Microspinning: Local Surface Mixing via Rotation of Magnetic Microparticles for Efficient Small-Volume Bioassays

The need for high-throughput screening has led to the miniaturization of the reaction volume of the chamber in bioassays. As the reactor gets smaller, surface tension dominates the gravitational or inertial force, and mixing efficiency decreases in small-scale reactions. Because passive mixing by simple diffusion in tens of microliter-scale volumes takes a long time, active mixing is needed. Here, we report an efficient micromixing method using magnetically rotating microparticles with patterned magnetization induced by magnetic nanoparticle chains. Because the microparticles have magnetization patterning due to fabrication with magnetic nanoparticle chains, the microparticles can rotate along the external rotating magnetic field, causing micromixing. We validated the reaction efficiency by comparing this micromixing method with other mixing methods such as simple diffusion and the use of a rocking shaker at various working volumes. This method has the potential to be widely utilized in suspension assay technology as an efficient mixing strategy.

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Microfluidic Magnetic Mixing at Low Reynolds Numbers and in Stagnant Fluids

Micromachines ◽

10.3390/mi10110731 ◽

2019 ◽

Vol 10 (11) ◽

pp. 731 ◽

Cited By ~ 8

Author(s):

Eriola-Sophia Shanko ◽

Yoeri van de Burgt ◽

Patrick D. Anderson ◽

Jaap M. J. den Toonder

Keyword(s):

Magnetic Beads ◽

External Source ◽

Magnetic Bead ◽

Mixing Efficiency ◽

Microfluidic Mixing ◽

Low Reynolds Number Flows ◽

Passive Mixing ◽

Magnetic Mixing ◽

Low Reynolds ◽

Active Mixing

Microfluidic mixing becomes a necessity when thorough sample homogenization is required in small volumes of fluid, such as in lab-on-a-chip devices. For example, efficient mixing is extraordinarily challenging in capillary-filling microfluidic devices and in microchambers with stagnant fluids. To address this issue, specifically designed geometrical features can enhance the effect of diffusion and provide efficient mixing by inducing chaotic fluid flow. This scheme is known as “passive” mixing. In addition, when rapid and global mixing is essential, “active” mixing can be applied by exploiting an external source. In particular, magnetic mixing (where a magnetic field acts to stimulate mixing) shows great potential for high mixing efficiency. This method generally involves magnetic beads and external (or integrated) magnets for the creation of chaotic motion in the device. However, there is still plenty of room for exploiting the potential of magnetic beads for mixing applications. Therefore, this review article focuses on the advantages of magnetic bead mixing along with recommendations on improving mixing in low Reynolds number flows (Re ≤ 1) and in stagnant fluids.

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Autonomous Internal Reflux of Magnetic Nanoparticle Chains in a Flow Channel for Efficient Detection of Waterborne Bacteria

Analytical Chemistry ◽

10.1021/acs.analchem.1c01469 ◽

2021 ◽

Author(s):

Hyeonjeong Lee ◽

Hyunsoo Han ◽

Sangmin Jeon

Keyword(s):

Magnetic Nanoparticle ◽

Flow Channel ◽

Efficient Detection ◽

Nanoparticle Chains

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High Mixing Efficiency by Modulating Inlet Frequency of Viscoelastic Fluid in Simplified Pore Structure

Processes ◽

10.3390/pr6110210 ◽

2018 ◽

Vol 6 (11) ◽

pp. 210 ◽

Cited By ~ 3

Author(s):

Meng Zhang ◽

Yunfeng Cui ◽

Weihua Cai ◽

Zhengwei Wu ◽

Yongyao Li ◽

...

Keyword(s):

Viscoelastic Fluid ◽

Essential Role ◽

Fluid Flows ◽

Fluid Mixing ◽

Modulation Method ◽

Mixing Efficiency ◽

Microscale Flow ◽

Pressure Modulation ◽

Active Mixing ◽

Junction Structure

Fluid mixing plays an essential role in microscale flow systems. Here, we propose an active mixing approach which enhances the mixing of viscoelastic fluid flow in a simplified pore T-junction structure. Mixing is actively controlled by modulating the driving pressure with a sinusoidal signal at the two inlets of the T-junction. The mixing effect is numerically investigated for both Newtonian and viscoelastic fluid flows under different pressure modulation conditions. The result shows that a degree of mixing as high as 0.9 is achieved in viscoelastic fluid flows through the T-junction mixer when the phase difference between the modulated pressures at the two inlets is 180°. This modulation method can also be used in other fluid mixing devices.

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A Planar Labyrinth Micromixer

2010 14th International Heat Transfer Conference, Volume 4 ◽

10.1115/ihtc14-22957 ◽

2010 ◽

Author(s):

Jeremy T. Cogswell ◽

Peng Li ◽

Mohammad Faghri

Keyword(s):

Soft Lithography ◽

Lab On A Chip ◽

Fluorescein Isothiocyanate ◽

Reynolds Numbers ◽

Mixing Efficiency ◽

Mixing Length ◽

Two Fluids ◽

Curved Channels ◽

Passive Mixing ◽

Important Challenge

Rapid mixing of two fluids in microchannels has posed an important challenge to the development of many integrated lab-on-a-chip systems. In this paper, we present a planar labyrinth micromixer (PLM) to achieve rapid and passive mixing by taking advantage of a synergistic combination of the Dean vortices in curved channels, a series of perturbation to the fluids from the sharp turns, and an expansion and contraction of the flow field via a circular chamber. The PLM is constructed in a single soft lithography step and the labyrinth has a footprint of 7.32 mm × 7.32 mm. Experiments using fluorescein isothiocyanate solutions and deionized water demonstrate that the design achieves fast and uniform mixing within 9.8 s to 32 ms for Reynolds numbers between 2.5 and 30. Compared to the mixing in the prevalent serpentine design, our design results in 38% and 79% improvements on the mixing efficiency at Re = 5 and Re = 30 respectively. An inverse relationship between mixing length and mass transfer Pe´clet number (Pe) is observed, which is superior to the logarithmic dependence of mixing length on Pe in chaotic mixers. Having a simple planar structure, the PLM can be easily integrated into lab-on-a-chip devices where passive mixing is needed.

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Automated High-Throughput System Combining Small-Scale Synthesis with Bioassays and Reaction Screening

SLAS TECHNOLOGY Translating Life Sciences Innovation ◽

10.1177/24726303211047839 ◽

2021 ◽

pp. 247263032110478

Author(s):

Nicolás M. Morato ◽

MyPhuong T. Le ◽

Dylan T. Holden ◽

R. Graham Cooks

Keyword(s):

High Throughput ◽

High Throughput Screening ◽

Desorption Electrospray Ionization ◽

Ambient Ionization ◽

Machine Learning Algorithms ◽

Small Scale ◽

Label Free ◽

Minimal Sample ◽

Secondary Droplets ◽

Automated Platform

The Purdue Make It system is a unique automated platform capable of small-scale in situ synthesis, screening small-molecule reactions, and performing direct label-free bioassays. The platform is based on desorption electrospray ionization (DESI), an ambient ionization method that allows for minimal sample workup and is capable of accelerating reactions in secondary droplets, thus conferring unique advantages compared with other high-throughput screening technologies. By combining DESI with liquid handling robotics, the system achieves throughputs of more than 1 sample/s, handling up to 6144 samples in a single run. As little as 100 fmol/spot of analyte is required to perform both initial analysis by mass spectrometry (MS) and further MSn structural characterization. The data obtained are processed using custom software so that results are easily visualized as interactive heatmaps of reaction plates based on the peak intensities of m/ z values of interest. In this paper, we review the system’s capabilities as described in previous publications and demonstrate its utilization in two new high-throughput campaigns: (1) the screening of 188 unique combinatorial reactions (24 reaction types, 188 unique reaction mixtures) to determine reactivity trends and (2) label-free studies of the nicotinamide N-methyltransferase enzyme directly from the bioassay buffer. The system’s versatility holds promise for several future directions, including the collection of secondary droplets containing the products from successful reaction screening measurements, the development of machine learning algorithms using data collected from compound library screening, and the adaption of a variety of relevant bioassays to high-throughput MS.

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Challenges in uncovering non-invasive biomarkers of endometriosis

Experimental Biology and Medicine ◽

10.1177/1535370220903270 ◽

2020 ◽

Vol 245 (5) ◽

pp. 437-447

Author(s):

Quanah J Hudson ◽

Alexandra Perricos ◽

Rene Wenzl ◽

Iveta Yotova

Keyword(s):

High Throughput Screening ◽

Large Scale ◽

Biomarker Discovery ◽

Current Knowledge ◽

Reproductive Age ◽

Small Scale ◽

Common Disease ◽

Sample Collection ◽

Childbearing Age ◽

Cohort Selection

Endometriosis affects up to 10% of women of childbearing age, causing symptoms that can include chronic pelvic pain and reduced fertility. The symptoms are not specific to the disease and can be confused with other gynecological conditions or normal menstruation. Currently, the disease can be only definitively diagnosed by laparoscopy, as no clinically accepted biomarker exists. Biomarker discovery can either follow a hypothesis-driven approach selecting targets to be tested based on current knowledge of the disease, or take an unbiased high-throughput screening “omics” approach, such as transcriptomics or proteomics, to identify markers that are unique or elevated in accessible bodily fluids of patients with the disease. Numerous studies have been conducted using these approaches to try and identify endometriosis biomarkers, but variabilities in study design, cohort selection, and analysis, together with the fact that most studies were small-scale, have made independent validation of biomarker candidates difficult. Therefore, efforts are underway to standardize cohort selection, patient data, and sample collection to allow better cross-study comparisons. Large scale multi-center studies using this standardized approach are necessary to validate existing endometriosis biomarker candidates and uncover potential new markers. Given the complexity and heterogeneity of the disease, it is likely that a panel of biomarkers will be necessary to diagnose and categorize endometriosis. Impact statement Endometriosis is a common disease affecting reproductive age women, which is associated with chronic pain and reduced fertility reducing the quality of life of many women. Definitive diagnosis requires invasive laparoscopic surgery creating a high barrier to diagnosis that can delay the onset of treatment significantly. Clinically approved biomarkers of endometriosis are currently lacking, making the discovery and validation of biomarkers that would lead to earlier diagnosis a priority for improving treatment of the disease.

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BIREFRINGENCE AND MAGNETO-OPTICAL PROPERTIES IN OLEIC ACID COATED Fe3O4 NANOPARTICLES: APPLICATION FOR OPTICAL SWITCH

International Journal of Nanoscience ◽

10.1142/s0219581x11008289 ◽

2011 ◽

Vol 10 (03) ◽

pp. 515-520 ◽

Cited By ~ 14

Author(s):

SI-HUA XIA ◽

JUN WANG ◽

ZHANG-XIAN LU ◽

FEIYAN ZHANG

Keyword(s):

Magnetic Field ◽

Optical Properties ◽

Oleic Acid ◽

Magnetic Nanoparticles ◽

Magnetic Nanoparticle ◽

Optical Switch ◽

Colloidal Suspension ◽

Experimental Parameters ◽

Nanoparticle Chains ◽

The Magnetic Field

We report magneto-optical properties in a kerosene colloidal suspension of oleic acid coated Fe3O4 nanoparticles (~14 nm). The magnetic colloids (fluids) show birefringence under a magnetic field. Systematical studies of the on–off switch times upon application of the on–off magnetic field with varied experimental parameters indicate that the switch response time depends strongly on the strength of the magnetic field and the concentration of the magnetic nanoparticles in the fluid. The data can be explained in terms of the formation of magnetic nanoparticle chains under a magnetic field. The important magneto-optical properties of the magnetic fluids allow us to design a tunable optical switch.

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Mass spectrometric detection of chlorophyll a and the tetrapyrrole secondary metabolite tolyporphin A in the filamentous cyanobacterium HT-58-2. Approaches to high-throughput screening of intact cyanobacteria

Journal of Porphyrins and Phthalocyanines ◽

10.1142/s108842461750078x ◽

2017 ◽

Vol 21 (11) ◽

pp. 759-768 ◽

Cited By ~ 5

Author(s):

Yunlong Zhang ◽

Ran Zhang ◽

Milad Nazari ◽

Michael C. Bagley ◽

Eric S. Miller ◽

...

Keyword(s):

High Throughput Screening ◽

Growth Period ◽

Mass Spectrometric ◽

Small Scale ◽

Spectrometric Analysis ◽

Microbial Culture ◽

Filamentous Cyanobacterium ◽

Intact Cells ◽

Chromatographic Fractionation ◽

Molecular Ion

Tolyporphins are unusual tetrapyrrole macrocycles produced by the filamentous cyanobacterium–microbial community HT-58-2, the only known source to date. Numerous cyanobacterial samples have been collected worldwide but most have not been screened for secondary metabolites. Identification of tolyporphins typically has entailed lipophilic extraction followed by chromatographic fractionation and spectroscopic and/or mass spectrometric analysis. For quantitation, lengthy lipophilic extraction, sample processing and HPLC separation are needed. Examination by MALDI-TOF-MS (with the matrix 1,5-diaminonaphthalene) of lipophilic crude extracts of small-scale HT-58-2 samples (2 mL) without chromatographic fractionation enabled semi-quantitation of tolyporphin A over a 41-day growth period. Screening for tolyporphin A in intact or slightly sheared and vortexed HT-58-2 samples (no lipophilic extraction), and confirmation of identity by tandem MS, were carried out by IR-MALDESI-FTMS. Tolyporphin A was identified by the molecular ion and four characteristic fragments. The molecular ion of chlorophyll [Formula: see text] also was observed. The sheared and vortexed sample contained substantial numbers of intact cells as demonstrated by regrowth of the filamentous cyanobacterium–microbial culture. The semi-quantitative and rapid qualitative methods developed herein should facilitate examination of other tolyporphin-producing organisms among the vast worldwide strains of cyanobacteria as well as investigation of the biosynthesis of tolyporphins.

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