The effect of sample composition acoustic droplet ejection of small molecules in DMSO

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dc.contributor.authorLadisic, Sebastian
dc.contributor.departmentChalmers tekniska högskola / Institutionen för kemi och kemitekniksv
dc.contributor.departmentChalmers University of Technology / Department of Chemistry and Chemical Engineeringen
dc.contributor.examinerLarsson, Anette
dc.contributor.supervisorSvensson, Martin
dc.date.accessioned2023-07-04T12:42:22Z
dc.date.available2023-07-04T12:42:22Z
dc.date.issued2023
dc.date.submitted2023
dc.description.abstractAstraZeneca is pioneering within life science research and development, and contributes significantly in reducing the numbers of deaths caused by non-communicable diseases. Laboratory automation has contributed to the heavily increased number of screening assays in modern times and AstraZeneca has teamed up with Brooks Life Sciences, Beckman Coulter Life Sciences and Titian, to create a workflow that uses acoustic droplet ejection for transferring low volumes of liquid samples in an efficient and risk free process. Samples that pose problems in the liquid handler are removed from the chemical library and thus slow down the drug discovery and development process. This study evaluates any correlation between failure in acoustic dispensing and the sample composition of 50 suspensions of different small molecules in dimethyl sulfoxide. The samples are characterized by their solid particle shape, size and crystallinity, and a liquid chromatography - mass spectrometry method is developed to determine if the precipitate represents the original compound. Five sizes of poly(methyl metacrylate) microspheres are used in model suspensions for evaluating the interaction between solid particles and the acoustic signals. The results show that no suspension is contaminated and that the acoustic dispensing is not dependent on size, shape or crystallinity of the precipitate particles. The dispensing failure probably occurs from a combination of reflection and scattering of the acoustic signal that measures the sample volume in the tubes, and seems to be dependent on the amount of solid particles and their position on the tube bottom. This study concludes that the bare presence of solid particles is enough to make a sample incompatible with acoustic dispensing, and a reasonable solution is to implement a separate workflow for compounds that are poorly soluble in the solvent of choice. An alternative workflow is presented in the final section of the report.
dc.identifier.coursecodeKBTX12
dc.identifier.urihttp://hdl.handle.net/20.500.12380/306571
dc.language.isoeng
dc.setspec.uppsokPhysicsChemistryMaths
dc.subjectAcoustic dispensing
dc.subjectSample characterization
dc.subjectSolubility
dc.subjectLiquid chromatography
dc.subjectMass spectrometry
dc.titleThe effect of sample composition acoustic droplet ejection of small molecules in DMSO
dc.type.degreeExamensarbete för masterexamensv
dc.type.degreeMaster's Thesisen
dc.type.uppsokH
local.programmeMaterials chemistry (MPMCN), MSc
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