New Interfaces and Applications for Digital Microfluidics with In-Line Mass Spectrometry Analysis

Abstract

Mass Spectrometry (MS) is an indispensable tool for laboratory science, but a drawback is the laborious and time-consuming sample preparation that is often required before MS analysis. Microfluidics presents a potential solution to this problem, as it offers the benefits of reduced reagent consumption and processing times, the capacity to integrate multiple functions on a single device, and potential for automated and high-throughput analysis. Digital microfluidics (DMF) is an emerging technology that may be particularly well-equipped for the kinds of sample processing steps required for MS analysis, such as extraction, derivatization, and sample clean-up. DMF is a microscale liquid handling technique characterized by the manipulation of droplets on insulated electrode arrays. Using DMF, droplets can be made to merge, mix, split, and dispense from reservoirs. Since droplets are manipulated individually and act as discrete microreactors, DMF offers total process control. Coupling the versatility of MS analysis with DMF sample handling has been beneficial for a number of DMF-based applications, but is often limited by off-line analysis. The work described in this thesis was designed to address this problem - how to couple DMF to mass spectrometry for in-line analysis. This thesis describes three new interfaces for DMF with in-line MS analysis. First, folded polyimide nanoESI emitters were developed as a low-cost alternative to conventionally used pulled-glass capillary emitters. Folded emitters were integrated with DMF devices on a single flexible substrate to form a device for in-line sample processing and analysis that was used for real-time microscale reaction monitoring. The second interface was a paper-based monolithic device format used to couple DMF with paper spray ionization MS. The third interface was used for a new DMF-based protocol for the extraction and quantification of drugs of abuse from a dried urine matrix using pulled-glass nanoESI MS emitters. This integrated device format was used to couple DMF with a miniature mass spectrometer for portable quantitative analysis. The three complementary interfaces have potential for a wide variety of applications, and could have impact in the fields of microscale chemical synthesis and bioanalysis by providing a robust and facile means for sample processing with in-line analysis by mass spectrometry.