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Micromachines
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Blood-on-a-Chip
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Blood-on-a-Chip

A special issue of Micromachines (ISSN 2072-666X). This special issue belongs to the section "B：Biology and Biomedicine".

Deadline for manuscript submissions: closed (31 May 2020) | Viewed by 32758

Special Issue Editor

Dr. Andries D. van der Meer

E-Mail Website
Guest Editor
Applied Stem Cell Technologies, University of Twente, PO Box 217, 7500 AE Enschede, The Netherlands
Interests: microfluidics; microphysiological systems; organs-on-chips; diagnostics; disease modeling; thrombosis; coagulation; lab-on-a-chip; biophysics; fluid dynamics

Special Issue Information

Dear Colleagues,

It is with great pleasure that I invite you to contribute to the Special Issue of Micromachines on ‘Blood-on-a-Chip’, in which we will focus on the integration, manipulation, and analysis of blood and its components in microengineered systems.

Blood flows through almost every organ and tissue in our body, transporting molecules, cells, gases, ions, nutrients, and waste from one part of the system to the other. As such, our blood offers a unique window on systemic health and disease, and therefore has great clinical and diagnostic value. Importantly, only limited volumes of blood are available for analysis, particularly in specific patient subgroups like premature infants and sepsis patients. Moreover, the analyte of interest can sometimes be quite rare, as is the case in, e.g., specific cell-free DNAs, cytokines, or circulating tumor cells. Microdevices are uniquely suited to address these challenges by enabling the handling and analysis of small volumes of liquid. Many examples exist of biomedical microdevices based on lab-on-a-chip and biosensor technology that allow analysis of blood or its components, either in laboratory settings, or even in point-of-care applications.

The fluid dynamics of blood is intricately tied to its function and to its role in disease; 25% of all deaths worldwide are due to acute problems in blood flow, such as thrombosis, embolism or bleeding. Microfluidic devices offer unique opportunities to study blood or its components in well-controlled dynamic conditions and allow us to gain a deeper understanding of the relevant biophysical processes in hemostasis, thrombosis, and inflammation. Recently, many advances have been made in flowing blood through microfluidic chips that contain cultured human tissues, including vascular tissue. Such ‘microphysiological systems’ truly integrate microengineered components as well as living cells and tissues, including flowing human blood, thereby capturing tissue-level—and sometimes organ-level—functionality. These integrated microsystems, also known as ‘organs-on-chips’, are currently being applied in disease modeling, drug development and food safety testing.

The rapid developments in studying human blood with microsystems means that current and future microtechnical innovations will enable us to gain an even deeper understanding of human health and disease. For this Special Issue of Micromachines on ‘Blood-on-a-Chip’, I wholeheartedly invite you to submit and share your latest results related to studying human blood in engineered microsystems. I look forward to your contributions!

Dr. Andries D. van der Meer
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Micromachines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2100 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Microfluidics
  • Hematology
  • Point-of-care
  • Biomedical microdevices
  • Diagnostics
  • Disease modeling
  • Lab-on-a-chip
  • Biophysics
  • Fluid dynamics
  • Pharmacology
  • Blood
  • Platelets
  • PBMC
  • Endothelium
  • Microphysiological systems
  • Organs-on-chips
  • Inflammation
  • Thrombosis
  • Coagulation
  • Transport
  • Biosensing
  • Micropumps
  • Image analysis

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Published Papers (6 papers)

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Research

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12 pages, 1808 KiB  
Article
Influence of Hydrodynamics and Hematocrit on Ultrasound-Induced Blood Plasmapheresis
by Itziar González, Roque Rubén Andrés, Alberto Pinto and Pilar Carreras
Micromachines 2020, 11(8), 751; https://doi.org/10.3390/mi11080751 - 31 Jul 2020
Cited by 9 | Viewed by 3254
Abstract
Acoustophoretic blood plasma separation is based on cell enrichment processes driven by acoustic radiation forces. The combined influence of hematocrit and hydrodynamics has not yet been quantified in the literature for these processes acoustically induced on blood. In this paper, we present an [...] Read more.
Acoustophoretic blood plasma separation is based on cell enrichment processes driven by acoustic radiation forces. The combined influence of hematocrit and hydrodynamics has not yet been quantified in the literature for these processes acoustically induced on blood. In this paper, we present an experimental study of blood samples exposed to ultrasonic standing waves at different hematocrit percentages and hydrodynamic conditions, in order to enlighten their individual influence on the acoustic response of the samples. The experiments were performed in a glass capillary (700 µm-square cross section) actuated by a piezoelectric ceramic at a frequency of 1.153 MHz, hosting 2D orthogonal half-wavelength resonances transverse to the channel length, with a single-pressure-node along its central axis. Different hematocrit percentages Hct = 2.25%, 4.50%, 9.00%, and 22.50%, were tested at eight flow rate conditions of Q = 0:80 µL/min. Cells were collected along the central axis driven by the acoustic radiation force, releasing plasma progressively free of cells. The study shows an optimal performance in a flow rate interval between 20 and 80 µL/min for low hematocrit percentages Hct ≤ 9.0%, which required very short times close to 10 s to achieve cell-free plasma in percentages over 90%. This study opens new lines for low-cost personalized blood diagnosis. Full article
(This article belongs to the Special Issue Blood-on-a-Chip)
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11 pages, 2892 KiB  
Article
Adsorption and Absorption of Collagen Peptides to Polydimethlysiloxane and Its Influence on Platelet Adhesion Flow Assays
by Matthew G. Sorrells and Keith B. Neeves
Micromachines 2020, 11(1), 62; https://doi.org/10.3390/mi11010062 - 5 Jan 2020
Cited by 3 | Viewed by 4512
Abstract
Collagen peptides are an alternative to animal derived collagens for platelet function studies under flow. The purpose of this study was to examine the use of collagen peptides in polydimethylsiloxane (PDMS) devices. Three collagen peptides with amino acid sequences and structures that capture [...] Read more.
Collagen peptides are an alternative to animal derived collagens for platelet function studies under flow. The purpose of this study was to examine the use of collagen peptides in polydimethylsiloxane (PDMS) devices. Three collagen peptides with amino acid sequences and structures that capture von Willebrand factor and bind it with the platelet receptors integrin α2β1 and glycoprotein VI were patterned on glass, silicon, and PDMS. Each of these surfaces was also functionalized with tridecafluoro-1,1,2,2-tetrahydrooctyltrichlorosilane (FOTS). Surfaces were characterized by their ability to support platelet adhesion, topology by atomic force microscopy, contact angle, and peptides absorption. PDMS readily absorbs collagen peptides, depleting them from solution, thus reducing their adsorption to glass and silicon substrates when used for micropatterning. Treatment of PDMS with FOTS, but not bovine serum albumin or poloxamer 407, inhibits collagen peptide absorption and supports adsorption and platelet adhesion at venous and arterial shear rates. Similarly, FOTS treatment of glass or silicon supports collagen peptide adsorption even in the presence of untreated PDMS. In conclusion, PDMS acts as an absorptive sink for collagen peptides, rendering a non-adhesive surface for platelet adhesion and competing for peptides when used for micropatterning. The absorption of collagen peptides can be overcome by functionalization of PDMS with a fluorinated alkyl silane, thus allowing its use as a material for micropatterning or as a surface for platelet adhesion flow assays. Full article
(This article belongs to the Special Issue Blood-on-a-Chip)
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22 pages, 9378 KiB  
Article
3D Sugar Printing of Networks Mimicking the Vasculature
by Andreas M. A. O. Pollet, Erik F. G. A. Homburg, Ruth Cardinaels and Jaap M. J. den Toonder
Micromachines 2020, 11(1), 43; https://doi.org/10.3390/mi11010043 - 30 Dec 2019
Cited by 19 | Viewed by 4534
Abstract
The vasculature plays a central role as the highway of the body, through which nutrients and oxygen as well as biochemical factors and signals are distributed by blood flow. Therefore, understanding the flow and distribution of particles inside the vasculature is valuable both [...] Read more.
The vasculature plays a central role as the highway of the body, through which nutrients and oxygen as well as biochemical factors and signals are distributed by blood flow. Therefore, understanding the flow and distribution of particles inside the vasculature is valuable both in healthy and disease-associated networks. By creating models that mimic the microvasculature fundamental knowledge can be obtained about these parameters. However, microfabrication of such models remains a challenging goal. In this paper we demonstrate a promising 3D sugar printing method that is capable of recapitulating the vascular network geometry with a vessel diameter range of 1 mm down to 150 µm. For this work a dedicated 3D printing setup was built that is capable of accurately printing the sugar glass material with control over fibre diameter and shape. By casting of printed sugar glass networks in PDMS and dissolving the sugar glass, perfusable networks with circular cross-sectional channels are obtained. Using particle image velocimetry, analysis of the flow behaviour was conducted showing a Poisseuille flow profile inside the network and validating the quality of the printing process. Full article
(This article belongs to the Special Issue Blood-on-a-Chip)
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13 pages, 3837 KiB  
Communication
Automated Analysis of Platelet Aggregation on Cultured Endothelium in a Microfluidic Chip Perfused with Human Whole Blood
by Hugo J. Albers, Robert Passier, Albert van den Berg and Andries D. van der Meer
Micromachines 2019, 10(11), 781; https://doi.org/10.3390/mi10110781 - 14 Nov 2019
Cited by 13 | Viewed by 6262
Abstract
Organ-on-a-chip models with incorporated vasculature are becoming more popular to study platelet biology. A large variety of image analysis techniques are currently used to determine platelet coverage, ranging from manually setting thresholds to scoring platelet aggregates. In this communication, an automated methodology is [...] Read more.
Organ-on-a-chip models with incorporated vasculature are becoming more popular to study platelet biology. A large variety of image analysis techniques are currently used to determine platelet coverage, ranging from manually setting thresholds to scoring platelet aggregates. In this communication, an automated methodology is introduced, which corrects misalignment of a microfluidic channel, automatically defines regions of interest and utilizes a triangle threshold to determine platelet coverages and platelet aggregate size distributions. A comparison between the automated methodology and manual identification of platelet aggregates shows a high accuracy of the triangle methodology. Furthermore, the image analysis methodology can determine platelet coverages and platelet size distributions in microfluidic channels lined with either untreated or activated endothelium used for whole blood perfusion, proving the robustness of the method. Full article
(This article belongs to the Special Issue Blood-on-a-Chip)
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Review

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27 pages, 1546 KiB  
Review
Vascularized Microfluidics and the Blood–Endothelium Interface
by Christopher A. Hesh, Yongzhi Qiu and Wilbur A. Lam
Micromachines 2020, 11(1), 18; https://doi.org/10.3390/mi11010018 - 23 Dec 2019
Cited by 31 | Viewed by 5608
Abstract
The microvasculature is the primary conduit through which the human body transmits oxygen, nutrients, and other biological information to its peripheral tissues. It does this through bidirectional communication between the blood, consisting of plasma and non-adherent cells, and the microvascular endothelium. Current understanding [...] Read more.
The microvasculature is the primary conduit through which the human body transmits oxygen, nutrients, and other biological information to its peripheral tissues. It does this through bidirectional communication between the blood, consisting of plasma and non-adherent cells, and the microvascular endothelium. Current understanding of this blood–endothelium interface has been predominantly derived from a combination of reductionist two-dimensional in vitro models and biologically complex in vivo animal models, both of which recapitulate the human microvasculature to varying but limited degrees. In an effort to address these limitations, vascularized microfluidics have become a platform of increasing importance as a consequence of their ability to isolate biologically complex phenomena while also recapitulating biochemical and biophysical behaviors known to be important to the function of the blood–endothelium interface. In this review, we discuss the basic principles of vascularized microfluidic fabrication, the contribution this platform has made to our understanding of the blood–endothelium interface in both homeostasis and disease, the limitations and challenges of these vascularized microfluidics for studying this interface, and how these inform future directions. Full article
(This article belongs to the Special Issue Blood-on-a-Chip)
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17 pages, 1339 KiB  
Review
Whole Blood Based Multiparameter Assessment of Thrombus Formation in Standard Microfluidic Devices to Proxy In Vivo Haemostasis and Thrombosis
by Isabella Provenzale, Sanne L. N. Brouns, Paola E. J. van der Meijden, Frauke Swieringa and Johan W. M. Heemskerk
Micromachines 2019, 10(11), 787; https://doi.org/10.3390/mi10110787 - 16 Nov 2019
Cited by 18 | Viewed by 7755
Abstract
Microfluidic assays are versatile tests which, using only small amounts of blood, enable high throughput analyses of platelet function in several minutes. In combination with fluorescence microscopy, these flow tests allow real-time visualisation of platelet activation with the possibility of examining combinatorial effects [...] Read more.
Microfluidic assays are versatile tests which, using only small amounts of blood, enable high throughput analyses of platelet function in several minutes. In combination with fluorescence microscopy, these flow tests allow real-time visualisation of platelet activation with the possibility of examining combinatorial effects of wall shear rate, coagulation and modulation by endothelial cells. In particular, the ability to use blood and blood cells from healthy subjects or patients makes this technology promising, both for research and (pre)clinical diagnostic purposes. In the present review, we describe how microfluidic devices are used to assess the roles of platelets in thrombosis and haemostasis. We place emphasis on technical aspects and on experimental designs that make the concept of “blood-vessel-component-on-a-chip” an attractive, rapidly developing technology for the study of the complex biological processes of blood coagulability in the presence of flow. Full article
(This article belongs to the Special Issue Blood-on-a-Chip)
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