The effect of sample composition acoustic droplet ejection of small molecules in DMSO
Typ
Examensarbete för masterexamen
Master's Thesis
Master's Thesis
Program
Materials chemistry (MPMCN), MSc
Publicerad
2023
Författare
Ladisic, Sebastian
Modellbyggare
Tidskriftstitel
ISSN
Volymtitel
Utgivare
Sammanfattning
AstraZeneca 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.
Beskrivning
Ämne/nyckelord
Acoustic dispensing , Sample characterization , Solubility , Liquid chromatography , Mass spectrometry