Rahul Narayanan26-09-2015

Introduction• Lab-on-a-chip platforms are attractive tools in modern chemistry with high potential to combine

different processes, such as chemical synthesis and analytical monitoring on a single device.

• This approach opens entirely new possibilities to study chemical processes on small time scales. Minimal resource consumption and vastly accelerated reaction rates of diffusion-limited processes facilitate rapid optimization and investigation of chemical synthesis, for example, screening of catalysts.

• Integration of micro-free-flow electrophoresis (µFFE) into lab-on-a-chip platforms is especially appealing, because it can be combined seamlessly with continuous flow-reactors.

First approach of coupling µFFE with MS directly. An electrospray is generated by a monolithic emitter tip machined into the µFFE borosilicate microchips end.

Free-flow electrophoresis (FFE) is a technique that performs an electrophoretic separation on a continuous stream of analyte as it flows through a planar flow channel. The electric field is applied perpendicularly to the flow to deflect analytes laterally according to their mobility as they flow through the separation channel.

Layout of a microfluidic FFE-MS chip

The analysis principle

Components of the μFFE-MS setup

Microfluidic FFE chip setup in front of Q-TOF-MS

Top view of microchip layout

Instrumen

tation

Monitorin

g of contin

uous

microprpara

tive s

epara

tion

Extracted ion currents of fluorophores obtained by μFFE-MS. Annotated are the time periods used for averaging of mass spectra.

a) Extracted ion currents of protonated molecular ions for the fluorescent dyes as well as fluorescence intensity (in gray) are shown. b) Photograph of the mFFE-MS chip, c) Magnification of make-up intersection. Lengths of arrows are indicating relative flow rates.

Mass spectrum and corresponding fluorescence image

Reaction monitoring

A multicomponent [3+2]-cycloannulation experiment. a) Extracted ion currents of anthranilic acid (1) and specific 1st generation fragments of the reaction products 4 and 5. b) Illustration of obtained fractions.

1. anthranilic acid2. benzaldehyde 3. bis(silyl)dienediolate

4. pyrrolobenzoxazinone

Extracted ion counts for μFFE-MS experiment without fragmentation

1st Generation product ions of m/z 338.1 for both distinct electromigrative species obtained with μFFE-MS. a) fragment spectrum assigned to pyrrolobenzoxazinone 4. b) fragment spectrum and proposed structure of the side product 5 formed by an “a-addition” of nucleophile 2. Most abundant characteristic product ions are underlined.

Summary and conclusions

• The on-chip coupling of free-flow electrophoresis and mass spectrometry presented herein, enables the monitoring of continuous micropreparative separation, which is especially viable for continuous-flow reactors.

• A new tool to realize complex chemical circuits is thereby available, which makes the combination of micro-flow-through synthesis, separation, and analysis possible.

• This new approach has great potential regarding the implementation of multistep synthesis in highly integrated lab-on-a-chip systems.