The strive towards “digitization” of chemistry has recently gathered momentum, associated with the dream of a so-called robo-chemist or self-driving laboratory. A suitable candidate as the automated microchemical processing unit of such a self-driving laboratory is digital microfluidics (DMF). In DMF, micro- to nanoliter-sized droplets can be electrically processed on arrays of insulated and hydrophobic electrodes. Hence, this digital control of discrete droplets eliminates the requirement for external pumps and increases the freedom of fluid handling. DMF is usually operated in a closed chip format, preventing evaporation and contamination. However, this makes chemical analysis of the droplets, which are trapped inside the chip, more difficult. Thus, subsequent analytics are usually carried out offline or with simple optical methods.
In recent work, we developed an approach that allows on-the-fly mass spectrometric monitoring of chemical reactions in a DMF device, enabled by a chip-integrated microspray hole (μSH) [1]. This technique uses an electrostatic spray ionization method to spray a portion of a sample droplet through a microhole, allowing its chemical content to be analyzed by mass spectrometry (MS). The broad applicability of the developed seamless coupling of DMF and MS was successfully applied to the study of various on-chip organic syntheses, enzymatic reactions as well as protein and peptide analysis.
While we could successfully combine on-chip MS-detection and DMF, we also extended the scope of our DMF- microspray hole approach for label-free Raman detection [2]. This was made possible by a similar microspray hole that uses an electrostatic spray (ESTAS) for sample transfer from inside the chip to an external insulated SERS substrate. For this purpose, a new ESTAS-compatible stationary SERS substrate was developed and characterized for sensitive and reproducible SERS-based measurements and was successfully applied to study an organic reaction occurring in the DMF device, providing vibrational spectroscopic data.
These approaches offers exciting prospects for transforming digital microfluidics into an automated synthesis platforms by enabling continuous and nearly unlimited tracking of on-chip multi-step chemical processes.
Literature:
[1] A. Das, C. Weise, M. Polack, R. D. Urban, B. Krafft, S. Hasan, H. Westphal, R. Warias, S. Schmidt, T. Gulder, D. Belder, J. Am. Chem. Soc. 2022, 144, 23, 10353–10360. [2] A. Das, S. Fehse, M. Polack, R. Panneerselvam, D. Belder, Anal. Chem. 2023, 95, 1262-1272.