High-Throughput Microbore LC-MS Lipidomics to Investigate APOE Phenotypes
| Authors | |
|---|---|
| Year of publication | 2024 |
| Type | Article in Periodical |
| Magazine / Source | Analytical chemistry |
| MU Faculty or unit | |
| Citation | |
| Web | https://pubs.acs.org/doi/10.1021/acs.analchem.3c02652 |
| Doi | http://dx.doi.org/10.1021/acs.analchem.3c02652 |
| Keywords | CHROMATOGRAPHY-MASS SPECTROMETRY; ALZHEIMERS-DISEASE; CHOLESTEROL; SYSTEMS |
| Attached files | |
| Description | Microflow liquid chromatography interfaced with mass spectrometry (mu LC-MS/MS) is increasingly applied for high-throughput profiling of biological samples and has been proven to have an acceptable trade-off between sensitivity and reproducibility. However, lipidomics applications are scarce. We optimized a mu LC-MS/MS system utilizing a 1 mm inner diameter x 100 mm column coupled to a triple quadrupole mass spectrometer to establish a sensitive, high-throughput, and robust single-shot lipidomics workflow. Compared to conventional lipidomics methods, we achieve a similar to 4-fold increase in response, facilitating quantification of 351 lipid species from a single iPSC-derived cerebral organoid during a 15 min LC-MS analysis. Consecutively, we injected 303 samples over similar to 75 h to prove the robustness and reproducibility of the microflow separation. As a proof of concept, mu LC-MS/MS analysis of Alzheimer's disease patient-derived iPSC cerebral organoid reveals differential lipid metabolism depending on APOE phenotype (E3/3 vs E4/4). Microflow separation proves to be an environmentally friendly and cost-effective method as it reduces the consumption of harmful solvents. Also, the data demonstrate robust, in-depth, high-throughput performance to enable routine clinical or biomedical applications. |
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