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      Multiscale Biofluidic and Nanobiotechnology Approaches for Treating Sepsis in Extracorporeal Circuits

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          Abstract

          Infectious diseases and their pandemics periodically attract public interests due to difficulty in treating the patients and the consequent high mortality. Sepsis caused by an imbalanced systemic inflammatory response to infection often leads to organ failure and death. The current therapeutic intervention mainly includes “the sepsis bundles,” antibiotics (antibacterial, antiviral, and antifungal), intravenous fluids for resuscitation, and surgery, which have significantly improved the clinical outcomes in past decades; however, the patients with fulminant sepsis are still in desperate need of alternative therapeutic approaches. One of the potential supportive therapies, extracorporeal blood treatment, has emerged and been developed for improving the current therapeutic efficacy. Here, I overview how the treatment of infectious diseases has been assisted with the extracorporeal adjuvant therapy and the potential utility of various nanobiotechnology and microfluidic approaches for developing new auxiliary therapeutic methods.

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          Most cited references39

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          An extracorporeal blood-cleansing device for sepsis therapy.

          Here we describe a blood-cleansing device for sepsis therapy inspired by the spleen, which can continuously remove pathogens and toxins from blood without first identifying the infectious agent. Blood flowing from an infected individual is mixed with magnetic nanobeads coated with an engineered human opsonin--mannose-binding lectin (MBL)--that captures a broad range of pathogens and toxins without activating complement factors or coagulation. Magnets pull the opsonin-bound pathogens and toxins from the blood; the cleansed blood is then returned back to the individual. The biospleen efficiently removes multiple Gram-negative and Gram-positive bacteria, fungi and endotoxins from whole human blood flowing through a single biospleen unit at up to 1.25 liters per h in vitro. In rats infected with Staphylococcus aureus or Escherichia coli, the biospleen cleared >90% of bacteria from blood, reduced pathogen and immune cell infiltration in multiple organs and decreased inflammatory cytokine levels. In a model of endotoxemic shock, the biospleen increased survival rates after a 5-h treatment.
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            Combined microfluidic-micromagnetic separation of living cells in continuous flow.

            This paper describes a miniaturized, integrated, microfluidic device that can pull molecules and living cells bound to magnetic particles from one laminar flow path to another by applying a local magnetic field gradient, and thus selectively remove them from flowing biological fluids without any wash steps. To accomplish this, a microfabricated high-gradient magnetic field concentrator (HGMC) was integrated at one side of a microfluidic channel with two inlets and outlets. When magnetic micro- or nano-particles were introduced into one flow path, they remained limited to that flow stream. In contrast, when the HGMC was magnetized, the magnetic beads were efficiently pulled from the initial flow path into the collection stream, thereby cleansing the original fluid. Using this microdevice, living E. coli bacteria bound to magnetic nanoparticles were efficiently removed from flowing solutions containing densities of red blood cells similar to that found in blood. Because this microdevice allows large numbers of beads and cells to be sorted simultaneously, has no capacity limit, and does not lose separation efficiency as particles are removed, it may be especially useful for separations from blood or other clinical samples. This on-chip HGMC-microfluidic separator technology may potentially allow cell separations to be carried out in the field outside of hospitals and clinical laboratories.
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              Rapid Diagnosis of Ebola Hemorrhagic Fever by Reverse Transcription-PCR in an Outbreak Setting and Assessment of Patient Viral Load as a Predictor of Outcome

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                Author and article information

                Contributors
                jookang@unist.ac.kr
                Journal
                Biochip J
                Biochip J
                Biochip Journal
                The Korean BioChip Society (KBCS) (Seoul )
                1976-0280
                2092-7843
                12 March 2020
                : 1-9
                Affiliations
                GRID grid.42687.3f, ISNI 0000 0004 0381 814X, Department of Biomedical Engineering, , Ulsan National Institute of Science and Technology (UNIST), ; 50, UNIST-gil, Ulsan, 44919 Republic of Korea
                Author information
                https://orcid.org/0000-0001-9636-3209
                Article
                4106
                10.1007/s13206-020-4106-6
                7095347
                32218896
                f9992a1a-c971-4acd-b4c0-eed115538c07
                © The Korean BioChip Society and Springer 2020

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 12 February 2020
                : 1 March 2020
                Categories
                Review Article

                microfluidics,nanobiotechnology,extracorporeal devices,infectious diseases,blood treatment,sepsis

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