Novel Ionization Source for Microfluidic Mass Spectrometry Interfacing

Leslie Yeo & James Friend, Micro/Nanophysics Research Lab, Monash University, Australia; David Go, Aerospace & Mechanical Engineering & Hsueh-Chia Chang, Chemical & Biomolecular Engineering, University of Notre Dame

A PDF version is available in the Fall 2011 AES Newsletter.

Coupled with separation techniques such as high performance liquid chromatography (HPLC), mass spectrometry remains among the most widely used tools for chemical and biochemical analysis due to its superior speed, sensitivity, and specificity. With the emergence of efficient sample preparation using microfluidic devices, there is growing interest in interfacing microfluidic devices with mass spectrometers (MS) to allow seamless in-line analysis within an integrated platform [1]. An example of such interfacing is the Agilent Nano LC/MS, which integrates an HPLC chip with MS. As the development of miniaturized MS units progresses, portable uses for forensics and homeland security as well as environmental and therapeutic drug monitoring become a real possibility.

Figure 1 Schematic depiction of the SAW-MS interface. The SAW is generated by applying an input RF signal to the interdigitated electrodes pat- terned onto the device. The analyte solution, delivered to the SAW substrate through a paper wick, is rapidly atomized when in contact with the SAW propagating on the substrate surface. The atomized droplets comprising the target analyte possess an inherent charge and are directed to the MS inlet for detection.

The MS operating principle, wherein gas phase analyte ions are separated based on their mass to charge ratio, necessitates the incorporation of an ionization source. With increasing use of MS for proteomic analysis, soft-ionization methods in which fragmentation of the analyte molecules is minimized are often desirable. The most popular soft ionization methods currently in use are electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI). Nevertheless, these methods are often associated with various setbacks such as spray stability and signal suppression due to matrix ions. There are also practical limitations on their use; for example, ESI is usually limited to polar compounds with large molecular mass. Moreover, the large voltage associated with ESI and the necessity for a laser in MALDI render miniaturization of these ionization sources onto a microfluidic chip interface a challenge.

Recently, a new chip-scale ionization source based on surface acoustic wave (SAW) atomization has been demonstrated as a microfluidic-MS interface (Fig. 1) [2,3]. SAWs are nanometer amplitude Rayleigh waves that propagate along the surface of a piezoelectric substrate at MHz frequencies and above. In the last decade, SAWs have emerged as a powerful tool for microscale and nanoscale fluid actuation and bioparticle manipulation [4,5]. Above a critical power, typically around 1 to 4 W, one to two orders of magnitude smaller than that usually required with ultrasonic atomizers, it is possible with the SAW to sufficiently destabilize the interface of a sessile liquid drop placed atop the substrate such that it subsequently breaks up to form a mist of aerosol droplets around 1 to 10 microns in diameter [6].

Given that the SAW is essentially an electroelastic wave, the atomized droplets possess an inherent charge, typically about 100-300 nC [3]. While this can be smaller than the charge on electrospray droplets, the total charge and current appear to be sufficient to use the SAW atomization process as an ionization source for mass spectrometry [3]. The external pulsed corona source between the SAW device and the MS inlet used in earlier work [2] is not required; the SAW atomization device can exist as a standalone MS ionization source. Further, it was shown that the paper-based wick used to deliver the analyte sample from the reservoir to the SAW device has the capability of filtering sample contaminants, thus allowing low-cost, disposable analysis without the necessity for sample pretreatment or separation [3,7].

  1. S Freire, AR Wheeler. Interfaces Between Microfluidics and Mass Spectrometry. in Encyclopedia of Microfluidics and Nanofluidics (ed. D Li), pp. 849-854 (Springer, New York, 2008).
  2. SR Heron, R Wilson, SA Shaffer, DR Goodlett, JM Cooper. Surface Acoustic Wave Nebulization of Peptides As a Microfluidic Interface for Mass Spectrometry. Anal Chem 82, 3985 (2010).
  3. J Ho, MK Tan, DB Go, LY Yeo, JR Friend, H-C Chang. Paper-Based Microfluidic Surface Acoustic Wave Sample Delivery and Ionization Source for MS. Anal Chem 83, 3250 (2011).
  4. LY Yeo, JR Friend. Ultrafast Microfluidics Using Surface Acoustic Waves. Biomicrofluidics 3, 012002 (2009).
  5. J Friend, LY Yeo. Microscale Acoustofluidics: Rev Mod Phys 83, 647 (2011).
  6. A Qi, LY Yeo, JR Friend. Interfacial Destab. and Atomization Driven by Surface Acoustic Waves. Phys Fluids 20, 074103 (2008). 7. A Qi, L Yeo, J Friend, J Ho. The Extraction of Liquid, Protein Molecules and Yeast Cells from Paper Through Surface Acoustic Wave Atomization. Lab Chip 10, 470 (2010).