| 1. |
- Novak, R., et al.
(författare)
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Robotic fluidic coupling and interrogation of multiple vascularized organ chips
- 2020
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Ingår i: Nature Biomedical Engineering. - : Nature Research. - 2157-846X.
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Tidskriftsartikel (refereegranskat)abstract
- Organ chips can recapitulate organ-level (patho)physiology, yet pharmacokinetic and pharmacodynamic analyses require multi-organ systems linked by vascular perfusion. Here, we describe an ‘interrogator’ that employs liquid-handling robotics, custom software and an integrated mobile microscope for the automated culture, perfusion, medium addition, fluidic linking, sample collection and in situ microscopy imaging of up to ten organ chips inside a standard tissue-culture incubator. The robotic interrogator maintained the viability and organ-specific functions of eight vascularized, two-channel organ chips (intestine, liver, kidney, heart, lung, skin, blood–brain barrier and brain) for 3 weeks in culture when intermittently fluidically coupled via a common blood substitute through their reservoirs of medium and endothelium-lined vascular channels. We used the robotic interrogator and a physiological multicompartmental reduced-order model of the experimental system to quantitatively predict the distribution of an inulin tracer perfused through the multi-organ human-body-on-chips. The automated culture system enables the imaging of cells in the organ chips and the repeated sampling of both the vascular and interstitial compartments without compromising fluidic coupling.
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| 2. |
- Herland, Anna, et al.
(författare)
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Quantitative prediction of human pharmacokinetic responses to drugs via fluidically coupled vascularized organ chips
- 2020
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Ingår i: Nature Biomedical Engineering. - : Springer Science and Business Media LLC. - 2157-846X. ; 4:4, s. 421-436
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Tidskriftsartikel (refereegranskat)abstract
- Analyses of drug pharmacokinetics (PKs) and pharmacodynamics (PDs) performed in animals are often not predictive of drug PKs and PDs in humans, and in vitro PK and PD modelling does not provide quantitative PK parameters. Here, we show that physiological PK modelling of first-pass drug absorption, metabolism and excretion in humans—using computationally scaled data from multiple fluidically linked two-channel organ chips—predicts PK parameters for orally administered nicotine (using gut, liver and kidney chips) and for intravenously injected cisplatin (using coupled bone marrow, liver and kidney chips). The chips are linked through sequential robotic liquid transfers of a common blood substitute by their endothelium-lined channels (as reported by Novak et al. in an associated Article) and share an arteriovenous fluid-mixing reservoir. We also show that predictions of cisplatin PDs match previously reported patient data. The quantitative in-vitro-to-in-vivo translation of PK and PD parameters and the prediction of drug absorption, distribution, metabolism, excretion and toxicity through fluidically coupled organ chips may improve the design of drug-administration regimens for phase-I clinical trials.
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| 3. |
- Hirao, Yuki, et al.
(författare)
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OGLE-2017-BLG-0406 : Spitzer Microlens Parallax Reveals Saturn-mass Planet Orbiting M-dwarf Host in the Inner Galactic Disk
- 2020
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Ingår i: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 160:2
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery and analysis of the planetary microlensing event OGLE-2017-BLG-0406, which was observed both from the ground and by the Spitzer satellite in a solar orbit. At high magnification, the anomaly in the light curve was densely observed by ground-based-survey and follow-up groups, and it was found to be explained by a planetary lens with a planet/host mass ratio of q = 7.0 x 10(-4) from the light-curve modeling. The ground-only and Spitzer-only data each provide very strong one-dimensional (1D) constraints on the 2D microlens parallax vector pi(E). When combined, these yield a precise measurement of pi(E) and of the masses of the host M-host = 0.56 +/- 0.07 M-circle dot and planet M-planet = 0.41 +/- 0.05 M-Jup. The system lies at a distance D-L = 5.2 +/- 0.5 kpc from the Sun toward the Galactic bulge, and the host is more likely to be a disk population star according to the kinematics of the lens. The projected separation of the planet from the host is a(perpendicular to) = 3.5 +/- 0.3 au (i.e., just over twice the snow line). The Galactic-disk kinematics are established in part from a precise measurement of the source proper motion based on OGLE-IV data. By contrast, the Gaia proper-motion measurement of the source suffers from a catastrophic 10 sigma error.
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