Miniaturized fluid transfer device

Details Miniaturized fluid transfer device Miniaturized fluid transfer device

2000-11-02

2002-11-12

Douglas, Lisa A. (Department: 3752)

Fluid sprinkling, spraying, and diffusing

Including supply holder for material

Fluid pressure discharge means

C239S416400, C239S423000

Reexamination Certificate

active

06478238

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates, in general, to fluid transfer apparatus, and more particularly to miniature, pneumatically assisted electrospray devices.
BACKGROUND OF THE INVENTION
Miniaturized fluid transfer devices offer exciting opportunities for a wide range of applications. For example, such devices are extremely useful in the field of analytical chemistry and for convenience will be described herein with respect to electrospray apparatus for use in mass spectrometry. However, it will be understood that such devices are not limited to this particular application.
Although the application of chip-based analytical devices for zone electrophoresis separation of analytes with conventional spectroscopic detectors was first demonstrated many years ago, on-going developments have demonstrated impressive applications for analytical devices involving capillary electrophoresis (CE) particularly when performed on a chip-based substrate. Some recent reports have demonstrated CE separations within time frames of seconds and even milliseconds. Each of these reports has employed various spectroscopic detectors and used direct detection of analytes on the chip.
Atmospheric pressure ionization (API) mass spectrometry (MS) techniques also provide an important, alternative detection system for chip-based devices. Consequently, efforts to couple this technology with chip-based sample handling systems has attracted considerable recent interest. Developments in miniaturized chip-based devices for analytical applications that have appeared over the past decade suggest these devices coupled to API MS systems could provide some useful analytical advances.
Attempts to couple mass spectrometry with a chip-based fluid channel have, to date, required that the latter deliver the analyte via an electrospray plume directed to the ion sampling orifice of an API mass spectrometer. A strategy for producing a microelectrospray plume from the chip has evolved from direct spraying from the flat edge of the chip to improved means of producing an electrospray plume. One of these was an integrated miniaturized pneumatic nebulizer coupled via a subatmospheric liquid junction electrospray interface, while another was a pulled glass capillary centered in a carefully drilled flat-bottomed hole centered with the exit of a microfabricated CE channel in a glass substrate. Additional reports have included a sleeve to support the sprayer capillary on the edge of the chip as well as disposable emitters for CE/MS. Other developments have included gluing a pulled capillary sprayer on the flat, larger surface of the chip aligned with the CE channel. An alternative approach that may be applicable to chip-based separations has also been reported which employs a microfabricated monolithic nozzle surrounded by an annular cavity on the surface of a silicon substrate. In this device the fluid is delivered from the backside of a silicon chip substrate using fluid flows of a few hundred nanoliters per minute via a through-chip channel which terminates in a nanoelectrospray nozzle.
The foregoing developments demonstrate the continuing need for improved fluid transfer devices for use not only in electrophoresis and other analytical applications, but in numerous other fluid transfer applications in both micro and macro scales.
SUMMARY OF THE INVENTION
In a preferred embodiment, the fluid transfer device of the present invention is a miniature, pneumatically-assisted electrospray source that uses the suction effects of electrospray and the Bernoulli effect to pull a solution into a sprayer tube. The solution is provided by a concentric supply tube around the sprayer tube, with the supply tube being sealed at a front, or sprayer, end and open at the other, or back, end and which is slightly shorter than the sprayer tube. Solution supplied through a small hole in the supply tube near the middle of the tube flows rearwardly and protrudes out the back end of the supply tube, where it is sucked into the sprayer tube. The solution then is electrosprayed from the front end with pneumatic assistance. The solution has some surface tension where it protrudes from the back of the sprayer tube and this protrusion forms a free-standing liquid junction which can be used to make contact with a liquid or other material which may, for example, be within a separation channel in a glass, plastic or other based separation device. The resulting liquid junction at the back of the sprayer tube is thus free standing, its existence, size and form being dependent upon the flow rate, the viscosity, and the surface tension of the solution, the diameters of the various tubes used and their composition, the voltage on and the nature of the sprayer, and the characteristics of the pneumatic nebulizing portion of the sprayer.
In one application of the invention, the liquid junction of the device may be used to effectively couple a miniaturized condensed phase separation system; e.g., chip-based capillary electrophoresis (CE), capillary electrochromatography (CEC), or nano scale high performance liquid chromatography (HPLC), to the miniaturized spraying device without interfering with the separation device. Flow rates and voltages are selected such that the rate of solution fed to the liquid junction via an external pump just matches the rate of removal of the solution by the sprayer. By using a properly sized decoupling resistor between the metal sprayer tube to ground, condensed phase separations such as capillary electrophoresis (CE), capillary electro chromatography (CEC), or nano scale high performance liquid chromatography (HPLC) can be performed while maintaining independent spraying and separation conditions.
There are many other potential applications for the fluid transfer device of this invention, such as a direct coupling via the liquid junction to the surface of a thin layer chromatography (TLC) plate or to a single or two dimensional SDS PAGE plate for the direct analysis of chemical entities contained on the plate. Such additional applications could be of considerable use in forensic drug analysis applications or the proteomics field where important chemicals of interest may be characterized by electrospray-mass spectrometry.


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