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- Gordon, Laurie J, et al.
(författare)
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Direct Measurement of Intracellular Compound Concentration by RapidFire Mass Spectrometry Offers Insights into Cell Permeability
- 2016
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Ingår i: Journal of Biomolecular Screening. - : Elsevier BV. - 1087-0571 .- 1552-454X. ; 21:2, s. 156-164
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Tidskriftsartikel (refereegranskat)abstract
- One of the key challenges facing early stage drug discovery is understanding the commonly observed difference between the activity of compounds in biochemical assays and cellular assays. Traditionally, indirect or estimated cell permeability measurements such as estimations from logP or artificial membrane permeability are used to explain the differences. The missing link is a direct measurement of intracellular compound concentration in whole cells. This can, in some circumstances, be estimated from the cellular activity, but this may also be problematic if cellular activity is weak or absent. Advances in sensitivity and throughput of analytical techniques have enabled us to develop a high-throughput assay for the measurement of intracellular compound concentration for routine use to support lead optimization. The assay uses a RapidFire-MS based readout of compound concentration in HeLa cells following incubation of cells with test compound. The initial assay validation was performed by ultra-high performance liquid chromatography tandem mass spectrometry, and the assay was subsequently transferred to RapidFire tandem mass spectrometry. Further miniaturization and optimization were performed to streamline the process, increase sample throughput, and reduce cycle time. This optimization has delivered a semi-automated platform with the potential of production scale compound profiling up to 100 compounds per day.
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| 2. |
- Hu, Yuyang, et al.
(författare)
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A Generalized Transition Matrix Model Combined with Discontinuous Galerkin Method for Open Cavities,Generalized transition matrix (GTM), discontinuous Galerkin (DG), open cavity, reference surface
- 2020
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Ingår i: IEEE Open Journal of Antennas and Propagation. - 2637-6431. ; 1:1, s. 272-282
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Tidskriftsartikel (refereegranskat)abstract
- A generalized transition matrix (GTM) model combined with discontinuous Galerkin (DG) method is proposed to analyze the scattering problems of open-ended cavities. A virtual reference surface is put to seal the opening of an open cavity and can separate it into an exterior region and an interior region. By mapping the scattering properties of the internal components onto the reference surface, the information interaction of the GTM model occurs on the reference surface only. With its features of nonconformal meshes at the boundary, the DG method makes the model feasible and accurate regardless of the normal continuity of the surface current at the transitional interface. The GTM model is independent of the exterior structure of the cavity and the external fields. The computational cost can be significantly decreased when the GTM model with the identical inner region is reused. Numerical examples demonstrate good precision and efficiency of the presented method.
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| 3. |
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| 4. |
- Vallin, Örjan, et al.
(författare)
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150 mm Silicon-on-polycrystalline-Silicon Carbide
- 2010
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Ingår i: Proceedings of EUROSOI. ; , s. 101-102
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Konferensbidrag (refereegranskat)abstract
- 150 mm Silicon-on-polycrystallin-Silicon Carbie (poly-SiC) bybrid substrate, without intermediate oxide layers have been realised by hydrophilic wafer bonding of SOI- and poly-SiC wafers. A novel rapid thermal treatment step was introduced before furnace annealing to avoid bubble formation, cracks and breakage. After removal of the Si handle and the buried oxide, the reamining Si device layer was shown to be stress free by Raman spectroscopy and X-ray diffraction (XRD) measurements.
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