Monolithic separations and analysis of molecules of biological importance
Notice bibliographique
Résumé
Monolithic stationary phases are attractive tools for chromatographic separations and analyte extraction from complex matrices. Monoliths with porous surfaces can be cast as thin films or with flow channels for monolithic chromatographic columns. Monoliths describe a wide variety of materials, either organic or inorganic in nature, and in several physical forms. Methacrylate-co-ethylene glycol dimethacrylate polymers are especially of importance for separations of biomolecules. These polymers exhibit high biocompatibility and are highly tunable to isolate compounds ranging from small molecules to large molecular weight species, with a wide range or polarities. One way to achieve additional selectivity in these polymers is the introduction of molecular imprinting through the addition of a template molecule during casting. The template is removed after curing, leaving a cavity with high selectivity toward the analytes of interest. In this thesis, both molecularly imprinted and non-imprinted monoliths are employed for isolation and analysis of molecules of importance from complex biological matrices. Mycophenolic acid (MPA) is an anti-rejection drug commonly administered after organ transplant. The interpatient variability of free MPA in blood is very high, due to complex pharmacokinetic and pharmacokinetic properties of the molecule and must be closely monitored during and after therapeutic drug administration. A monolithic thin film molecularly imprinted polymer (TF-MIP) was developed to selectively extract MPA from human plasma in a simple and rapid process. Tyrosine kinase inhibitors (TKIs) are a class of compounds which are commonly used as chemotherapeutic agents for cancer patients. A TF-MIP was designed for the extraction of representative TKIs (imatinib, dasatinib, ponatinib, and nilotinib) in human plasma in a 96-well plate format. The developed extraction regime allowed for highthroughput sample processing with a minimum amount of sample handling using small volumes of plasma. Gene transfer agents (GTAs) are virus-like particles that transport genetic material from one bacterium to another. Using a 2-step monolithic chromatographic approach, a new method for the preparative isolation of functional GTAs from Rhodobacter capsulatus was developed. The isolated particles were intact after isolation and could transfer genetic material. The newly developed process allows for purification and concentration of the particles for downstream use in biochemical, bacterial, and genetic assays, allowing for the advancement of knowledge about GTAs and the discovery of previously undiscovered GTAs. The method also has broad applicability to many small phages which are the focus of phage therapies that are used to fight antibiotic resistant bacterial infections in humans. Coated-blade spray (CBS) mass spectrometry is a technique for direct sample introduction without traditional chromatographic separation. Innovative CBS workflows allow for rapid and simple analyses of a wide variety of compounds. Compared to traditional workflows, CBS methods are particularly attractive for biological matrices due to simplified sample processing. A custom coated-blade spray source was developed for the Xevo TQ-S where data is presented for measurement of mycophenolic acid, cocaine, MDMA, methamphetamine, methadone and methadone-d3 in human biological fluids. A custom source was designed and used to semi-quantitatively measure mycophenolic acid on the MX908 handheld MS. A fibreglass fabric-based MIP mesh was used with the thermal desorption accessory of the MX908 to measure the organophosphorus pesticides malathion and chlorpyrifos in water.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,001 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,002 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».