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A special issue of Magnetochemistry (ISSN 2312-7481). This special issue belongs to the section "Applications of Magnetism and Magnetic Materials".

Deadline for manuscript submissions: closed (30 July 2022) | Viewed by 44459

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Dr. Marie Frenea-Robin

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Ampère Laboratory, Bioengineering Department, Ecole Centrale de Lyon, University Lyon 1, Bât H9 36 avenue Guy de Collongue, 69134 Ecully, France
Interests: microfluidics; contactless cell manipulation using different force fields; electromagnetic field interactions with biological systems
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Special Issue Information

Dear Colleagues,

Magnetic cell separation has become a key methodology for the isolation of target cell populations from biological suspensions, covering a wide spectrum of applications from diagnosis and therapy in biomedicine to environmental applications or fundamental research in biology. There now exists a great variety of commercially available separation instruments and reagents, which has permitted the rapid spread of the technology. However, there is still an increasing demand for new tools and protocols to improve the selectivity, yield, and sensitivity of the separation process while reducing its cost and providing a faster response. Moreover, the development of the technology is also driven by the need to develop robust solutions for the isolation of rare cells from complex mixtures (circulating tumor cells or hematopoietic stem cells in blood, pathogenic micro-organisms, bacteria belonging to the "rare biosphere", etc.). The answer to these challenges relies on interdisciplinary research combining fields such as microfluidics, magnetism, biology, chemistry, and materials science (engineered nanoparticles, permanent magnetic materials, magnetic polymer nanocomposites, etc.).

This Special Issue of Magnetochemistry aims to create a forum of discussion to share advances and address current challenges in magnetic cell separation. The topics listed below are meant as a guideline for possible contributions:

Cell separation devices:
a) Batch-type magnetic separators;
b) Optimized magnetic field sources for cell separation;
c) Microfluidic separation platforms based on magnetism.
Cell targeting and sorting strategies:
a) Cell labeling strategies;
b) Label-free separation methods based on magnetism;
c) Multifunctional nanoparticles for magnetic cell separation and detection.
Applications:
a) Translation into clinical and industrial practice;
b) Rare cell isolation;
c) Single cell isolation;
d) Environmental applications;
c) Other applications.

Dr. Marie Frenea-Robin
Guest Editor

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Keywords

magnetophoresis
continuous flow separation
rare cell isolation
magnetic labeling
micro-magnetofluidics

Published Papers (11 papers)

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Research

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14 pages, 3886 KiB

Open AccessArticle

Automated Immunomagnetic Enrichment and Optomicrofluidic Detection to Isolate Breast Cancer Cells: A Proof-of-Concept towards PoC Therapeutic Decision-Making

by Janis Stiefel, Michael Baßler, Jörn Wittek and Christian Freese

Magnetochemistry 2022, 8(9), 99; https://0-doi-org.brum.beds.ac.uk/10.3390/magnetochemistry8090099 - 06 Sep 2022

Viewed by 1795

Abstract

In breast cancer research, immunomagnetic enrichment of circulating tumor cells (CTCs) from body fluids has impressively evolved over the last decades. However, there is growing interest in further singularizing these pre-enriched rare cells to decrease signal-to-noise ratio for downstream molecular analysis, e.g., to distinguish between hormone receptor-associated tumor subtypes. This can be done by a combinatory principle to link magnetic cell separation with flow cytometry and single cell dispensing. We have recently introduced an automated benchtop platform with a microfluidic disposable cartridge to immunomagnetically enrich, fluorescence-based detect and dispense single cells from biological samples. Herein, we showcase the fine-tuning of microfluidic cell isolation in dependency of bead-binding on the cell surface. We implemented a gating function for the cytometer subunit of the benchtop platform to selectively dispense cells instead of autofluorescent objects. Finally, we developed a simplified qPCR protocol without RNA purification targeting breast cancer-relevant progesterone and estrogen receptor, Muc-1, Her-2, EpCAM and CXCR4 transcripts. In conclusion, the presented results markedly demonstrate a future diagnostic and therapy-accompanying semi-automated workflow using immunomagnetic enrichment, fluorescence-based isolation and dispensing of circulating tumor cells to achieve tumor subtyping by means of rapid, simple and immediate molecular biological examination of single cells. Full article

(This article belongs to the Special Issue Magnetic Cell Separation)

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15 pages, 1521 KiB

Open AccessArticle

Proof-of-Concept of a Novel Cell Separation Technology Using Magnetic Agarose-Based Beads

by Nils A. Brechmann, Märta Jansson, Alice Hägg, Ryan Hicks, Johan Hyllner, Kristofer Eriksson and Véronique Chotteau

Magnetochemistry 2022, 8(3), 34; https://0-doi-org.brum.beds.ac.uk/10.3390/magnetochemistry8030034 - 10 Mar 2022

Cited by 1 | Viewed by 4068

Abstract

The safety of the cells used for Advanced Therapy Medicinal Products is crucial for patients. Reliable methods for the cell purification are very important for the commercialization of those new therapies. With the large production scale envisioned for commercialization, the cell isolation methods need to be efficient, robust, operationally simple and generic while ensuring cell biological functionality and safety. In this study, we used high magnetized magnetic agarose-based beads conjugated with protein A to develop a new method for cell separation. A high separation efficiency of 91% yield and consistent isolation performances were demonstrated using population mixtures of human mesenchymal stem cells and HER2⁺ SKBR3 cells (80:20, 70:30 and 30:70). Additionally, high robustness against mechanical stress and minimal unspecific binding obtained with the protein A base conjugated magnetic beads were significant advantages in comparison with the same magnetic microparticles where the antibodies were covalently conjugated. This study provided insights on features of large high magnetized microparticles, which is promising for the large-scale application of cell purification. Full article

(This article belongs to the Special Issue Magnetic Cell Separation)

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16 pages, 2062 KiB

Open AccessFeature PaperArticle

Magnetic Enrichment of SARS-CoV-2 Antigen-Binding B Cells for Analysis of Transcriptome and Antibody Repertoire

by Maureen Banach, Isaac T. W. Harley, Mary K. McCarthy, Cody Rester, Adonis Stassinopoulos, Ross M. Kedl, Thomas E. Morrison and John C. Cambier

Magnetochemistry 2022, 8(2), 23; https://0-doi-org.brum.beds.ac.uk/10.3390/magnetochemistry8020023 - 05 Feb 2022

Cited by 2 | Viewed by 2908

Abstract

The ongoing COVID-19 pandemic has had devastating health impacts across the globe. The development of effective diagnostics and therapeutics will depend on the understanding of immune responses to natural infection and vaccination to the causative agent of COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While both B-cell immunity and T-cell immunity are generated in SARS-CoV-2-infected and vaccinated individuals, B-cell-secreted antibodies are known to neutralize SARS-CoV-2 virus and protect from the disease. Although interest in characterizing SARS-CoV-2-reactive B cells is great, the low frequency of antigen-binding B cells in human blood limits in-depth cellular profiling. To overcome this obstacle, we developed a magnetic bead-based approach to enrich SARS-CoV-2-reactive B cells prior to transcriptional and antibody repertoire analysis by single-cell RNA sequencing (scRNA-seq). Here, we describe isolation of SARS-CoV-2 antigen-binding B cells from two seropositive donors and comparison to nonspecific B cells from a seronegative donor. We demonstrate that SARS-CoV-2 antigen-binding B cells can be distinguished on the basis of transcriptional profile and antibody repertoire. Furthermore, SARS-CoV-2 antigen-binding B cells exhibit a gene expression pattern indicative of antigen experience and memory status. Combining scRNA-seq methods with magnetic enrichment enables the rapid characterization of SARS-CoV-2 antigen-binding B cells. Full article

(This article belongs to the Special Issue Magnetic Cell Separation)

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18 pages, 4231 KiB

Open AccessArticle

Continuous Flow Labeling and In-Line Magnetic Separation of Cells

by Zhixi Qian, Thomas R. Hanley, Lisa M. Reece, James F. Leary, Eugene D. Boland and Paul Todd

Magnetochemistry 2022, 8(1), 5; https://0-doi-org.brum.beds.ac.uk/10.3390/magnetochemistry8010005 - 30 Dec 2021

Cited by 1 | Viewed by 2470

Abstract

There is an identified need for point-of-care diagnostic systems for detecting and counting specific rare types of circulating cells in blood. By adequately labeling such cells with immunomagnetic beads and quantum dots, they can be efficiently collected magnetically for quantification using fluorescence methods. Automation of this process requires adequate mixing of the labeling materials with blood samples. A static mixing device can be employed to improve cell labeling efficiency and eliminate error-prone laboratory operations. Computational fluid dynamics (CFD) were utilized to simulate the flow of a labeling-materials/blood mixture through a 20-stage in-line static mixer of the interfacial-surface-generator type. Optimal fluid mixing conditions were identified and tested in a magnetic bead/tumor cell model, and it was found that labeled cells could be produced at 1.0 mL/min flow rate and fed directly into an in-line magnetic trap. The trap design consists of a dual flow channel with three bends and a permanent magnet positioned at the outer curve of each bend. The capture of labeled cells in the device was simulated using CFD, finite-element analysis and magnetophoretic mobility distributions of labeled cells. Testing with cultured CRL14777 human melanoma cells labeled with anti-CD146 1.5 μm diameter beads indicated that 90 ± 10% are captured at the first stage, and these cells can be captured when present in whole blood. Both in-line devices were demonstrated to function separately and together as predicted. Full article

(This article belongs to the Special Issue Magnetic Cell Separation)

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14 pages, 3622 KiB

Open AccessArticle

SSEA-4 Antigen Is Expressed on Rabbit Lymphocyte Subsets

by Jaromír Vašíček, Andrej Baláži, Miroslav Bauer and Peter Chrenek

Magnetochemistry 2021, 7(7), 94; https://0-doi-org.brum.beds.ac.uk/10.3390/magnetochemistry7070094 - 27 Jun 2021

Viewed by 2033

Abstract

SSEA-4 antigen can be mainly found in embryos and embryonic stem cells. However, its expression has been observed also in adult stem and progenitor cells, or even in some differentiated cells. Moreover, we found a considerable number of SSEA-4 positive (SSEA-4⁺) cells within the rabbit peripheral blood and bone marrow mononuclear cells (PBMCs and BMMCs) in our previous study. Since no information about such cells can be found anywhere in the literature, the aim of this study was to identify their origin. At first, phenotypic analyses of fresh rabbit PBMCs and BMMCs were performed using flow cytometry and specific antibodies against SSEA-4 and leukocyte subsets. Then, SSEA-4⁺ were enriched using magnetic activated cell sorting (MACS) and analyzed for their phenotype using qPCR. We found significant SSEA-4⁺ cell population in PBMCs (~50%) and BMMCs (~20%). All those cells co-expressed CD45 and a majority of them also expressed B-cell marker (IgM; 50% of SSEA-4⁺ PBMCs and 60% of SSEA-4⁺ BMMCs). Increased (p < 0.05) expression of SSEA-4, CD45 and B-cell markers (IgM, CD79α and MHCII) were also noticed by qPCR in SSEA-4⁺ cells enriched via MACS (with efficiency over 80%). Both methods did not detect significant expression of monocyte or T-cell markers. In conclusion, SSEA-4⁺ cells in rabbit blood and bone marrow are of hematopoietic origin and probably belong to B-lineage cells as possessing the phenotype of B lymphocytes. However, the true function of SSEA-4 antigen in these cells should be explored by further studies. Full article

(This article belongs to the Special Issue Magnetic Cell Separation)

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13 pages, 2507 KiB

Open AccessArticle

The Effect of pH and Viscosity on Magnetophoretic Separation of Iron Oxide Nanoparticles

by Leonie Wittmann, Chiara Turrina and Sebastian P. Schwaminger

Magnetochemistry 2021, 7(6), 80; https://0-doi-org.brum.beds.ac.uk/10.3390/magnetochemistry7060080 - 03 Jun 2021

Cited by 17 | Viewed by 3500

Abstract

Magnetic nanoparticles (MNPs) are used for magnetophoresis-based separation processes in various biomedical and engineering applications. Essential requirements are the colloidal stability of the MNPs and the ability to be separated even in low magnetic field gradients. Bare iron oxide nanoparticles (BIONs) with a diameter of 9.2 nm are synthesized via coprecipitation, exhibiting a high saturation magnetization of 70.84 Am² kg⁻¹ and no remanence. In our study, zeta potential, dynamic light scattering (DLS), and sedimentation analysis show that the aggregation behavior of BIONs is influenced by pH and viscosity. Small aggregate clusters are formed with either low or high pH values or increased viscosity. Regarding magnetophoresis-based separation, a higher viscosity leads to lower magnetophoretic velocities, similar to how small aggregates do. Additionally, cooperative magnetophoresis, the joint motion of strongly interacting particles, affects the separation of the BIONs, too. Our study emphasizes the effect of pH and viscosity on the physicochemical characteristics of MNPs, resulting in different aggregation behavior. Particularly, for high viscous working media in downstream processing and medicine, respectively, the viscosity should be taken into account, as it will affect particle migration. Full article

(This article belongs to the Special Issue Magnetic Cell Separation)

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15 pages, 3733 KiB

Open AccessArticle

Enrichment of Rabbit Primitive Hematopoietic Cells via MACS Depletion of CD45⁺ Bone Marrow Cells

by Jaromír Vašíček, Andrej Baláži, Miroslav Bauer, Andrea Svoradová, Mária Tirpáková, Ľubomír Ondruška, Vladimír Parkányi, Alexander V. Makarevich and Peter Chrenek

Magnetochemistry 2021, 7(1), 11; https://0-doi-org.brum.beds.ac.uk/10.3390/magnetochemistry7010011 - 13 Jan 2021

Cited by 1 | Viewed by 2779

Abstract

Hematopoietic stem and progenitor cells (HSC/HPCs) of human or few animal species have been studied for over 30 years. However, there is no information about rabbit HSC/HPCs, although they might be a valuable animal model for studying human hematopoietic disorders or could serve as genetic resource for the preservation of animal biodiversity. CD34 marker is commonly used to isolate HSC/HPCs. Due to unavailability of specific anti-rabbit CD34 antibodies, a novel strategy for the isolation and enrichment of rabbit HSC/HPCs was used in this study. Briefly, rabbit bone marrow mononuclear cells (BMMCs) were sorted immunomagnetically in order to remove all mature (CD45⁺) cells. The cells were depleted with overall purity about 60–70% and then cultured in a special medium designed for the expansion of CD34⁺ cells. Quantitative Polymerase Chain Reaction (qPCR) analysis confirmed the enrichment of primitive hematopoietic cells, as the expression of CD34 and CD49f increased (p < 0.05) and CD45 decreased (p < 0.001) at the end of culture in comparison to fresh BMMCs. However, cell culture still exhibited the presence of CD45⁺ cells, as identified by flow cytometry. After gating on CD45⁻ cells the MHCI⁺MHCII⁻CD38⁺CD49f⁺CD90⁻CD117⁻ phenotype was observed. In conclusion, rabbit HSC/HPCs might be isolated and enriched by the presented method. However, further optimization is still required. Full article

(This article belongs to the Special Issue Magnetic Cell Separation)

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Review

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45 pages, 10369 KiB

Open AccessReview

Basic Principles and Recent Advances in Magnetic Cell Separation

by Marie Frenea-Robin and Julien Marchalot

Magnetochemistry 2022, 8(1), 11; https://0-doi-org.brum.beds.ac.uk/10.3390/magnetochemistry8010011 - 14 Jan 2022

Cited by 40 | Viewed by 12916

Abstract

Magnetic cell separation has become a key methodology for the isolation of target cell populations from biological suspensions, covering a wide spectrum of applications from diagnosis and therapy in biomedicine to environmental applications or fundamental research in biology. There now exists a great variety of commercially available separation instruments and reagents, which has permitted rapid dissemination of the technology. However, there is still an increasing demand for new tools and protocols which provide improved selectivity, yield and sensitivity of the separation process while reducing cost and providing a faster response. This review aims to introduce basic principles of magnetic cell separation for the neophyte, while giving an overview of recent research in the field, from the development of new cell labeling strategies to the design of integrated microfluidic cell sorters and of point-of-care platforms combining cell selection, capture, and downstream detection. Finally, we focus on clinical, industrial and environmental applications where magnetic cell separation strategies are amongst the most promising techniques to address the challenges of isolating rare cells. Full article

(This article belongs to the Special Issue Magnetic Cell Separation)

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19 pages, 5337 KiB

Open AccessReview

The Origins and the Current Applications of Microfluidics-Based Magnetic Cell Separation Technologies

by Ozgun Civelekoglu, A. Bruno Frazier and A. Fatih Sarioglu

Magnetochemistry 2022, 8(1), 10; https://0-doi-org.brum.beds.ac.uk/10.3390/magnetochemistry8010010 - 11 Jan 2022

Cited by 8 | Viewed by 3465

Abstract

The magnetic separation of cells based on certain traits has a wide range of applications in microbiology, immunology, oncology, and hematology. Compared to bulk separation, performing magnetophoresis at micro scale presents advantages such as precise control of the environment, larger magnetic gradients in miniaturized dimensions, operational simplicity, system portability, high-throughput analysis, and lower costs. Since the first integration of magnetophoresis and microfluidics, many different approaches have been proposed to magnetically separate cells from suspensions at the micro scale. This review paper aims to provide an overview of the origins of microfluidic devices for magnetic cell separation and the recent technologies and applications grouped by the targeted cell types. For each application, exemplary experimental methods and results are discussed. Full article

(This article belongs to the Special Issue Magnetic Cell Separation)

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16 pages, 2437 KiB

Open AccessFeature PaperReview

Magnetic Polymers for Magnetophoretic Separation in Microfluidic Devices

by Lucie Descamps, Damien Le Roy, Caterina Tomba and Anne-laure Deman

Magnetochemistry 2021, 7(7), 100; https://0-doi-org.brum.beds.ac.uk/10.3390/magnetochemistry7070100 - 08 Jul 2021

Cited by 17 | Viewed by 3853

Abstract

Magnetophoresis offers many advantages for manipulating magnetic targets in microsystems. The integration of micro-flux concentrators and micro-magnets allows achieving large field gradients and therefore large reachable magnetic forces. However, the associated fabrication techniques are often complex and costly, and besides, they put specific constraints on the geometries. Magnetic composite polymers provide a promising alternative in terms of simplicity and fabrication costs, and they open new perspectives for the microstructuring, design, and integration of magnetic functions. In this review, we propose a state of the art of research works implementing magnetic polymers to trap or sort magnetic micro-beads or magnetically labeled cells in microfluidic devices. Full article

(This article belongs to the Special Issue Magnetic Cell Separation)

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Other

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12 pages, 2546 KiB

Open AccessProtocol

Enrichment and Detection of Antigen-Binding B Cells for Mass Cytometry

by Zachary C. Stensland and Mia J. Smith

Magnetochemistry 2021, 7(7), 92; https://0-doi-org.brum.beds.ac.uk/10.3390/magnetochemistry7070092 - 23 Jun 2021

Cited by 6 | Viewed by 2902

Abstract

Over the years, various techniques have been utilized to study the function and phenotype of antigen-binding B cells in the primary repertoire following immunization, infection, and development of autoimmunity. Due to the low frequency of antigen-reactive B cells (<0.05% of lymphocytes) in the periphery, preliminary enrichment of cells is necessary to achieve sufficient numbers for statistically sound characterization, especially when downstream analytic platform use, e.g., CyTOF, is low throughput. We previously described a method to detect and enrich antigen-reactive B cells from peripheral blood and tissues using biotinylated antigens in conjunction with magnetic nanoparticles, preparative to a downstream analysis by ELISPOT and flow cytometry. While mass cytometry (CyTOF) enables high dimensional immunophenotyping of over 40 unique parameters on a single-cell level, its low throughput compared to flow cytometry and requirement for removal of metal contaminants, such as nanoparticles, made it particularly unsuitable for studies of rare cells in a mixed population. Here we describe a novel CyTOF-compatible approach for multiplexed enrichment of antigen-reactive B cells, e.g., insulin and tetanus toxoid, using cleavable magnetic nanoparticles. This method allows improved monitoring of the phenotype and function of antigen-reactive B cells during the development of disease or after immunization while minimizing the amount of sample and run times needed. Full article

(This article belongs to the Special Issue Magnetic Cell Separation)

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