Monolithic separations and analysis of molecules of biological importance
Bibliographic record
Abstract
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.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".