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  • 1.
    Acevedo, Juan Pablo
    et al.
    Univ Los Andes, Chile; Cells Cells, Chile.
    Angelopoulos, Ioannis
    Univ Los Andes, Chile; Cells Cells, Chile.
    van Noort, Danny
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, Faculty of Science & Engineering. Univ Los Andes, Chile.
    Khoury, Maroun
    Univ Los Andes, Chile; Cells Cells, Chile; Consorcio Regenero, Chile.
    Microtechnology applied to stem cells research and development2018In: Regenerative Medicine, ISSN 1746-0751, E-ISSN 1746-076X, Vol. 13, no 2, p. 233-248Article, review/survey (Refereed)
    Abstract [en]

    Microfabrication and microfluidics contribute to the research of cellular functions of cells and their interaction with their environment. Previously, it has been shown that microfluidics can contribute to the isolation, selection, characterization and migration of cells. This review aims to provide stem cell researchers with a toolkit of microtechnology (mT) instruments for elucidating complex stem cells functions which are challenging to decipher with traditional assays and animal models. These microdevices are able to investigate about the differentiation and niche interaction, stem cells transcriptomics, therapeutic functions and the capture of their secreted microvesicles. In conclusion, microtechnology will allow a more realistic assessment of stem cells properties, driving and accelerating the translation of regenerative medicine approaches to the clinic.

  • 2.
    Christoffersson, Jonas
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, Faculty of Science & Engineering.
    van Noort, Danny
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, Faculty of Science & Engineering.
    Mandenius, Carl-Fredrik
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, Faculty of Science & Engineering.
    Developing organ-on-a-chip concepts using bio-mechatronic design methodology2017In: Biofabrication, ISSN 1758-5082, E-ISSN 1758-5090, Vol. 9, no 2, article id 025023Article in journal (Refereed)
    Abstract [en]

    Mechatronic design is an engineering methodology for conceiving, configuring and optimising the design of a technical device or product to the needs and requirements of the final user. In this article, we show how the basic principles of this methodology can be exploited for in vitro cell cultures-often referred to as organ-on-a-chip devices. Due to the key role of the biological cells, we have introduced the term bio-mechatronic design, to highlight the complexity of designing a system that should integrate biology, mechanics and electronics in the same device structure. The strength of the mechatronic design is to match the needs of the potential users to a systematic evaluation of overall functional design alternative. It may be especially attractive for organs-on-chips where biological constituents such as cells and tissues in 3D settings and in a fluidic environment should be compared, screened and selected. Through this approach, design solutions ranked to customer needs are generated according to specified criteria, thereby defining the key constraints of the fabrication. As an example, the bio-mechatronic methodology is applied to a liver-on-a-chip based on information extrapolated from previous theoretical and experimental knowledge. It is concluded that the methodology can generate new fabrication solutions for devices, as well as efficient guidelines for refining the design and fabrication of many of todays organ-on-a-chip devices.

  • 3.
    Kim, Taehoon H.
    et al.
    DGIST, South Korea.
    Hahn, Young Ki
    Samsung Elect, South Korea.
    Lee, Jungmin
    DGIST, South Korea.
    van Noort, Danny
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, Faculty of Science & Engineering. DGIST, South Korea.
    Kim, Minseok S.
    DGIST, South Korea.
    Solenoid Driven Pressure Valve System: Toward Versatile Fluidic Control in Paper Microfluidics2018In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 90, no 4, p. 2534-2541Article in journal (Refereed)
    Abstract [en]

    As paper-based diagnostics has become predominantly driven by more advanced microfluidic technology, many of the research efforts are still focused on developing reliable and versatile fluidic control devices, apart from improving sensitivity and reproducibility. In this work, we introduce a novel and robust paper fluidic control system enabling versatile fluidic control. The system comprises a linear push-pull solenoid and an Arduino Uno micro controller. The precisely controlled pressure exerted on the paper stops the flow. We first determined the stroke distance of the solenoid to obtain a constant pressure while examining the fluidic time delay as a function of the pressure. Results showed that strips of grade 1 chromatography paper had superior reproducibility in fluid transport. Next, we characterized the reproducibility of the fluidic velocity which depends on the type and grade of paper used. As such, we were able to control the flow velocity on the paper and also achieve a complete stop of flow with a pressure over 2.0 MPa. Notably, after the actuation of the pressure driven valve (PDV), the previously pressed area regained its original flow properties. This means that, even on a previously pressed area, multiple valve operations can be successfully conducted. To the best of our knowledge, this is the first demonstration of an active and repetitive valve operation in paper microfluidics. As a proof of concept, we have chosen to perform a multistep detection system in the form of an enzyme-linked immunosorbent assay with mouse IgG as the target analyte.

  • 4.
    Nguyen, Dao Thi Thuy
    et al.
    Ewha Womans Univ, Dept Chem & Nano Sci, Seoul 03760, South Korea.
    van Noort, Danny
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, Faculty of Science & Engineering.
    Jeong, In-Kyung
    Kyung Hee University, South Korea.
    Park, Sungsu
    Sungkyunkwan University, South Korea.
    Endocrine system on chip for a diabetes treatment model2017In: Biofabrication, ISSN 1758-5082, E-ISSN 1758-5090, Vol. 9, no 1, article id 015021Article in journal (Refereed)
    Abstract [en]

    The endocrine system is a collection of glands producing hormones which, among others, regulates metabolism, growth and development. One important group of endocrine diseases is diabetes, which is caused by a deficiency or diminished effectiveness of endogenous insulin. By using a microfluidic perfused 3D cell-culture chip, we developed an endocrine system on chip to potentially be able to screen drugs for the treatment of diabetes by measuring insulin release over time. Insulin-secreting beta-cells are located in the pancreas, while L-cells, located in the small intestines, stimulate insulin secretion. Thus, we constructed a co-culture of intestinal-pancreatic cells to measure the effect of glucose on the production of glucagon-like peptide-1 (GLP-1) from the L-cell line (GLUTag) and insulin from the pancreatic beta-cell line (INS-1). After three days of culture, both cell lines formed aggregates, exhibited 3D cell morphology, and showed good viability (amp;gt; 95%). We separately measured the dynamic profile of GLP-1 and insulin release at glucose concentrations of 0.5 and 20 mM, as well as the combined effect of GLP-1 on insulin production at these glucose concentrations. In response to glucose stimuli, GLUTag and INS-1 cells produced higher amounts of GLP-1 and insulin, respectively, compared to a static 2D cell culture. INS-1 combined with GLUTag cells exhibited an even higher insulin production in response to glucose stimulation. At higher glucose concentrations, the diabetes model on chip showed faster saturation of the insulin level. Our results suggest that the endocrine system developed in this study is a useful tool for observing dynamical changes in endocrine hormones (GLP-1 and insulin) in a glucose-dependent environment. Moreover, it can potentially be used to screen GLP-1 analogues and natural insulin and GLP-1 stimulants for diabetes treatment.

  • 5.
    Pasitka, Laura
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, Faculty of Science & Engineering.
    van Noort, Danny
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, Faculty of Science & Engineering.
    Lim, Wanyoung
    Sungkyunkwan Univ, South Korea.
    Park, Sungsu
    Sungkyunkwan Univ, South Korea.
    Mandenius, Carl-Fredrik
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, Faculty of Science & Engineering.
    A Microbore Tubing Based Spiral for Multistep Cell Fractionation2018In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 90, no 21, p. 12909-12916Article in journal (Refereed)
    Abstract [en]

    Cells were separated with the aid of a multistep spiral fractionation device, utilizing hydrodynamic forces in a spiral tubing. The spiral was fabricated using "off-the-shelf microbore tubing, allowing for cheap and fast prototyping to achieve optimal cell separation. As a first step, a model system with 20 and 40 mu m beads was used to demonstrate the effectiveness of the multistep separation device. With an initial purity of 5%, a separation purity of 83% was achieved after a two-step separation with the addition of 0.1% polyethylene glycol (PEG)-8000. Next, doxorubicinresistant polyploid giant breast cancer cells (MDA-MB-231) were separated from doxorubicin-sensitive monoploid small breast cancer cells in the same fashion as the beads, resulting in a purity of around 40%, while maintaining a cell viability of more than 90%. Combined with basic cell analytical methods, the hydrodynamic separation principle of the device could be envisaged to be useful for a variety of cell fractionation needs in cell biology and in clinical applications.

  • 6.
    Toh, Yi-Chin
    et al.
    Department of Biomedical Engineering, 4 Engineering Drive, National University of Singapore, Singapore 117853, Singapore. biety@nus.edu.sg; Institute of Bioengineering and Nanotechnology, A*STAR, The Nanos, #04-01, 31 Biopolis Way, Singapore 138669, Singapore.
    Raja, Anju
    Institute of Bioengineering and Nanotechnology, A*STAR, The Nanos, #04-01, 31 Biopolis Way, Singapore 138669, Singapore. anju.mythreyi.raja@ihis.com.sg; Integrated Health Information Systems (IHiS), 6 Serangoon North Avenue 5, Singapore 554910, Singapore.
    Yu, Hanry
    Institute of Bioengineering and Nanotechnology, A*STAR, The Nanos, #04-01, 31 Biopolis Way, Singapore 138669, Singapore. medyuh@nus.edu.sg; Department of Physiology, Yong Loo Lin School of Medicine, MD9-04-11, 2 Medical Drive, Singapore 117597, Singapore. medyuh@nus.edu.sg; Mechanobiology Institute, National University of Singapore, T-Lab, #05-01, 5A Engineering Drive 1, Singapore 117411, Singapore. medyuh@nus.edu.sg; Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, #10-01 CREATE Tower, Singapore 138602, Singapore. medyuh@nus.edu.sg; NUS Graduate Programme in Bioengineering, NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 117597, Singapore. medyuh@nus.edu.sg; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. medyuh@nus.edu.sg; Gastroenterology Department, Southern Medical University, Guangzhou 510515, China.
    van Noort, Danny
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, Faculty of Science & Engineering. Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Korea.
    A 3D Microfluidic Model to Recapitulate Cancer Cell Migration and Invasion2018In: Bioengineering (Basel, Switzerland), ISSN 2306-5354, Vol. 5, no 2Article in journal (Refereed)
    Abstract [en]

    We have developed a microfluidic-based culture chip to simulate cancer cell migration and invasion across the basement membrane. In this microfluidic chip, a 3D microenvironment is engineered to culture metastatic breast cancer cells (MX1) in a 3D tumor model. A chemo-attractant was incorporated to stimulate motility across the membrane. We validated the usefulness of the chip by tracking the motilities of the cancer cells in the system, showing them to be migrating or invading (akin to metastasis). It is shown that our system can monitor cell migration in real time, as compare to Boyden chambers, for example. Thus, the chip will be of interest to the drug-screening community as it can potentially be used to monitor the behavior of cancer cell motility, and, therefore, metastasis, in the presence of anti-cancer drugs.

  • 7.
    van Noort, Danny
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, Faculty of Science & Engineering.
    Editorial for the Special Issue on Microfluidics for Cells and Other Organisms2019In: Micromachines, ISSN 2072-666X, E-ISSN 2072-666X, MICROMACHINES, ISSN 2072-666X, Vol. 10, no 8, article id 520Article in journal (Other academic)
    Abstract [en]

    n/a

1 - 7 of 7
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