Semiconductor device manufacturing: process – Making device or circuit responsive to nonelectrical signal
Reexamination Certificate
2002-09-17
2004-06-15
Tsai, H. Jey (Department: 2812)
Semiconductor device manufacturing: process
Making device or circuit responsive to nonelectrical signal
C438S689000, C438S719000, C438S753000
Reexamination Certificate
active
06750076
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates generally to the fabrication of an integrated miniaturized fluidic system fabricated using Micro-ElectroMechanical System (MEMS) technology, particularly to the improved fabrication of a microsized electrospray nozzle.
BACKGROUND OF THE INVENTION
Microchip-based separation devices have been developed for rapid analysis of large numbers of samples. Compared to other conventional separation devices, these microchip-based separation devices have higher sample throughput, reduced sample and reagent consumption, and reduced chemical waste. The liquid flow rates for microchip-based separation devices range from approximately 1-300 nanoliters per minute for most applications. Examples of microchip-based separation devices include those for capillary electrophoresis (“CE”), capillary electrochromatography (“CEC”) and high-performance liquid chromatography (“HPLC”) include Harrison et al.,
Science
261:859-97 (1993); Jacobson et al.,
Anal. Chem.
66:1114-18 (1994), Jacobson et al.,
Anal. Chem.
66:2369-73 (1994), Kutter et al.,
Anal. Chem.
69:5165-71 (1997) and He et al.,
Anal. Chem.
70:3790-97 (1998). Such separation devices are capable of fast analyses and provide improved precision and reliability compared to other conventional analytical instruments.
The work of He et al.,
Anal. Chem.
70:3790-97 (1998) demonstrates some of the types of structures that can be fabricated in a glass substrate. This work shows that co-located monolithic support structures (or posts) can be etched reproducibly in a glass substrate using reactive ion etching (RIE) techniques. Currently, anisotropic RIE techniques for glass substrates are limited to etching features that are 20 &mgr;m or less in depth. This work shows rectangular 5 &mgr;m by 5 &mgr;m width by 10 &mgr;m in depth posts and stated that deeper structures were difficult to achieve. The posts are also separated by 1.5 &mgr;m. The posts supports the stationary phase just as with the particles in LC and CEC columns. An advantage to the posts over conventional LC and CEC is that the stationary phase support structures are monolithic with the substrate and therefore, immobile.
He et. al., also describes the importance of maintaining a constant cross-sectional area across the entire length of the separation channel. Large variations in the cross-sectional area can create pressure drops in pressure driven flow systems. In electrokinetically driven flow systems, large variations in the cross-sectional area along the length of a separation channel can create flow restrictions that result in bubble formation in the separation channel. Since the fluid flowing through the separation channel functions as the source and carrier of the mobile solvated ions, formation of a bubble in a separation channel will result in the disruption of the electroosmotic flow.
Electrospray ionization provides for the atmospheric pressure ionization of a liquid sample. The electrospray process creates highly-charged droplets that, under evaporation, create ions representative of the species contained in the solution. An ion-sampling orifice of a mass spectrometer may be used to sample these gas phase ions for mass analysis. When a positive voltage is applied to the tip of the capillary relative to an extracting electrode, such as one provided at the ion-sampling orifice of a mass spectrometer, the electric field causes positively-charged ions in the fluid to migrate to the surface of the fluid at the tip of the capillary. When a negative voltage is applied to the tip of the capillary relative to an extracting electrode, such as one provided at the ion-sampling orifice to the mass spectrometer, the electric field causes negatively-charged ions in the fluid to migrate to the surface of the fluid at the tip of the capillary.
When the repulsion force of the solvated ions exceeds the surface tension of the fluid being electrosprayed, a volume of the fluid is pulled into the shape of a cone, known as a Taylor cone, which extends from the tip of the capillary. A liquid jet extends from the tip of the Taylor cone and becomes unstable and generates charged-droplets. These small charged droplets are drawn toward the extracting electrode. The small droplets are highly-charged and solvent evaporation from the droplets results in the excess charge in the droplet residing on the analyte molecules in the electrosprayed fluid. The charged molecules or ions are drawn through the ion-sampling orifice of the mass spectrometer for mass analysis. This phenomenon has been described, for example, by Dole et al.,
Chem. Phys.
49:2240 (1968) and Yamashita et al.,
J. Phys. Chem.
88:4451 (1984). The potential voltage (“V”) required to initiate an electrospray is dependent on the surface tension of the solution as described by, for example, Smith,
IEEE Trans. Ind. Appl.
1986, IA-22:527-35 (1986). Typically, the electric field is on the order of approximately 10
6
V/m. The physical size of the capillary and the fluid surface tension determines the density of electric field lines necessary to initiate electrospray.
When the repulsion force of the solvated ions is not sufficient to overcome the surface tension of the fluid exiting the tip of the capillary, large poorly charged droplets are formed. Fluid droplets are produced when the electrical potential difference applied between a conductive or partly conductive fluid exiting a capillary and an electrode is not sufficient to overcome the fluid surface tension to form a Taylor cone.
Electrospray Ionization Mass Spectrometry: Fundamentals, Instrumentation, and Applications
, edited by R. B. Cole, ISBN 0-471-14564-5, John Wiley & Sons, Inc., New York summarizes much of the fundamental studies of electrospray. Several mathematical models have been generated to explain the principals governing electrospray. Equation 1 defines the electric field E
c
at the tip of a capillary of radius r
c
with an applied voltage V
c
at a distance d from a counter electrode held at ground potential:
E
c
=
2
V
c
r
c
ln
(
4
d
/
r
c
)
(
1
)
The electric field E
on
required for the formation of a Taylor cone and liquid jet of a fluid flowing to the tip of this capillary is approximated as:
E
on
≈
(
2
γcosθ
ϵ
o
r
c
)
1
/
2
(
2
)
where &ggr; is the surface tension of the fluid, &thgr; is the half-angle of the Taylor cone and &egr;
0
is the permittivity of vacuum. Equation 3 is derived by combining equations 1 and 2 and approximates the onset voltage V
on
required to initiate an electrospray of a fluid from a capillary:
V
on
≈
(
r
c
γcosθ
2
ϵ
0
)
1
/
2
ln
(
4
d
/
r
c
)
(
3
)
As can be seen by examination of equation 3, the required onset voltage is more dependent on the capillary radius than the distance from the counter-electrode.
It would be desirable to define an electrospray device that could form a stable electrospray of all fluids commonly used in CE, CEC, and LC. The surface tension of solvents commonly used as the mobile phase for these separations range from 100% aqueous (&ggr;=0.073 N/m) to 100% methanol (&ggr;=0.0226 N/m). As the surface tension of the electrospray fluid increases, a higher onset voltage is required to initiate an electrospray for a fixed capillary diameter. As an example, a capillary with a tip diameter of 14 &mgr;m is required to electrospray 100% aqueous solutions with an onset voltage of 1000 V. The work of M. S. Wilm et al.,
Int. J. Mass Spectrom. Ion Processes
136:167-80 (1994), first demonstrates nanoelectrospray from a fused-silica capillary pulled to an outer diameter of 5 &mgr;m at a flow rate of 25 nL/min. Specifically, a nanoelectrospray at 25 nL/min was achieved from a 2 &mgr;m inner diameter and 5 &mgr;m outer diameter pulled fused-silica capillary with 600-700 V at a distance of 1-2 mm from the ion-sampling orifice of an electrospray equipped mass spectrometer.
Electrospray in front of an ion-sampling orifice of an API mass spectr
Advion Biosciences, Inc.
Nixon & Peabody LLP
Tsai H. Jey
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