INTERFACING DROPLET MICROFLUIDICS WITH INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY

Pascal E. Verboket, Olga Borovinskaya, Detlef Günther and Petra S. Dittrich* Department of Chemistry and Applied Biosciences, ETH Zurich, SWITZERLAND

ABSTRACT

We present a novel method to interface a continuous-flow droplet-based microfluidic system with inductively coupled plasma mass spectrometry (ICP-MS). Our system has remarkable advantages over existing droplet injection systems for ICP-MS such as the low price, little maintenance and robustness against clogging. In a proof of principle experiment with the novel interface, a 2 mg/kg Uranium nitrite standard solution was injected and successfully measured by ICP-MS. The synergy between droplet microfluidics and ICP-MS simplifies the ultrasensitive elemental analysis of the content of picolitre droplets. KEYWORDS: droplet microfluidics, inductively coupled plasma mass spectrometry, ICP-MS, interface, direct injection

INTRODUCTION

Today, ICP-MS is a highly sensitive analytical method for elemental analysis of single nanoparticles [1] or individual cells labeled with rare-earth isotopes [2]. However, this kind of analysis requires a discrete sample introduction system with 100 % sample transport efficiency. Commercially available droplet injection modules are expensive, suffer from a narrow droplet size range, are prone to clogging and difficult to clean. Therefore, a new, more flexible, robust and low-maintenance sample introduction system is of interest for measurements of nanoparticles and single cells by ICP-MS.

Here, we introduce a novel microfluidic system for droplet generation and direct injection into the ICP mass spectrometer (Figure 1). The core component consists of a downwards-facing liquid assisted droplet ejection (LADE) chip, which is entirely made of PDMS (Figure 2). The round shape of the LADE chip facilitates direct insertion into the socket of the ICP-MS.

Figure 1: Schematic of the droplet ICP-MS interface. In the downwards-facing LADE chip droplets are generated using a highly volatile oil phase. This droplet stream is injected into a cyclonic helium stream. In the following stainless steel tube the falling aqueous droplets and their surrounding oil shell are evaporated, leaving behind only the content of the

aqueous phase. The vapor phase is removed using a membrane desolvator. After the addition of Argon the dried droplets are introduced into the plasma of an ICP-MS.

978-0-9798064-6-9/µTAS 2013/$20©13CBMS-0001 928 17th International Conference on MiniaturizedSystems for Chemistry and Life Sciences27-31 October 2013, Freiburg, Germany

Figure 2: Photograph of the LADE chip, fluid channels are filled with blue food dye for visualization. The chip consists

entirely of PDMS. The round part of the chip can be directly placed into the socket of the ICP-MS transport system, while the other part contains the three access holes for sample and perfluorohexane introduction.

EXPERIMENTAL The LADE chips used throughout the experiments consisted of two halves. One half contained the microfluidic channels with a height of 40 µm and was fabricated using the standard PDMS (Sylgard 184, Dow Corning, US) soft lithography. The silicon masters for this process were fabricated in a clean room using SU-8 2050 (Microchem, US). A custom made casting form ensured that a part of the PDMS forms a half round shape. Holes for supplying the liquids were punched in the structured half using a biopsy puncher. The second half of the chip was prepared in the same manner but contained no microfluidic structures. Both parts were bonded together by transferring a thin spin coated layer of the PDMS curing agent on the structured half. Subsequently, both halves were positioned on top of each other, aligned and cured for 24 h at room temperature. Prior to usage, the top of the chip was cut off to ensure straight liquid ejection. All liquids were supplied using syringe pumps (Cetoni, Germany).

RESULTS AND DISCUSSION

A micrograph of the microfluidic channels in the LADE chip is shown in figure 3. In a first channel junction, monodisperse droplets of an aqueous solution are generated using the highly volatile perfluorohexane as oil phase. A second junction is used to add further perfluorohexane in order to increase the flow velocity and hence, enable ejection of the liquid in a stable jet.

Figure 3: Micrograph of the droplet generation and acceleration. In the first junction aqueous droplets are created and transported to the second junction in the stream of highly volatile perfluorohexane. The subsequent further addition of

perfluorohexane at the second junction results in the acceleration of the droplets to a final speed of 2 m/s, which is nec-essary to eject the droplets from the chip. Scale bar 100 µm.

Test experiments with a high-speed camera proved that the use of two junctions is suitable to control the droplet

generation independent from the acceleration. The liquid jet is injected into a cyclonic helium stream [3]. After ejection, the oil carrier phase breaks into small droplets while the aqueous droplets remain intact inside an oil shell (Figure 4 and 5). In the following falling tube aqueous droplets and their surrounding oil shell are partially evaporated. A residue of an aqueous droplet remains in the tube and is further transported to the ICP-MS. The vapor of the volatile oil phase is removed using a membrane desolvator. After the addition of Argon to improve ionization and transport of the analytes, the desolved residues are introduced into the plasma of the ICP- MS.

Figure 4: Micrograph of the droplet stream exiting the LADE chip through the nozzle (diameter: 25 µm). Arrow indi-

cates the direction of flow. Scale bar 100 µm.

Figure 5: Micrograph of aqueous droplets (small bright dot, volume: 33 pL) and their surrounding oil shell (total

volume: 523 pL) after ejection from the LADE chip. Scale bar 100 µm.

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The interface was used for measurements of a 2 mg/kg Uranium nitrite standard solution. The sample is introduced into the chip, droplets of 33 pL are created with a frequency of over 100 Hz for the direct injection and analysis by a quadrupole ICP-MS. The histogram of the recorded 238U+ ion intensities is shown in Figure 6. Three distinct peaks can be observed, corresponding to the number of droplets (1 to 3) that have been detected within the used acquisition time of 10 ms. The relative standard deviation (RSD) of the signal intensities illustrates the monodispersity of the droplets and is in the range of values reported in literature [3].

Figure 6: Histogram of recorded 238U+ ion signal intensities of droplets containing a 2 mg/kg Uranium standard solu-tion. The peak at 1.4*105 counts per second (cps) corresponds to a single droplet arriving at the ICP-MS within the se-lected acquisition time of 10 ms. The two peaks at 2.9*105 cps and 4.5*105 cps arise from two and three droplets arriv-

ing within the dwell time, respectively. The low RSD of the peaks proves the monodispersity of the droplets. Each peak is overlaid with a Gaussian fit curve to illustrate the accordance with the expected distribution of the signal.

CONCLUSION In conclusion, we have shown the direct coupling of droplet microfluidics and ICP-MS for the first time. In compari-

son to the commercial available discrete sample introduction systems the LADE chip is a cheap, easy to use and disposa-ble injection system for picoliter droplets. In future studies, the setup will be employed to analyze nanoparticles and sin-gle cells. ACKNOWLEDGEMENTS

Funding from the European Research Council under the 7th Framework Programme (ERC Starting Grant no. 203428 nµLIPIDS) is gratefully acknowledged. REFERENCES [1] F. Laborda, et al., “Selective identification, characterization and determination of dissolved silver (I) and silver na-

noparticles based on single particle detection by inductively coupled plasma mass spectrometry”, J. Anal. At. Spec-trom., vol. 26, pp. 1362-1371, 2011.

[2] S. C. Bendall, et al., “Single-cell mass cytometry of differential immune and drug responses across a human hema-topoietic continuum”, Science, vol. 332, pp. 687-696, 2011.

[3] S. Gschwind, et al., “Capabilities of inductively coupled plasma mass spectrometry for the detection of nanoparti-cles arried by monodisperse microdroplets”, J. Anal. At. Spectrom., vol. 26, pp. 1166-1174, 2011.

CONTACT *Prof. Dr. Petra S. Dittrich, tel: +41-4463-36893; dittrich@org.chem.ethz.ch

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