scholarly journals High Throughput Viscoelastic Particle Focusing and Separation in Spiral Microchannels

2021 ◽  
Author(s):  
Tharagan Kumar ◽  
Harisha Ramachandraiah ◽  
Sharath Narayana Iyengar ◽  
Indradumna Banerjee ◽  
Gustaf Mårtensson ◽  
...  
Keyword(s):  
High Resolution ◽  
High Throughput ◽  
Separation Efficiency ◽  
Point Of Care ◽  
Outer Wall ◽  
Reynolds Numbers ◽  
Inertial Microfluidics ◽  
Flow Rates ◽  
Particle Focusing ◽  
Sample Flow Rate

Abstract Passive particle manipulation using inertial and elasto-inertial microfluidics have received substantial interest in recent years and have found various applications in high throughput particle sorting and separation. For separation applications, elasto-inertial microfluidics has thus far been applied at substantial lower flow rates as compared to inertial microfluidics. In this work, we explore viscoelastic particle focusing and separation in spiral channels at two orders of magnitude higher Reynolds numbers than previously reported. We show that the balance between dominant inertial lift force, dean drag force and elastic force enables stable 3D particle focusing at dynamically high Reynolds numbers. Using a two-turn spiral, we show that particles, initially pinched towards the inner wall using an elasticity enhancer, PEO (polyethylene oxide), as sheath migrate towards the outer wall strictly based on size and can be effectively separated with high precision. As a proof of principle for high resolution particle separation, 15 µm particles were effectively separated from 10 µm particles. A separation efficiency of 98% for the 10 µm and 97% for the 15µm particles was achieved. Furthermore, we demonstrate sheath-less, high throughput, separation using a novel integrated two-spiral device and achieved a separation efficiency of 89% for the 10 µm and 99% for the 15µm particles at a sample flow rate of 1 mL/ml – a throughput previously only reported for inertial microfluidics. We anticipate the ability to precisely control particles in 3D at extremely high flow rates will open up several applications, including the development of ultra-high throughput microflow cytometers and high-resolution separation of rare cells for point of care diagnostics.

scholarly journals High throughput viscoelastic particle focusing and separation in spiral microchannels

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tharagan Kumar ◽  
Harisha Ramachandraiah ◽  
Sharath Narayana Iyengar ◽  
Indradumna Banerjee ◽  
Gustaf Mårtensson ◽  
...  
Keyword(s):  
High Resolution ◽  
High Throughput ◽  
Separation Efficiency ◽  
Point Of Care ◽  
Outer Wall ◽  
Reynolds Numbers ◽  
Inertial Microfluidics ◽  
Flow Rates ◽  
Particle Focusing ◽  
Sample Flow Rate

AbstractPassive particle manipulation using inertial and elasto-inertial microfluidics have received substantial interest in recent years and have found various applications in high throughput particle sorting and separation. For separation applications, elasto-inertial microfluidics has thus far been applied at substantial lower flow rates as compared to inertial microfluidics. In this work, we explore viscoelastic particle focusing and separation in spiral channels at two orders of magnitude higher Reynolds numbers than previously reported. We show that the balance between dominant inertial lift force, dean drag force and elastic force enables stable 3D particle focusing at dynamically high Reynolds numbers. Using a two-turn spiral, we show that particles, initially pinched towards the inner wall using an elasticity enhancer, PEO (polyethylene oxide), as sheath migrate towards the outer wall strictly based on size and can be effectively separated with high precision. As a proof of principle for high resolution particle separation, 15 µm particles were effectively separated from 10 µm particles. A separation efficiency of 98% for the 10 µm and 97% for the 15 µm particles was achieved. Furthermore, we demonstrate sheath-less, high throughput, separation using a novel integrated two-spiral device and achieved a separation efficiency of 89% for the 10 µm and 99% for the 15 µm particles at a sample flow rate of 1 mL/min—a throughput previously only reported for inertial microfluidics. We anticipate the ability to precisely control particles in 3D at extremely high flow rates will open up several applications, including the development of ultra-high throughput microflow cytometers and high-resolution separation of rare cells for point of care diagnostics.

scholarly journals High resolution and high throughput bacteria separation from blood using elasto-inertial microfluidics

2020 ◽  
Author(s):  
Sharath Narayana Iyengar ◽  
Tharagan Kumar ◽  
Gustaf Mårtensson ◽  
Aman Russom
Keyword(s):  
Sample Preparation ◽  
Blood Sample ◽  
High Throughput ◽  
Blood Cells ◽  
Separation Efficiency ◽  
Unmet Need ◽  
Outer Wall ◽  
Separation Performance ◽  
Label Free ◽  
Inertial Microfluidics

AbstractImproved sample preparation has the potential to address a huge unmet need for fast turnaround sepsis tests that enable early administration of appropriate antimicrobial therapy. In recent years, inertial and elasto-inertial microfluidics-based sample preparation has gained substantial interest for bioparticle separation applications. However, for applications in blood stream infections the throughput and bacteria separation efficiency has thus far been limited. In this work, for the first time we report elasto-inertial microfluidics-based bacteria isolation from blood at throughputs and efficiencies unparalleled with current microfluidics-based state of the art. In the method, bacteria-spiked blood sample is prepositioned close to the outer wall of a spiral microchannel using a viscoelastic sheath buffer. The blood cells will remain fully focused throughout the length of the channel while bacteria migrate to the inner wall for effective separation. Initially, particles of different sizes were used to investigate particle focusing and the separation performance of the spiral device. A separation efficiency of 96% for the 1 µm particles was achieved, while 100% of 3 µm particles were recovered at the desired outlet at a high throughput of 1 mL/min. Following, processing blood samples revealed a minimum of 1:2 dilution was necessary to keep the blood cells fully focus at the outer wall. In experiments involving bacteria spiked in diluted blood, viable E.coli were continuously separated at a total flow rate of 1 mL/min, with an efficiency between 82 to 90% depending on the blood dilution. Using a single spiral, it takes 40 minutes to process 1 mL of blood at a separation efficiency of 82% and 3 hours at 90% efficiency. To the best of our knowledge, this is the highest blood sample throughput per single microfluidic chip reported for the corresponding separation efficiency. As such, the label-free, passive and high throughput bacteria isolation method has a great potential for speeding up downstream phenotypic and molecular analysis of bacteria.

scholarly journals High-Throughput Particle Concentration Using Complex Cross-Section Microchannels

Micromachines ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 440 ◽  
Author(s):  
Asma Mihandoust ◽  
Sajad Razavi Bazaz ◽  
Nahid Maleki-Jirsaraei ◽  
Majid Alizadeh ◽  
Robert A. Taylor ◽  
...  
Keyword(s):  
Cross Section ◽  
High Throughput ◽  
Cross Sections ◽  
Particle Concentration ◽  
Separation Efficiency ◽  
Channel Cross Section ◽  
Total Width ◽  
Particle Focusing ◽  
Complex Cross ◽  
Complex Cross Section

High throughput particle/cell concentration is crucial for a wide variety of biomedical, clinical, and environmental applications. In this work, we have proposed a passive spiral microfluidic concentrator with a complex cross-sectional shape, i.e., a combination of rectangle and trapezoid, for high separation efficiency and a confinement ratio less than 0.07. Particle focusing in our microfluidic system was observed in a single, tight focusing line, in which higher particle concentration is possible, as compared with simple rectangular or trapezoidal cross-sections with similar flow area. The sharper focusing stems from the confinement of Dean vortices in the trapezoidal region of the complex cross-section. To quantify this effect, we introduce a new parameter, complex focusing number or CFN, which is indicative of the enhancement of inertial focusing of particles in these channels. Three spiral microchannels with various widths of 400 µm, 500 µm, and 600 µm, with the corresponding CFNs of 4.3, 4.5, and 6, respectively, were used. The device with the total width of 600 µm was shown to have a separation efficiency of ~98%, and by recirculating, the output concentration of the sample was 500 times higher than the initial input. Finally, the investigation of results showed that the magnitude of CFN relies entirely on the microchannel geometry, and it is independent of the overall width of the channel cross-section. We envision that this concept of particle focusing through complex cross-sections will prove useful in paving the way towards more efficient inertial microfluidic devices.

scholarly journals High resolution bacterial separation from blood using elasto-inertial microfluidics

2021 ◽  
Author(s):  
Sharath Narayana Iyengar ◽  
Tharagan Kumar ◽  
Gustaf Måertensson ◽  
Aman Russom
Keyword(s):  
Sample Preparation ◽  
Blood Sample ◽  
Blood Cells ◽  
High Efficiency ◽  
Separation Efficiency ◽  
Unmet Need ◽  
Outer Wall ◽  
Separation Performance ◽  
Label Free ◽  
Inertial Microfluidics

Improved sample preparation has the potential to address a huge unmet need for fast turnaround sepsis tests that enable early administration of appropriate antimicrobial therapy. In recent years, inertial and elasto-inertial microfluidics-based sample preparation has gained substantial interest for bioparticle separation applications. However, for applications in blood stream infections the throughput and bacteria separation efficiency has thus far been limited. In this work, for the first time we report elasto-inertial microfluidics-based bacteria isolation from blood at throughputs and efficiencies unparalleled with current microfluidics-based state of the art. In the method, bacteria-spiked blood sample is prepositioned close to the outer wall of a spiral microchannel using a viscoelastic sheath buffer. The blood cells will remain fully focused throughout the length of the spiral channel while bacteria migrate to the inner wall for effective separation. Initially, microparticles were used to investigate particle focusing and the separation performance of the spiral device. A separation efficiency of 96% for the 1 µm particles was achieved, while 100% of 3 µm particles were recovered at the desired outlet at a throughput (sample + sheath) of 1 mL/min. Following, processing blood samples revealed a minimum of 1:2 dilution was necessary to keep the blood cells fully focus at the outer wall. In experiments involving bacteria spiked in diluted blood, viable E.coli were continuously separated at a total flow rate of 1 mL/min, with a separation efficiency between 82 to 90% depending on the blood dilution. Using a single spiral, it takes 40 minutes to process 1 mL of whole blood at a separation efficiency of 82% and 3 hr at 90% efficiency. To the best of our knowledge, this is the highest bacteria separation efficiency from blood sample reported using inertial and elasto-inertial methods. As such, the label-free, passive high efficiency and high throughput of bacteria isolation method has a great potential for speeding up downstream phenotypic and molecular analysis of bacteria.

Cross Section Analysis of Cu Filled TSVs Based on High Throughput Plasma-FIB Milling

2012 ◽  
Author(s):  
Frank Altmann ◽  
Jens Beyersdorfer ◽  
Jan Schischka ◽  
Michael Krause ◽  
German Franz ◽  
...  
Keyword(s):  
High Resolution ◽  
Cross Section ◽  
High Throughput ◽  
Cross Sections ◽  
Electron Backscatter Diffraction ◽  
Grain Structure ◽  
Electron Backscatter ◽  
Section Surface ◽  
Backscatter Diffraction ◽  
Section Analysis

Abstract In this paper the new Vion™ Plasma-FIB system, developed by FEI, is evaluated for cross sectioning of Cu filled Through Silicon Via (TSV) interconnects. The aim of the study presented in this paper is to evaluate and optimise different Plasma-FIB (P-FIB) milling strategies in terms of performance and cross section surface quality. The sufficient preservation of microstructures within cross sections is crucial for subsequent Electron Backscatter Diffraction (EBSD) grain structure analyses and a high resolution interface characterisation by TEM.

scholarly journals Micromechanical Punching: A Versatile Method for Non-Spherical Microparticle Fabrication

Polymers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 83
Author(s):  
Ritika Singh Petersen ◽  
Anja Boisen ◽  
Stephan Sylvest Keller
Keyword(s):  
Drug Delivery ◽  
High Resolution ◽  
Physicochemical Properties ◽  
High Throughput ◽  
Liquid State ◽  
Soft Lithography ◽  
Glycolic Acid ◽  
Thermosetting Polymers ◽  
Spherical Microparticle ◽  
Spherical Microparticles

Microparticles are ubiquitous in applications ranging from electronics and drug delivery to cosmetics and food. Conventionally, non-spherical microparticles in various materials with specific shapes, sizes, and physicochemical properties have been fabricated using cleanroom-free lithography techniques such as soft lithography and its high-resolution version particle replication in non-wetting template (PRINT). These methods process the particle material in its liquid/semi-liquid state by deformable molds, limiting the materials from which the particles and the molds can be fabricated. In this study, the microparticle material is exploited as a sheet placed on a deformable substrate, punched by a robust mold. Drawing inspiration from the macro-manufacturing technique of punching metallic sheets, Micromechanical Punching (MMP) is a high-throughput technique for fabrication of non-spherical microparticles. MMP allows production of microparticles from prepatterned, porous, and fibrous films, constituting thermoplastics and thermosetting polymers. As an illustration of application of MMP in drug delivery, flat, microdisk-shaped Furosemide embedded poly(lactic-co-glycolic acid) microparticles are fabricated and Furosemide release is observed. Thus, it is shown in the paper that Micromechanical punching has potential to make micro/nanofabrication more accessible to the research and industrial communities active in applications that require engineered particles.

scholarly journals Analogue tuning of particle focusing in elasto-inertial flow

Meccanica ◽  
2021 ◽  
Author(s):  
I. Banerjee ◽  
M. E. Rosti ◽  
T. Kumar ◽  
L. Brandt ◽  
A. Russom
Keyword(s):  
Numerical Simulations ◽  
Cross Section ◽  
Immersed Boundary Method ◽  
Circular Cross Section ◽  
Finite Size ◽  
Reynolds Numbers ◽  
Immersed Boundary ◽  
Particle Focusing ◽  
Inertial Flow ◽  
Particle Behaviour

AbstractWe report a unique tuneable analogue trend in particle focusing in the laminar and weak viscoelastic regime of elasto-inertial flows. We observe experimentally that particles in circular cross-section microchannels can be tuned to any focusing bandwidths that lie between the “Segre-Silberberg annulus” and the centre of a circular microcapillary. We use direct numerical simulations to investigate this phenomenon and to understand how minute amounts of elasticity affect the focussing of particles at increasing flow rates. An Immersed Boundary Method is used to account for the presence of the particles and a FENE-P model is used to simulate the presence of polymers in a Non-Newtonian fluid. The numerical simulations study the dynamics and stability of finite size particles and are further used to analyse the particle behaviour at Reynolds numbers higher than what is allowed by the experimental setup. In particular, we are able to report the entire migration trajectories of the particles as they reach their final focussing positions and extend our predictions to other geometries such as the square cross section. We believe complex effects originate due to a combination of inertia and elasticity in the weakly viscoelastic regime, where neither inertia nor elasticity are able to mask each other’s effect completely, leading to a number of intermediate focusing positions. The present study provides a fundamental new understanding of particle focusing in weakly elastic and strongly inertial flows, whose findings can be exploited for potentially multiple microfluidics-based biological sorting applications.

scholarly journals INSIGHT: A population-scale COVID-19 testing strategy combining point-of-care diagnosis with centralized high-throughput sequencing

2021 ◽  
Vol 7 (7) ◽  
pp. eabe5054
Author(s):  
Qianxin Wu ◽  
Chenqu Suo ◽  
Tom Brown ◽  
Tengyao Wang ◽  
Sarah A. Teichmann ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Sequencing ◽  
Limit Of Detection ◽  
Point Of Care ◽  
Population Level ◽  
Reaction Products ◽  
Testing Strategy ◽  
Asymptomatic Patients ◽  
Testing Stage ◽  
Population Scale

We present INSIGHT [isothermal NASBA (nucleic acid sequence–based amplification) sequencing–based high-throughput test], a two-stage coronavirus disease 2019 testing strategy, using a barcoded isothermal NASBA reaction. It combines point-of-care diagnosis with next-generation sequencing, aiming to achieve population-scale testing. Stage 1 allows a quick decentralized readout for early isolation of presymptomatic or asymptomatic patients. It gives results within 1 to 2 hours, using either fluorescence detection or a lateral flow readout, while simultaneously incorporating sample-specific barcodes. The same reaction products from potentially hundreds of thousands of samples can then be pooled and used in a highly multiplexed sequencing–based assay in stage 2. This second stage confirms the near-patient testing results and facilitates centralized data collection. The 95% limit of detection is <50 copies of viral RNA per reaction. INSIGHT is suitable for further development into a rapid home-based, point-of-care assay and is potentially scalable to the population level.

A numerical study on combined baffles quick-separation device

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Ehsan Dehdarinejad ◽  
Morteza Bayareh ◽  
Mahmud Ashrafizaadeh
Keyword(s):  
Turbulent Flows ◽  
Separation Efficiency ◽  
Numerical Study ◽  
Turbulence Models ◽  
Complete Separation ◽  
Solid Particles ◽  
Flow Rates ◽  
Separation Device ◽  
Coupling Technique ◽  
Laminar And Turbulent Flows

Abstract The transfer of particles in laminar and turbulent flows has many applications in combustion systems, biological, environmental, nanotechnology. In the present study, a Combined Baffles Quick-Separation Device (CBQSD) is simulated numerically using the Eulerian-Lagrangian method and different turbulence models of RNG k-ε, k-ω, and RSM for 1–140 μm particles. A two-way coupling technique is employed to solve the particles’ flow. The effect of inlet flow velocity, the diameter of the splitter plane, and solid particles’ flow rate on the separation efficiency of the device is examined. The results demonstrate that the RSM turbulence model provides more appropriate results compared to RNG k-ε and k-ω models. Four thousand two hundred particles with the size distribution of 1–140 µm enter the device and 3820 particles are trapped and 380 particles leave the device. The efficiency for particles with a diameter greater than 28 µm is 100%. The complete separation of 22–28 μm particles occurs for flow rates of 10–23.5 g/s, respectively. The results reveal that the separation efficiency increases by increasing the inlet velocity, the device diameter, and the diameter of the particles.

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