scholarly journals Cell Motion in a Two-Stream Microfluidic Channel

2009 ◽  
Vol 3 (2) ◽  
Author(s):  
J. Hanna ◽  
T. B. Darr ◽  
A. Hubel ◽  
C. Mata ◽  
E. K. Longmire ◽  
...  

Microfluidic channels have been proposed as a method for removal of cryoprotective agents from cell suspensions [Fleming, Longmire, and Hubel, J. Biomech. Eng. 129, 703 (2007)]. The device tested consists of a rectangular cross section channel of 500 μm depth, 25 mm width, and 160 mm length, through which a cell suspension and wash stream flow in parallel. Cryoprotective agents diffuse from the cell stream to the wash stream and the wash stream is discarded. The washed cell stream is then ready for use. This device must be capable of removing 95% of the dimethyl sulfoxide (DMSO) from the cell stream with minimal cell losses. Our previous studies have demonstrated our ability to remove DMSO [Mata, Longmire, McKenna, Glass, and Hubel, Microfluid. Nanofluid. 5, 529 (2008)]. The next phase of the investigation involves characterizing the influence of flow conditions on cell motion through the device. To that end, Jurkat cells (lymphoblasts) in a 10% DMSO solution were flowed through the microfluidic channel in parallel with a wash stream composed of phosphate buffered saline solution (PBS). Average cell stream velocities were varied from 0.94 to 8.5 mm/s (Re 1.7 to 6.0). Cell viability at the outlet was high, indicating that cells are not damaged during their passage through the device. Gravitational settling caused an accumulation of cells near the bottom of the channel, where flow velocities are low. Cell settling leads results in an initial transient period for cell motion through the device. For the initial portion of cells flowing through the device, cells tend to accumulate in the device until a critical device population time is reached. Cell recovery (number of cells out of the device divided by the number of cells input to the device) is high (90–100%) after the device has been fully populated. For a single stage device with average cell stream velocities of ⩾6 mm/s, cell recovery was 90–100%. As more stages are added to the device, the population time for the device increases. Gravitational settling of cells also leads to a time-varying cell concentration from the input syringe to the inlet of the channel, as well as cell losses due to cells remaining in the horizontally-oriented syringe. Reorienting the syringes to a vertical position eliminates these losses. Cell motion within the channel can be modulated by the flow conditions used. For sufficiently high Reynolds numbers, the Segre-Silberberg effect [Segre and Silberberg, J. Fluid Mech. 14, 115 (1962)] can be used to move cells from the low velocity region of the cell stream to a higher velocity region thereby reducing the transient portion of processing the cells and improving overall recovery of cells through the device.

Biosensors ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 65
Author(s):  
Puneet Manocha ◽  
Gitanjali Chandwani

Molecular communication is a bioinspired communication that enables macro-scale, micro-scale and nano-scale devices to communicate with each other. The molecular communication system is prone to severe signal attenuation, dispersion and delay, which leads to performance degradation as the distance between two communicating devices increases. To mitigate these challenges, relays are used to establish reliable communication in microfluidic channels. Relay assisted molecular communication systems can also enable interconnection among various entities of the lab-on-chip for sharing information. Various relaying schemes have been proposed for reliable molecular communication systems, most of which lack practical feasibility. Thus, it is essential to design and develop relays that can be practically incorporated into the microfluidic channel. This paper presents a novel design of passive in-line relay for molecular communication system that can be easily embedded in the microfluidic channel and operate without external energy. Results show that geometric modification in the microfluidic channel can act as a relay and restore the degraded signal up-to 28%.


2017 ◽  
Vol 2017 (1) ◽  
pp. 000569-000575 ◽  
Author(s):  
André Cardoso ◽  
Raquel Pinto ◽  
Elisabete Fernandes ◽  
Steffen Kroehnert

Abstract Due to its versatility for high density, heterogeneous integration, Wafer Level Fan Out (WLFO) packaging has recently seen a tremendous growth in a broad array of applications, from telecommunications and automotive, to optical and environmental sensing, while addressing the challenges of the next big wave of the Internet of Things (IoT). In this context, WLFO is continuously being challenged to include new families of MEMS/NEMS/MOEMS sensors, low thermal budget devices and biochips with microfluidics for biomedical applications. Recent developments in WLFO technology by NANIUM [1] demonstrated the implementation of a keep-out-zone (KOZ) mechanism intended to 1st) protect sensitive sensor areas during the backend processing of WLFO wafers and 2nd) create open zones on the Re-Distribution Layers (RDL). This way, the KOZ mechanism provides a physical, direct path from the embedded device to the environment. This is a necessary feature for environment sensing (e.g., pressure) or to create optical paths free of dielectric and protected from the harsh chemistry steps of the WLFO process. This paper describes new developments on KOZ, implemented with SU-8 photoresist as a WLFO dielectric, whose application is a novelty in the WLFO platform. The use of SU-8 and the KOZ with it, addresses some gaps of the current WLFO technology towards the integration of chips with bio-sensitive areas and sensors with low thermal budget. Due to its well-known bio-compatibility and inert behavior, SU-8 can be used as a neutral dielectric to be in direct contact to target fluids (e.g., sera, blood). Also, due to its low curing temperature, SU-8 allows a very low temperature WLFO process and thus the embedding of temperature-limited devices that have been outside the WLFO realm, for example, magneto-resistive or magnetic-spin sensor chips, which degrades its performance above 160°C. More interestingly, SU-8 exhibits a particular non-conformal behavior, which creates very smooth surfaces even over the mildly rough mold compound area of a fan-out package. Adding to this, SU-8 is readily available in the market in a wide range of thicknesses, spanning from 0.5 μm to >100 μm, and further allowing multiple spin coatings to build thick layers. Thus, SU-8 can provide smooth and deep enough channels for microfluidic flow over the chip sensing areas and, at the same time, provide the necessary layer thickness discrimination for the KOZ mechanism. Combining these features, the SU-8 layers in WLFO can play the triple role of 1) RDL dielectric insulation, 2) KOZ mechanism and 3) embedded microfluidic channels as part of the RDL. In summary, besides the unprecedented use of SU-8 in WLFO packaging, KOZ implementation on SU-8 provides a true, attainable bridge between WLFO and integrated microfluidic applications, for biosensing and biomedical applications in general. Outlooking the potentialities of such a merge, a Fan-Out package can embed several chips interconnected by RDL lines, as it currently allows, and also connected by microfluidic channel for multi-point, multi-function biosensing, constituting a true Lab-on-Package, cost-effective solution. Instead of building all sensing areas and microfluidic channels over a large silicon (Si) chip, this solution builds the feed-in, feed-out areas of the microfluidic channel over the inexpensive fan-out area, minimizing the sensing chip area, with the consequent front-end cost reduction.


Author(s):  
Toshifumi Ohkubo ◽  
Nobuyuki Terada ◽  
Yoshikazu Yoshida

A resin-based optical total analysis system (O-TAS) which consists both of microfluidic channels and light waveguides [1] is thought to be one of the most promising components in developing a “ubiquitous human healthcare system” in the near future. Along with this technology trend, we have already developed a transparent epoxy-resin-based optical TAS chip which has a specially prepared light waveguide structure of radially arranged configuration at an intersection portion with a microfluidic channel, in order to detect directivity of fluorescence from fluorescent substance attached micro particles [2],[3]. Schematic diagram of the optical TAS is shown in Figure 1. In the latest research, utilizing an AC modulated laser source and time-series averaging function on detected signal waveforms, we could have successfully obtained directivities of fluorescence from 5-μm-diameter particles with higher signal to noise (S/N) ratio [3].


Proceedings ◽  
2018 ◽  
Vol 2 (13) ◽  
pp. 870
Author(s):  
Kerem Kaya ◽  
Ahmet Yasin Celik ◽  
Senol Mutlu

This work reports for the first-time integration of continuous microfluidic channels to the paper-based electro-osmotic pumps (EOPs) with liquid bridges. In addition, 0.2 μm pore sized cellulose acetate (CA) membrane filter is used to eliminate pressure-driven flow instead of filter paper which is common in paper microfluidics and has an average pore size of 10 μm. A factor of 57 increase in hydraulic resistance is achieved with the new paper. Fabrication of the pumps and microfluidic channels using paper, wax, adhesive film and PMMA plates is explained. Volumetric flow rate of 19 nL/min is achieved in the microfluidic system with 61 V/cm electrical field magnitude applied to DI water. The capability of the integrated system is shown with precise liquid motion in a Y-shaped microfluidic channel integrated with two EOPs.


Author(s):  
Michael B. Lawrence ◽  
Brian J. Schmidt

Recruitment rate measurements of micro-scale particles, such as cells or microbeads, to biofunctional surfaces is difficult because factors such as uneven ligand distributions, particle collisions, variable particle fluxes, and molecular-scale surface separation distances that combine to obfuscate the ability to link the observed particle behavior with the governing nanoscale biophysics. We report the development of a hydrodynamically-conditioned micropattern catch strip assay to measure microparticle and cellular recruitment kinetics. The assay exploited patterning within microfluidic channels and the mechanostability of selectin bonds to create reaction geometries that confined a microbead flux to within 200 nm of the surface under flow conditions. Systematic control of capillary action enabled the creation of homogenous or gradient ligand distributions. The method enabled the measurement of particle recruitment rates (keff, s−1) that were primarily determined by the interaction of the biomolecular pair being investigated. The method may be well suited for analysis of reaction rates between surface-bound molecules in the presence of convective flow patterns.


2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Sungil Kim ◽  
Jeongtae Kim ◽  
Yeun-Ho Joung ◽  
Sanghoon Ahn ◽  
Jiyeon Choi ◽  
...  

Abstract We present the selective laser-induced etching (SLE) process and design guidelines for the fabrication of three-dimensional (3D) microfluidic channels in a glass. The SLE process consisting of laser direct patterning and wet chemical etching uses different etch rates between the laser modified area and the unmodified area. The etch selectivity is an important factor for the processing speed and the fabrication resolution of the 3D structures. In order to obtain the maximum etching selectivity, we investigated the process window of the SLE process: the laser pulse energy, pulse repetition rate, and scan speed. When using potassium hydroxide (KOH) as a wet etchant, the maximum etch rate of the laser-modified glass was obtained to be 166 μm/h, exhibiting the highest selectivity about 333 respect to the pristine glass. Based on the optimized process window, a 3D microfluidic channel branching to three multilayered channels was successfully fabricated in a 4 mm-thick glass. In addition, appropriate design guidelines for preventing cracks in a glass and calibrating the position of the dimension of the hollow channels were studied.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mark MacKenzie ◽  
Haonan Chi ◽  
Manoj Varma ◽  
Parama Pal ◽  
Ajoy Kar ◽  
...  

AbstractWe report on an optimized fabrication protocol for obtaining silver nanoparticles on fused silica substrates via laser photoreduction of a silver salt solution. We find that multiple scans of the laser over the surface leads to a more uniform coverage of densely packed silver nanoparticles of approximately 50 nm diameter on the fused silica surface. Our substrates yield Raman enhancement factors of the order of 1011 of the signal detected from crystal violet. We use a theoretical model based on scanning electron microscope (SEM) images of our substrates to explain our experimental results. We also demonstrate how our technique can be extended to embedding silver nanoparticles in buried microfluidic channels in glass. The in situ laser inscription of silver nanoparticles on a laser machined, sub-surface, microfluidic channel wall within bulk glass paves the way for developing 3D, monolithic, fused silica surface enhance Raman spectroscopy (SERS) microfluidic sensing devices.


Author(s):  
Hsiu-hung Chen ◽  
Dayong Gao

The manipulation of particles and cells in micro-fluids, such as cell suspensions, is a fundamental task in Lab-on-a-Chip applications. According to their analysis purposes in either the pre- or post-processing stage, particles/cells flowing inside a microfluidic channel are handled by means of enriching, trapping, separating or sorting. In this study, we report the use of patterning flows produced by a series of grooved surfaces with different geometrical setups integrated into a microfluidic device, to continuously manipulate the flowing particles (5 to 20 μm in diameters) of comparable sizes to the depth of the channel in ways of: 1) concentrating, 2) focusing, and 3) potential separating. The device is fabricated using soft lithographic techniques and is composed of inlets, microfluidic channels, and outlets for loading, manipulating and retrieving cell suspensions, respectively. Such fabrication methods allow rapid prototyping of micron or submicron structures with multiple layers and replica molding on those fabricated features in a clear polymer. The particles are evenly distributed in the entrance of the microchannel and illustrate the enriching, focusing, or size-selective profiles after passing through the patterning grooves. We expect that the techniques of manipulating cell suspensions from this study can facilitate the development of cell-based devices on 1) the visualization of counting, 2) the visualization of sizing, and 3) the particle separating.


Author(s):  
Hing Wah Lee ◽  
Parthiban Arunasalam ◽  
Ishak A. Azid ◽  
Kankanhally N. Seetharamu

In this study, a hybridized neural-genetic optimization methodology realized by embedding finite element analysis (FEA) trained artificial neural networks (ANN) into genetic algorithms (GA) is used to optimize temperature control in a ceramic based continuous flow polymerase chain reaction (CPCR) device. The CPCR device requires three thermally isolated zones of 94°C, 65°C and 72°C for the corresponding process of denaturing, annealing and extension to complete a cycle of polymerase chain reaction. Three separately addressable heaters provide heat input to each zone, microfluidic channels allow for the transport of fluid between zones and thermal isolation between the zones is maintained by machining air-gaps into the device. The most important aspect of temperature control in the CPCR is to maintain temperature distribution at each reaction zone with a precision of ±1°C or better irrespective of changing ambient conditions. Results obtained from the FEA simulation are compared with published experimental work. Simulation results show good comparison with experimental work for the temperature control in each reaction zone of the microfluidic channels. The data is then used to train the ANN to predict the temperature distribution of the microfluidic channel for new heater input power and fluid flow rate. Using these data, optimization of temperature control in the CPCR device is achieved by embedding the trained ANN results as a fitness function into GA. The objective of the optimization is to minimize the temperature difference in each reaction zone of the microfluidic channel while satisfying the residence time requirement. Finally, the optimized results for the CPCR device are used to build a new FEA model for numerical simulation analysis. The simulation results for the neural-genetic optimized CPCR model and the initial CPCR model are then compared. The neural-genetic optimized model shows a significant improvement from the initial model establishing the optimization methods superiority.


Author(s):  
Hsiu-hung Chen ◽  
Dayong Gao

The manipulation of particles in fluids using microfluidic devices is a fundamental task in Lab-on-a-Chip applications. Grooved structures have been widely studied in particle handling and fluid mixing in microfluidic channel systems. In this study, we report use of patterning flows produced by a series of grooved surfaces with different geometrical setups integrated into a microfluidic device, to continuously manipulate the flowing particles, ranging from 6 to 20 μm in diameters, of comparable sizes to the depth of the channel. COMSOL, a multiphysics modeling software that can help predict engineering trends, is used to systematically quantify the following parameters: 1) channel depth, 2) groove width, 3) groove depth, 4) groove angle, and 5) flow speed, which may affect the performance of separation for flowing particles inside the channel. The device is fabricated using softlithographic techniques and is composed of inlets, microfluidic channels, and outlets for loading, manipulating and retrieving cell suspensions, respectively. Experimental results indicated that the particles were evenly distributed in the entrance of the microchannel and illustrate patterns of enriching, focusing, or size-selective profiles after passing through the grooved area. The preliminary simulation results also demonstrated that particles tend to bias towards the sidewall after flowing through the grooves.


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