Download monolithic integrated glass micronozzle emitters on silicon for nano

MONOLITHIC INTEGRATED GLASS MICRONOZZLE EMITTERS ON
SILICON FOR NANO-ELECTROSPRAY IONIZATION MASS
SPECTROMETRY
L. Duan, Y. Liu and L. Yobas*
The Hong Kong University of Science and Technology, Hong Kong, P.R. CHINA
ABSTRACT
We demonstrate a novel structure of micronozzle emitters for nano-electrospray ionization mass
spectrometry. The monolithic emitters are made of glass micronozzles integrated on silicon in a batchfabrication process; self-enclosed glass capillaries were formed using a doped glass layer deposited at a
non-conformal thickness profile across narrow trenches and then subjected to thermal reflow for shape
transformation. A dry release step revealed micronozzles protruding from the substrate. This report is the
first account of applying this unique process to obtain integrated emitters that are highly robust and
feature a smooth interior surface that is free of etching roughness.
KEYWORDS: Electrospray, Ionization, Micronozzle, Spectrometry
INTRODUCTION
Mass spectrometry is a powerful analytical technique in fields such as proteomics and metabolomics.
It can effectively determine the elemental composition of molecules or elucidate their structure based on
the mass-to-charge ratio of ions. To ionize its constituents, the sample has to undergo vaporization first. A
popular “soft” technique capable of ionizing macromolecules without fragmenting them is electrospray
ionization (ESI) and delivered through an emitter tip, i.e. a sharp nozzle. Microfabricated monolithic
emitters have become the center of attention owing to their merits such as batch fabrication, microfluidic
integration (with upstream analytical modules such as chromatography), and massive parallelization [1].
However, most known monolithic emitters are either made of hydrophobic materials that exhibit strong
affinity to proteins or incompatible with organic solvents, or simply limited in microfluidic integration.
Here, based on an innovative process, we demonstrate monolithic glass micronozzle emitters on silicon.
These micronozzles are extensions of integrated glass capillaries self-enclosed in silicon trenches under
non-conformal glass deposition and then shape-transformed through glass thermal reflow, Fig. 1 [2,3].
Figure 1: 3D rendering of the emitter structure based on the self-enclosed glass capillaries integrated on
silicon by using non-conformal glass deposition and thermal reflow.
978-0-9798064-8-3/µTAS 2015/$20©15CBMS-0001
1749
19th International Conference on Miniaturized
Systems for Chemistry and Life Sciences
October 25-29, 2015, Gyeongju, KOREA
EXPERIMENTAL
The emitters were realized on a p-type (100)-oriented 4-inch silicon wafer using a batch fabrication
process, which began with lithographically forming trenches 3 µm wide and deep through deep reactive
ion etch (DRIE), Fig. 2. A phosphorus-doped glass (PSG) layer was then deposited at a nominal thickness
of 5.5 µm, enclosing the trenches through low-pressure CVD (180 mTorr, 420 °C). The thermal anneal
step that transformed the enclosed trenches into cylindrical capillaries was performed at 1000 °C for 60
min. A second lithography step was applied and followed by advanced oxide etch (AOE) and DRIE to
define a 25-µm-deep supply channel while opening up the capillary ends and outlining the capillary
segments to be suspended. The process involved a third and final lithography step applied on the wafer
backside along with AOE and DRIE to release the suspended capillary segments from bulk silicon.
Figure 2: Major fabrication steps (a) trench etch (b) PSG deposition and thermal reflow (c,d) front and
backside lithography and AOE/DRIE etch PSG/silicon.
RESULTS AND DISCUSSION
Fig. 3 shows micronozzle emitters before and after bonding a polydimethylsiloxane (PDMS) cover.
Figure 3: Microfabricated (a) single & multinozzle chips. (b) An emitter before and after PDMS bonding.
The emitters featuring either a single or multiple (five or ten) micronozzles, all 100-µm long, were
evaluated by measuring total electrospray current against increasing voltages for a fixed pump set value at
80 nL/min per micronozzle, Fig. 4a. The total current for a single-micronozzle emitter exhibited plateau
regions (arrows), each referring to a specific mode: pulsating (1.7 kV), cone-jet (2.1 kV) and multi-jet
(2.6 kV). Only a single plateau did appear for those emitters with multiple micronozzles, corresponding to
the cone-jet mode and occurred at relatively high voltages (> 2.8 kV). Subsequently, the dependence
between the electrospray current and the total flow rate was investigated for each emitter at a specific
plateau region corresponding to the cone-jet mode, Fig. 4b. The emitter featuring ten micronozzles was
evaluated through an ion trap mass spectrometer (LTQ Velos) and benchmarked against a commercial tip
(New Objective) for ionizing standard peptide Glu-fibrinopeptide B (GFP B), Fig. 5.
1750
Figure 4: Total ESI currents (a) as a function of applied voltage spraying with the pump set at 80 nL/min
and (b) at distinct flow rates in the cone-jet spraying mode. The error bars: standard deviations (n=4).
Figure 5: GFP B (1 µM) mass spectra: 10-nozzle emitter at 2.1 kV and 0.8 µL/min (inset; arrows Taylor
cones); right inset commercial emitter, 1.5 kV, no flow applied. MS Cone: 40 V.
CONCLUSION
We have demonstrated monolithic glass micronozzles on silicon for nano-electrospray ionization
mass spectrometry. These emitters are currently undergoing integration with a microfluidic system featuring a capillary-well motif validated for gel-free electrophoretic separation of macromolecules [3].
ACKNOWLEDGEMENTS
This work was funded by a grant from the Research Grant Council of Hong Kong (No. GRF621513).
REFERENCES
[1] T. Sikanen, S. Franssila, T. J. Kauppila, R. Kostiainen, T. Kotiaho, and R. A. Ketola, "Microchip
Technology in Mass Spectrometry," Mass Spectrom Rev, 29, 351-391, 2010.
[2] Y. Liu, and L. Yobas, “Cylindrical Glass Nanocapillaries Patterned via Coarse Lithography (> 1 µm)
for Biomicrofluidic Applications,”, Biomicrofluidics, 6, 046502, 2012.
[3] Z. Cao, and L. Yobas, “Gel-Free Electrophoresis of DNA and Proteins on Chips Featuring a 70 nm
Capillary–Well Motif,” ACS Nano, 9, 427-435, 2015.
CONTACT
* Levent Yobas ; phone: +852-2358-7068; [email protected]
1751