liquid–liquid laminar extraction combined with auxiliary microstructures of a cross shape was an effective method for enrichment. The efficiency of microstructure-enhanced liquid–liquid extraction was increased by 350% compared to the traditional laminar flow extraction. Full article
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Open AccessArticle Mathematical Modelling and Simulation Research of Thermal Engraving Technology Based on PMMA Material
Micromachines 2016, 7(3), 37; doi:10.3390/mi7030037
Received: 30 November 2015 / Revised: 17 February 2016 / Accepted: 22 February 2016 / Published: 26 February 2016
Cited by 1 | PDF Full-text (2115 KB) | HTML Full-text | XML Full-text
Abstract
We proposed a thermal engraving technology based on heat transfer theory and polymer rheology in microfluidic field. Then, we established a 3D model of the thermal engraving process based on polymethyl methacrylate (PMMA) material. We could employ the model to analyze the [...] Read more.
We proposed a thermal engraving technology based on heat transfer theory and polymer rheology in microfluidic field. Then, we established a 3D model of the thermal engraving process based on polymethyl methacrylate (PMMA) material. We could employ the model to analyze the influence of temperature and speed on microchannel processing through the finite element simulation. Thus, we gained the optimal processing parameters. The orthogonal experiments were carried out within the parameter ranges obtained by the simulation results. Finally, we fabricated the smooth microchannel, the average roughness of which was 0.3 μm, by using the optimal parameters. Furthermore, we examined the surface morphology and wettability. Our work provides a convenient technological support for a fast, low-cost, and large-scale manufacturing method of microfluidic chips. Full article
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Open AccessArticle Microfluidic-Based Droplet and Cell Manipulations Using Artificial Bacterial Flagella
Micromachines 2016, 7(2), 25; doi:10.3390/mi7020025
Received: 4 January 2016 / Revised: 2 February 2016 / Accepted: 3 February 2016 / Published: 8 February 2016
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Abstract
Herein, we assess the functionality of magnetic helical microswimmers as basic tools for the manipulation of soft materials, including microdroplets and single cells. Their ability to perform a range of unit operations is evaluated and the operational challenges associated with their use [...] Read more.
Herein, we assess the functionality of magnetic helical microswimmers as basic tools for the manipulation of soft materials, including microdroplets and single cells. Their ability to perform a range of unit operations is evaluated and the operational challenges associated with their use are established. In addition, we also report on interactions observed between the head of such helical swimmers and the boundaries of droplets and cells and discuss the possibilities of assembling an artificial swimming microorganism or a motorized cell. Full article
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Open AccessReview Thermocapillarity in Microfluidics—A Review
Micromachines 2016, 7(1), 13; doi:10.3390/mi7010013
Received: 1 November 2015 / Revised: 1 January 2016 / Accepted: 8 January 2016 / Published: 21 January 2016
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Abstract
This paper reviews the past and recent studies on thermocapillarity in relation to microfluidics. The role of thermocapillarity as the change of surface tension due to temperature gradient in developing Marangoni flow in liquid films and conclusively bubble and drop actuation is [...] Read more.
This paper reviews the past and recent studies on thermocapillarity in relation to microfluidics. The role of thermocapillarity as the change of surface tension due to temperature gradient in developing Marangoni flow in liquid films and conclusively bubble and drop actuation is discussed. The thermocapillary-driven mass transfer (the so-called Benard-Marangoni effect) can be observed in liquid films, reservoirs, bubbles and droplets that are subject to the temperature gradient. Since the contribution of a surface tension-driven flow becomes more prominent when the scale becomes smaller as compared to a pressure-driven flow, microfluidic applications based on thermocapillary effect are gaining attentions recently. The effect of thermocapillarity on the flow pattern inside liquid films is the initial focus of this review. Analysis of the relation between evaporation and thermocapillary instability approves the effect of Marangoni flow on flow field inside the drop and its evaporation rate. The effect of thermocapillary on producing Marangoni flow inside drops and liquid films, leads to actuation of drops and bubbles due to the drag at the interface, mass conservation, and also gravity and buoyancy in vertical motion. This motion can happen inside microchannels with a closed multiphase medium, on the solid substrate as in solid/liquid interaction, or on top of a carrier liquid film in open microfluidic systems. Various thermocapillary-based microfluidic devices have been proposed and developed for different purposes such as actuation, sensing, trapping, sorting, mixing, chemical reaction, and biological assays throughout the years. A list of the thermocapillary based microfluidic devices along with their characteristics, configurations, limitations, and improvements are presented in this review. Full article
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Open AccessArticle Temperature Sensing in Modular Microfluidic Architectures
Micromachines 2016, 7(1), 11; doi:10.3390/mi7010011
Received: 8 December 2015 / Revised: 28 December 2015 / Accepted: 6 January 2016 / Published: 18 January 2016
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Abstract
A discrete microfluidic element with integrated thermal sensor was fabricated and demonstrated as an effective probe for process monitoring and prototyping. Elements were constructed using stereolithography and market-available glass-bodied thermistors within the modular, standardized framework of previous discrete microfluidic elements demonstrated in [...] Read more.
A discrete microfluidic element with integrated thermal sensor was fabricated and demonstrated as an effective probe for process monitoring and prototyping. Elements were constructed using stereolithography and market-available glass-bodied thermistors within the modular, standardized framework of previous discrete microfluidic elements demonstrated in the literature. Flow rate-dependent response due to sensor self-heating and microchannel heating and cooling was characterized and shown to be linear in typical laboratory conditions. An acid-base neutralization reaction was performed in a continuous flow setting to demonstrate applicability in process management: the ratio of solution flow rates was varied to locate the equivalence point in a titration, closely matching expected results. This element potentially enables complex, three-dimensional microfluidic architectures with real-time temperature feedback and flow rate sensing, without application specificity or restriction to planar channel routing formats. Full article
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2015

Jump to: 2016, 2014, 2013, 2011

Open AccessArticle Passive Micromixers with Interlocking Semi-Circle and Omega-Shaped Modules: Experiments and Simulations
Micromachines 2015, 6(7), 953-968; doi:10.3390/mi6070953
Received: 3 June 2015 / Revised: 6 July 2015 / Accepted: 14 July 2015 / Published: 22 July 2015
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Abstract
This study presents experiments and computational simulations of single-layer passive micromixer designs. The proposed designs consist of chains of interlocking semicircles and omega-shaped mixing modules. The performance of the new designs is compared with the concentric spiral channel configuration. The micromixers are [...] Read more.
This study presents experiments and computational simulations of single-layer passive micromixer designs. The proposed designs consist of chains of interlocking semicircles and omega-shaped mixing modules. The performance of the new designs is compared with the concentric spiral channel configuration. The micromixers are intended to be integrated into a lab on chip (LOC) micro-system that operates under continuous flow conditions. The purpose behind the multi-curvature in these designs is the introduction of Dean vortices in addition to molecular diffusion in order to enhance the mixing performance. The micromixers were fabricated in PDMS (Polydimethylsiloxane) and bonded to a glass substrate. A three-dimensional computational model of micromixers was carried out using Fluent ANSYS. In experiments, the mixing of a 1 g/L fluorescein isothiocyanate diluted in distilled water was observed and photographed using a charge-coupled device (CCD) microscopic camera. The obtained images were processed to determine the mixing intensity at different Reynolds numbers. The standard deviation (σ) of the fluorescence indicates the mixing completeness, which was calculated along the width of the channel at various locations downstream from the channel inlet. The value of σ = 0.5 indicates unmixed streams and 0 is for complete mixing. It is found that the two new designs have a standard deviation of nearly 0.05. Additionally, complete mixing was observed at the channel outlet as demonstrated by the fluorescence images and the numerical results. However, the location of complete mixing at different positions depends on the Reynolds number, which varies between 0.01 and 50. Good agreement was found between the experiment and the numerical results. A correlation to predict the length scale where complete mixing can be achieved is given in terms of the radius of curvature, the mixing module, and the Reynolds number. Full article
Open AccessArticle Effect of Laser-Induced Heating on Raman Measurement within a Silicon Microfluidic Channel
Micromachines 2015, 6(7), 813-830; doi:10.3390/mi6070813
Received: 24 April 2015 / Revised: 10 June 2015 / Accepted: 19 June 2015 / Published: 29 June 2015
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Abstract
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 [...] Read more.
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. Full article
Open AccessArticle On-Chip Method to Measure Mechanical Characteristics of a Single Cell by Using Moiré Fringe
Micromachines 2015, 6(6), 660-673; doi:10.3390/mi6060660
Received: 23 April 2015 / Revised: 23 May 2015 / Accepted: 29 May 2015 / Published: 3 June 2015
Cited by 5 | PDF Full-text (8441 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We propose a method to characterize the mechanical properties of cells using a robot-integrated microfluidic chip (robochip) and microscopy. The microfluidic chip is designed to apply the specified deformations to a single detached cell using an on-chip actuator probe. The reaction force [...] Read more.
We propose a method to characterize the mechanical properties of cells using a robot-integrated microfluidic chip (robochip) and microscopy. The microfluidic chip is designed to apply the specified deformations to a single detached cell using an on-chip actuator probe. The reaction force is simultaneously measured using an on-chip force sensor composed of a hollow folded beam and probe structure. In order to measure the cellular characteristics in further detail, a sub-pixel level of resolution of probe position is required. Therefore, we utilize the phase detection of moiré fringe. Using this method, the experimental resolution of the probe position reaches 42 nm. This is approximately ten times smaller than the optical wavelength, which is the limit of sharp imaging with a microscope. Calibration of the force sensor is also important in accurately measuring cellular reaction forces. We calibrated the spring constant from the frequency response, by the proposed sensing method of the probe position. As a representative of mechanical characteristics, we measured the elastic modulus of Madin-Darby Cannie Kidney (MDCK) cells. In spite of the rigid spring constant, the resolution and sensitivity were twice that achieved in our previous study. Unique cellular characteristics can be elucidated by the improvements in sensing resolution and accuracy. Full article
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Open AccessArticle On-Chip Transportation and Measurement of Mechanical Characteristics of Oocytes in an Open Environment
Micromachines 2015, 6(5), 648-659; doi:10.3390/mi6050648
Received: 21 April 2015 / Revised: 11 May 2015 / Accepted: 19 May 2015 / Published: 22 May 2015
Cited by 3 | PDF Full-text (6944 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We propose a system that transports oocytes and measures their mechanical characteristics in an open environment using a robot integrated microfluidic chip (chip). The cells are transported through a micropillar array in the chip, and their characteristics are measured by a mechanical [...] Read more.
We propose a system that transports oocytes and measures their mechanical characteristics in an open environment using a robot integrated microfluidic chip (chip). The cells are transported through a micropillar array in the chip, and their characteristics are measured by a mechanical probe and a force sensor. Because the chip has an open microchannel, important cells such as oocytes are easily introduced and collected without the risk for losing them. In addition, any bubbles trapped in the chip, which degrade the measurement precision, are easily removed. To transport the oocytes through the open microchannel, we adopt a transportation technique based on a vibration-induced flow. Under this flow, oocytes arrive at the measurement point, where their mechanical characteristics are determined. We demonstrate the introduction, transportation, measurement of mechanical characteristics, and collection of oocytes using this system. Full article
Open AccessArticle Optimizing Polymer Lab-on-Chip Platforms for Ultrasonic Manipulation: Influence of the Substrate
Micromachines 2015, 6(5), 574-591; doi:10.3390/mi6050574
Received: 10 February 2015 / Revised: 28 April 2015 / Accepted: 29 April 2015 / Published: 7 May 2015
Cited by 1 | PDF Full-text (3332 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The choice of substrate material in a chip that combines ultrasound with microfluidics for handling biological and synthetic microparticles can have a profound effect on the performance of the device. This is due to the high surface-to-volume ratio that exists within such [...] Read more.
The choice of substrate material in a chip that combines ultrasound with microfluidics for handling biological and synthetic microparticles can have a profound effect on the performance of the device. This is due to the high surface-to-volume ratio that exists within such small structures and acquires particular relevance in polymer-based resonators with 3D standing waves. This paper presents three chips developed to perform particle flow-through separation by ultrasound based on a polymeric SU-8 layer containing channelization over three different substrates: Polymethyl methacrylate (PMMA); Pyrex; and a cracked PMMA composite-like structure. Through direct observations of polystyrene microbeads inside the channel, the three checked chips exhibit their potential as disposable continuous concentration devices with different spatial pressure patterns at frequencies of resonance close to 1 Mhz. Chips with Pyrex and cracked PMMA substrates show restrictions on the number of pressure nodes established in the channel associated with the inhibition of 3D modes in the solid structure. The glass-substrate chip presents some advantages associated with lower energy requirements to collect particles. According to the results, the use of polymer-based chips with rigid substrates can be advantageous for applications that require short treatment times (clinical tests handling human samples) and low-cost fabrication. Full article

2014

Jump to: 2016, 2015, 2013, 2011

Open AccessArticle Coplanar Electrode Layout Optimized for Increased Sensitivity for Electrical Impedance Spectroscopy
Micromachines 2015, 6(1), 110-120; doi:10.3390/mi6010110
Received: 17 November 2014 / Accepted: 24 December 2014 / Published: 30 December 2014
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Abstract
This work describes an improvement in the layout of coplanar electrodes for electrical impedance spectroscopy. We have developed, fabricated, and tested an improved electrode layout, which improves the sensitivity of an impedance flow cytometry chip. The improved chip was experimentally tested and [...] Read more.
This work describes an improvement in the layout of coplanar electrodes for electrical impedance spectroscopy. We have developed, fabricated, and tested an improved electrode layout, which improves the sensitivity of an impedance flow cytometry chip. The improved chip was experimentally tested and compared to a chip with a conventional electrode layout. The improved chip was able to discriminate 0.5 μm beads from 1 μm as opposed to the conventional chip. Furthermore, finite element modeling was used to simulate the improvements in electrical field density and uniformity between the electrodes of the new electrode layout. Good agreement was observed between the model and the obtained experimental results. Full article
Open AccessArticle Predictable Duty Cycle Modulation through Coupled Pairing of Syringes with Microfluidic Oscillators
Micromachines 2014, 5(4), 1254-1269; doi:10.3390/mi5041254
Received: 24 October 2014 / Revised: 19 November 2014 / Accepted: 19 November 2014 / Published: 27 November 2014
Cited by 2 | PDF Full-text (2622 KB) | HTML Full-text | XML Full-text
Abstract
The ability to elicit distinct duty cycles from the same self-regulating microfluidic oscillator device would greatly enhance the versatility of this micro-machine as a tool, capable of recapitulating in vitro the diverse oscillatory processes that occur within natural systems. We report a [...] Read more.
The ability to elicit distinct duty cycles from the same self-regulating microfluidic oscillator device would greatly enhance the versatility of this micro-machine as a tool, capable of recapitulating in vitro the diverse oscillatory processes that occur within natural systems. We report a novel approach to realize this using the coordinated modulation of input volumetric flow rate ratio and fluidic capacitance ratio. The demonstration uses a straightforward experimental system where fluid inflow to the oscillator is provided by two syringes (of symmetric or asymmetric cross-sectional area) mounted upon a single syringe pump applying pressure across both syringes at a constant linear velocity. This produces distinct volumetric outflow rates from each syringe that are proportional to the ratio between their cross-sectional areas. The difference in syringe cross-sectional area also leads to differences in fluidic capacitance; this underappreciated capacitive difference allows us to present a simplified expression to determine the microfluidic oscillators duty cycle as a function of cross-sectional area. Examination of multiple total volumetric inflows under asymmetric inflow rates yielded predictable and robust duty cycles ranging from 50% to 90%. A method for estimating the outflow duration for each inflow under applied flow rate ratios is provided to better facilitate the utilization of this system in experimental protocols requiring specific stimulation and rest intervals. Full article
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Open AccessArticle High Resolution Cell Positioning Based on a Flow Reduction Mechanism for Enhancing Deformability Mapping
Micromachines 2014, 5(4), 1188-1201; doi:10.3390/mi5041188
Received: 23 September 2014 / Revised: 30 October 2014 / Accepted: 11 November 2014 / Published: 18 November 2014
Cited by 4 | PDF Full-text (1505 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The dispersion of cell deformability mapping is affected not only by the resolution of the sensing system, but also by cell deformability itself. In order to extract the pure deformability characteristics of cells, it is necessary to improve the resolution of cell [...] Read more.
The dispersion of cell deformability mapping is affected not only by the resolution of the sensing system, but also by cell deformability itself. In order to extract the pure deformability characteristics of cells, it is necessary to improve the resolution of cell actuation in the sensing system, particularly in the case of active sensing, where an actuator is essential. This paper proposes a novel concept, a “flow reduction mechanism”, where a flow is generated by a macroactuator placed outside of a microfluidic chip. The flow can be drastically reduced at the cell manipulation point in a microchannel due to the elasticity embedded into the fluid circuit of the microfluidic system. The great advantage of this approach is that we can easily construct a high resolution cell manipulation system by combining a macro-scale actuator and a macro-scale position sensor, even though the resolution of the actuator is larger than the desired resolution for cell manipulation. Focusing on this characteristic, we successfully achieved the cell positioning based on a visual feedback control with a resolution of 240 nm, corresponding to one pixel of the vision system. We show that the utilization of this positioning system contributes to reducing the dispersion coming from the positioning resolution in the cell deformability mapping. Full article
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Open AccessArticle Raman-Spectroscopy Based Cell Identification on a Microhole Array Chip
Micromachines 2014, 5(2), 204-215; doi:10.3390/mi5020204
Received: 11 December 2013 / Revised: 5 April 2014 / Accepted: 8 April 2014 / Published: 22 April 2014
Cited by 8 | PDF Full-text (405 KB) | HTML Full-text | XML Full-text
Abstract
Circulating tumor cells (CTCs) from blood of cancer patients are valuable prognostic markers and enable monitoring responses to therapy. The extremely low number of CTCs makes their isolation and characterization a major technological challenge. For label-free cell identification a novel combination of [...] Read more.
Circulating tumor cells (CTCs) from blood of cancer patients are valuable prognostic markers and enable monitoring responses to therapy. The extremely low number of CTCs makes their isolation and characterization a major technological challenge. For label-free cell identification a novel combination of Raman spectroscopy with a microhole array platform is described that is expected to support high-throughput and multiplex analyses. Raman spectra were registered from regularly arranged cells on the chip with low background noise from the silicon nitride chip membrane. A classification model was trained to distinguish leukocytes from myeloblasts (OCI-AML3) and breast cancer cells (MCF-7 and BT-20). The model was validated by Raman spectra of a mixed cell population. The high spectral quality, low destructivity and high classification accuracy suggests that this approach is promising for Raman activated cell sorting. Full article
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Open AccessReview Mini and Micro Propulsion for Medical Swimmers
Micromachines 2014, 5(1), 97-113; doi:10.3390/mi5010097
Received: 8 December 2013 / Revised: 14 February 2014 / Accepted: 14 February 2014 / Published: 26 February 2014
Cited by 14 | PDF Full-text (626 KB) | HTML Full-text | XML Full-text
Abstract
Mini and micro robots, which can swim in an underwater environment, have drawn widespread research interests because of their potential applicability to the medical or biological fields, including delivery and transportation of bio-materials and drugs, bio-sensing, and bio-surgery. This paper reviews the [...] Read more.
Mini and micro robots, which can swim in an underwater environment, have drawn widespread research interests because of their potential applicability to the medical or biological fields, including delivery and transportation of bio-materials and drugs, bio-sensing, and bio-surgery. This paper reviews the recent ideas and developments of these types of self-propelling devices, ranging from the millimeter scale down to the micro and even the nano scale. Specifically, this review article makes an emphasis on various propulsion principles, including methods of utilizing smart actuators, external magnetic/electric/acoustic fields, bacteria, chemical reactions, etc. In addition, we compare the propelling speed range, directional control schemes, and advantages of the above principles. Full article
Open AccessArticle The Migration of Cancer Cells in Gradually Varying Chemical Gradients and Mechanical Constraints
Micromachines 2014, 5(1), 13-26; doi:10.3390/mi5010013
Received: 1 December 2013 / Revised: 31 December 2013 / Accepted: 10 January 2014 / Published: 22 January 2014
Cited by 1 | PDF Full-text (906 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We report a novel approach to study cell migration under physical stresses by utilizing established growth factor chemotaxis. This was achieved by studying cell migration in response to epidermal growth factor (EGF) chemoattraction in a gradually tapered space, imposing mechanical stresses. The [...] Read more.
We report a novel approach to study cell migration under physical stresses by utilizing established growth factor chemotaxis. This was achieved by studying cell migration in response to epidermal growth factor (EGF) chemoattraction in a gradually tapered space, imposing mechanical stresses. The device consisted of two 5-mm-diameter chambers connected by ten 600 µm-long and 10 µm-high tapered microchannels. The taper region gradually changes the width of the channel. The channels tapered from 20 µm to 5 µm over a transition length of 50 µm at a distance of 250 µm from one of the chambers. The chemoattractant drove cell migration into the narrow confines of the tapered channels, while the mechanical gradient clearly altered the migration of cells. Cells traversing the channels from the wider to narrow-end and vice versa were observed using time-lapsed imaging. Our results indicated that the impact of physical stress on cell migration patterns may be cell type specific. Full article

2013

Jump to: 2016, 2015, 2014, 2011

Open AccessCommunication Monodisperse Water-in-Oil-in-Water (W/O/W) Double Emulsion Droplets as Uniform Compartments for High-Throughput Analysis via Flow Cytometry
Micromachines 2013, 4(4), 402-413; doi:10.3390/mi4040402
Received: 5 September 2013 / Revised: 5 November 2013 / Accepted: 19 November 2013 / Published: 3 December 2013
Cited by 5 | PDF Full-text (1181 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Here we report the application of monodisperse double emulsion droplets, produced in a single step within partially hydrophilic/partially hydrophobic microfluidic devices, as defined containers for quantitative flow cytometric analysis. Samples with varying fluorophore concentrations were generated, and a clear correlation between dye [...] Read more.
Here we report the application of monodisperse double emulsion droplets, produced in a single step within partially hydrophilic/partially hydrophobic microfluidic devices, as defined containers for quantitative flow cytometric analysis. Samples with varying fluorophore concentrations were generated, and a clear correlation between dye concentration and fluorescence signals was observed. Full article
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Open AccessArticle Formation of Tunable, Emulsion Micro-Droplets Utilizing Flow-Focusing Channels and a Normally-Closed Micro-Valve
Micromachines 2013, 4(3), 306-320; doi:10.3390/mi4030306
Received: 13 June 2013 / Revised: 7 July 2013 / Accepted: 8 July 2013 / Published: 17 July 2013
Cited by 1 | PDF Full-text (434 KB) | HTML Full-text | XML Full-text
Abstract
A mono-dispersed emulsion is of great significance in many chemical, biomedical and industrial applications. The current study reports a new microfluidic chip capable of forming tunable micro-droplets in liquids for emulsification applications. It can precisely generate size-tunable, uniform droplets using flow-focusing channels [...] Read more.
A mono-dispersed emulsion is of great significance in many chemical, biomedical and industrial applications. The current study reports a new microfluidic chip capable of forming tunable micro-droplets in liquids for emulsification applications. It can precisely generate size-tunable, uniform droplets using flow-focusing channels and a normally-closed valve, which is opened by a pneumatic suction force. Experimental data showed that micro-droplets with a diameter ranging from several to tens of micrometers could be precisely generated with a high uniformity. The droplet size is experimentally found to be dependent on the velocity of the dispersed-phase liquid, which is controlled by the deflection of the suction membrane. Emulsions with droplet sizes ranging from 5.5 to 55 μm are successfully observed. The variation in droplet sizes is from 3.8% to 2.5%. The micro-droplets have a uniform size and droplets smaller than those reported in previous studies are possible with this approach. This new microfluidic device can be promising for emulsification and other related applications. Full article
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2011

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Open AccessArticle FISHprep: A Novel Integrated Device for Metaphase FISH Sample Preparation
Micromachines 2011, 2(2), 116-128; doi:10.3390/mi2020116
Received: 10 February 2011 / Revised: 25 March 2011 / Accepted: 27 March 2011 / Published: 4 April 2011
Cited by 5 | PDF Full-text (904 KB) | HTML Full-text | XML Full-text
Abstract
We present a novel integrated device for preparing metaphase chromosomes spread slides (FISHprep). The quality of cytogenetic analysis from patient samples greatly relies on the efficiency of sample pre-treatment and/or slide preparation. In cytogenetic slide preparation, cell cultures are routinely used to [...] Read more.
We present a novel integrated device for preparing metaphase chromosomes spread slides (FISHprep). The quality of cytogenetic analysis from patient samples greatly relies on the efficiency of sample pre-treatment and/or slide preparation. In cytogenetic slide preparation, cell cultures are routinely used to process samples (for culture, arrest and fixation of cells) and/or to expand limited amount of samples (in case of prenatal diagnostics). Arguably, this expansion and other sample pretreatments form the longest part of the entire diagnostic protocols spanning over 3–4 days. We present here a novel device with an integrated expansion chamber to culture, arrest and fix metaphase cells followed by a subsequent splashing protocol leading to ample metaphase chromosome spreads on a glass slide for metaphase FISH analysis. The device provides an easy, disposable, low cost, integrated solution with minimal handling for metaphase FISH slide preparation. Full article
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