Browse
Submit Data
Databases
API
Help

Dataset Information

38 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Microfluidic deformability-activated sorting of single particles.

ABSTRACT: Mechanical properties have emerged as a significant label-free marker for characterizing deformable particles such as cells. Here, we demonstrated the first single-particle-resolved, cytometry-like deformability-activated sorting in the continuous flow on a microfluidic chip. Compared with existing deformability-based sorting techniques, the microfluidic device presented in this work measures the deformability and immediately sorts the particles one-by-one in real time. It integrates the transit-time-based deformability measurement and active hydrodynamic sorting onto a single chip. We identified the critical factors that affect the sorting dynamics by modeling and experimental approaches. We found that the device throughput is determined by the summation of the sensing, buffering, and sorting time. A total time of ~100 ms is used for analyzing and sorting a single particle, leading to a throughput of 600 particles/min. We synthesized poly(ethylene glycol) diacrylate (PEGDA) hydrogel beads as the deformability model for device validation and performance evaluation. A deformability-activated sorting purity of 88% and an average efficiency of 73% were achieved. We anticipate that the ability to actively measure and sort individual particles one-by-one in a continuous flow would find applications in cell-mechanotyping studies such as correlational studies of the cell mechanical phenotype and molecular mechanism.

SUBMITTER: Choi G

PROVIDER: S-EPMC8433438 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Deformability based Cell Sorting using Microfluidic Ratchets Enabling Phenotypic Separation of Leukocytes Directly from Whole Blood.

Project description:The separation of leukocytes from whole blood is a prerequisite for many biological assays. Traditional methods require significant sample volumes and are often undesirable because they expose leukocytes to harsh physical or chemical treatment. Existing microfluidic approaches can work with smaller volumes, but lack selectivity. In particular, the selectivity of microfluidic systems based on microfiltration is limited by fouling due to clogging. Here, we developed a method to separate leukocytes from whole blood using the microfluidic ratchet mechanism, which filters the blood sample using a matrix of micrometer-scale tapered constrictions. Deforming single cells through such constrictions requires directionally asymmetrical forces, which enables oscillatory flow to create a ratcheting transport that depends on cell size and deformability. Simultaneously, oscillatory flow continuously agitates the cells to limit the contact time with the filter microstructure to prevent adsorption and clogging. We show this device is capable of isolating leukocytes from whole blood with 100% purity (i.e. no contaminant erythrocytes) and <2% leukocytes loss. We further demonstrate the potential to phenotypically sort leukocytes to enrich for granulocytes and lymphocytes subpopulations. Together, this process provides a sensitive method to isolate and sort leukocytes directly from whole blood based on their biophysical properties.

| S-EPMC5529452 | biostudies-literature

Microfluidic electrical sorting of particles based on shape in a spiral microchannel.

Project description:Shape is an intrinsic marker of cell cycle, an important factor for identifying a bioparticle, and also a useful indicator of cell state for disease diagnostics. Therefore, shape can be a specific marker in label-free particle and cell separation for various chemical and biological applications. We demonstrate in this work a continuous-flow electrical sorting of spherical and peanut-shaped particles of similar volumes in an asymmetric double-spiral microchannel. It exploits curvature-induced dielectrophoresis to focus particles to a tight stream in the first spiral without any sheath flow and subsequently displace them to shape-dependent flow paths in the second spiral without any external force. We also develop a numerical model to simulate and understand this shape-based particle sorting in spiral microchannels. The predicted particle trajectories agree qualitatively with the experimental observation.

| S-EPMC3977798 | biostudies-other

Affordable Microfluidic Bead-Sorting Platform for Automated Selection of Porous Particles Functionalized with Bioactive Compounds.

Project description:The ability to rapidly and accurately evaluate bioactive compounds immobilized on porous particles is crucial in the discovery of drugs, diagnostic reagents, ligands, and catalysts. Existing options for solid phase screening of bioactive compounds, while highly effective and well established, can be cost-prohibitive for proof-of-concept and early stage work, limiting its applicability and flexibility in new research areas. Here, we present a low-cost microfluidics-based platform enabling automated screening of small porous beads from solid-phase peptide libraries with high sensitivity and specificity, to identify leads with high binding affinity for a biological target. The integration of unbiased computer assisted image processing and analysis tools, provided the platform with the flexibility of sorting through beads with distinct fluorescence patterns. The customized design of the microfluidic device helped with handling beads with different diameters (~100-300 µm). As a microfluidic device, this portable novel platform can be integrated with a variety of analytical instruments to perform screening. In this study, the system utilizes fluorescence microscopy and unsupervised image analysis, and can operate at a sorting speed of up to 125 beads/hr (~3.5 times faster than a trained operator) providing >90% yield and >90% bead sorting accuracy. Notably, the device has proven successful in screening a model solid-phase peptide library by showing the ability to select beads carrying peptides binding a target protein (human IgG).

| S-EPMC6510793 | biostudies-literature

Microfluidic high-throughput encapsulation and hydrodynamic self-sorting of single cells.

Project description:We present a purely hydrodynamic method for the high-throughput encapsulation of single cells into picoliter droplets, and spontaneous self-sorting of these droplets. Encapsulation uses a cell-triggered Rayleigh-Plateau instability in a flow-focusing geometry, and self-sorting puts to work two extra hydrodynamic mechanisms: lateral drift of deformable objects in a shear flow, and sterically driven dispersion in a compressional flow. Encapsulation and sorting are achieved on-flight in continuous flow at a rate up to 160 cells per second. The whole process is robust and cost-effective, involving no optical or electrical discrimination, active sorting, flow switching, or moving parts. Successful encapsulation and sorting of 70-80% of the injected cell population into drops containing one and only one cell, with <1% contamination by empty droplets, is demonstrated. The system is also applied to the direct encapsulation and sorting of cancerous lymphocytes from a whole blood mixture, yielding individually encapsulated cancer cells with a >10,000-fold enrichment as compared with the initial mix. The method can be implemented in simple "soft lithography" chips, allowing for easy downstream coupling with microfluidic cell biology or molecular biology protocols.

| S-EPMC2265149 | biostudies-literature

Accurately tracking single-cell movement trajectories in microfluidic cell sorting devices.

Project description:Microfluidics are routinely used to study cellular properties, including the efficient quantification of single-cell biomechanics and label-free cell sorting based on the biomechanical properties, such as elasticity, viscosity, stiffness, and adhesion. Both quantification and sorting applications require optimal design of the microfluidic devices and mathematical modeling of the interactions between cells, fluid, and the channel of the device. As a first step toward building such a mathematical model, we collected video recordings of cells moving through a ridged microfluidic channel designed to compress and redirect cells according to cell biomechanics. We developed an efficient algorithm that automatically and accurately tracked the cell trajectories in the recordings. We tested the algorithm on recordings of cells with different stiffness, and showed the correlation between cell stiffness and the tracked trajectories. Moreover, the tracking algorithm successfully picked up subtle differences of cell motion when passing through consecutive ridges. The algorithm for accurately tracking cell trajectories paves the way for future efforts of modeling the flow, forces, and dynamics of cell properties in microfluidics applications.

| S-EPMC5802930 | biostudies-literature

Fluorescence-Activated Droplet Sorting for Single-Cell Directed Evolution.

Project description:Synthetic biology aims to improve human health and the environment by repurposing biological enzymes for use in practical applications. However, natural enzymes often function with suboptimal activity when engineered into biological pathways or challenged to recognize unnatural substrates. Overcoming this problem requires efficient directed evolution methods for discovering new enzyme variants that function with a desired activity. Here, we describe the construction, validation, and application of a fluorescence-activated droplet sorting (FADS) instrument that was established to evolve enzymes for synthesizing and modifying artificial genetic polymers (XNAs). The microfluidic system enables droplet sorting at ?2-3 kHz using fluorescent sensors that are responsive to enzymatic activity. The ability to evolve nucleic acid enzymes with customized properties will uniquely drive emerging applications in synthetic biology, biotechnology, and healthcare.

| S-EPMC6942126 | biostudies-literature

Developments in label-free microfluidic methods for single-cell analysis and sorting.

Project description:Advancements in microfluidic technologies have led to the development of many new tools for both the characterization and sorting of single cells without the need for exogenous labels. Label-free microfluidics reduce the preparation time, reagents needed, and cost of conventional methods based on fluorescent or magnetic labels. Furthermore, these devices enable analysis of cell properties such as mechanical phenotype and dielectric parameters that cannot be characterized with traditional labels. Some of the most promising technologies for current and future development toward label-free, single-cell analysis and sorting include electronic sensors such as Coulter counters and electrical impedance cytometry; deformation analysis using optical traps and deformation cytometry; hydrodynamic sorting such as deterministic lateral displacement, inertial focusing, and microvortex trapping; and acoustic sorting using traveling or standing surface acoustic waves. These label-free microfluidic methods have been used to screen, sort, and analyze cells for a wide range of biomedical and clinical applications, including cell cycle monitoring, rapid complete blood counts, cancer diagnosis, metastatic progression monitoring, HIV and parasite detection, circulating tumor cell isolation, and point-of-care diagnostics. Because of the versatility of label-free methods for characterization and sorting, the low-cost nature of microfluidics, and the rapid prototyping capabilities of modern microfabrication, we expect this class of technology to continue to be an area of high research interest going forward. New developments in this field will contribute to the ongoing paradigm shift in cell analysis and sorting technologies toward label-free microfluidic devices, enabling new capabilities in biomedical research tools as well as clinical diagnostics. This article is categorized under: Diagnostic Tools > Biosensing Diagnostic Tools > Diagnostic Nanodevices.

| S-EPMC6200655 | biostudies-literature

Design of a Microfluidic Chip for Magnetic-Activated Sorting of One-Bead-One-Compound Libraries.

Project description:Molecular targeting using ligands specific to disease markers has shown great promise for early detection and directed therapy. Bead-based combinatorial libraries have served as powerful tools for the discovery of novel targeting agents. Screening platforms employing magnetic capture have been used to achieve rapid and efficient identification of high-affinity ligands from one-bead-one-compound (OBOC) libraries. Traditional manual methodologies to isolate magnetized "hit" beads are tedious and lack accuracy, and existing instruments to expedite bead sorting tend to be costly and complex. Here, we describe the design and construction of a simple and inexpensive microfluidic magnetic sorting device using standard photolithography and soft lithography approaches to facilitate high-throughput isolation of magnetized positive hit beads from combinatorial libraries. We have demonstrated that the device is able to sort magnetized beads with superior accuracy compared to conventional manual sorting approaches. This chip offers a very convenient yet inexpensive alternative for screening OBOC libraries.

| S-EPMC5321554 | biostudies-literature

Controlled Manipulation and Active Sorting of Particles Inside Microfluidic Chips Using Bulk Acoustic Waves and Machine Learning.

Project description:Manipulation of cells, droplets, and particles via ultrasound within microfluidic chips is a rapidly growing field, with applications in cell and particle sorting, blood fractionation, droplet transport, and enrichment of rare or cancerous cells, among others. However, current methods with a single ultrasonic transducer offer limited control of the position of single particles. In this paper, we demonstrate closed-loop two-dimensional manipulation of particles inside closed-channel microfluidic chips, by controlling the frequency of a single ultrasound transducer, based on machine-vision-measured positions of the particles. For the control task, we propose using algorithms derived from the family of multi-armed bandit algorithms. We show that these algorithms can achieve controlled manipulation with no prior information on the acoustic field shapes. The method learns as it goes: there is no need to restart the experiment at any point. Starting with no knowledge of the field shapes, the algorithms can (eventually) move a particle from one position inside the chamber to another. This makes the method very robust to changes in chip and particle properties. We demonstrate that the method can be used to manipulate a single particle, three particles simultaneously, and also a single particle in the presence of a bubble in the chip. Finally, we demonstrate the practical applications of this method in active sorting of particles, by guiding each particle to exit the chip through one of three different outlets at will. Because the method requires no model or calibration, the work paves the way toward the acoustic manipulation of microparticles inside unstructured environments.

| S-EPMC8154862 | biostudies-literature

Microfluidic sorting of microtissues.

Project description:Increasingly, invitro culture of adherent cell types utilizes three-dimensional (3D) scaffolds or aggregate culture strategies to mimic tissue-like, microenvironmental conditions. In parallel, new flow cytometry-based technologies are emerging to accurately analyze the composition and function of these microtissues (i.e., large particles) in a non-invasive and high-throughput way. Lacking, however, is an accessible platform that can be used to effectively sort or purify large particles based on analysis parameters. Here we describe a microfluidic-based, electromechanical approach to sort large particles. Specifically, sheath-less asymmetric curving channels were employed to separate and hydrodynamically focus particles to be analyzed and subsequently sorted. This design was developed and characterized based on wall shear stress, tortuosity of the flow path, vorticity of the fluid in the channel, sorting efficiency and enrichment ratio. The large particle sorting device was capable of purifying fluorescently labelled embryoid bodies (EBs) from unlabelled EBs with an efficiency of 87.3% ± 13.5%, and enrichment ratio of 12.2 ± 8.4 (n = 8), while preserving cell viability, differentiation potential, and long-term function.

| S-EPMC3324260 | biostudies-other

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data