SUMMARY

In-situ, time resolved monitoring of cell culture environments, e.g., therapeutic cell bioreactors, is of increasing importance as new cell therapies require quality control measures. The Dynamic Mass Spectrometry Probe (DMSP) synergistically incorporates a sampling interface for localized intake, a micro-fabricated mass exchanger for sample treatment, and an electrospray ionization (ESI) outlet for qualitative/quantitative information on key biomolecules related to cell health and efficacy transiently (~1 min). DMSP is enabled by advanced batch microfabrication techniques to minimize dead volume (~20 nL) and ensure repeatable operation & geometry of each device. Sample modification is carried out via mass exchange through a nanoporous membrane. DMSP has demonstrated ability to increase signal to noise ratio of biomolecules with standard desalination, and to further enhance sensitivity at lower concentrations with the simultaneous introduction of supercharging molecules into the sample during desalination within the integrated mass exchanger. Changing the geometry of the sample treatment channel, and changing from parallel flow to cross flow orientation treatment will further improve device effectiveness for direct cell bioreactor monitoring. With direct infusion to MS, online treatment and analysis of samples from near cell membranes within a bioreactor will provide insight transiently of biomarkers key to determining cell health and efficacy. This thesis research will make fundamental contributions to (1) understanding multicomponent mass transfer in micro/nano-scale confinement of MEMS mass exchangers, (2) electrocapillarity-assisted flow of complex mixtures including biomolecules, along with development new hybrid micro/nano-fabrication processes for monolithically integrated lab-on-chip microdevices.