Fluid sprinkling – spraying – and diffusing – Electrostatic type
Reexamination Certificate
2000-05-15
2002-11-19
Evans, Robin O. (Department: 3752)
Fluid sprinkling, spraying, and diffusing
Electrostatic type
C239S589000, C239S691000, C239S692000
Reexamination Certificate
active
06481648
ABSTRACT:
The invention relates in general to microchip laboratory systems which serve to carry out chemical, chemical-physical, physical, biochemical and/or biological processes, in particular for the analysis or synthesis of substances on a carrier which features a microfluidic structure. The essentially flat carrier in this situation features a micro-channel structure, by means of which the substances are capable of movement in accordance with the channel structure under the imposition of a potential particularly an electrical potential. In particular, the invention relates to such microchip systems in which a micro spray tip is provided for spraying substances to the outside particularly for the insertion spraying of substances into a mass spectrometer. In addition, the invention relates to a process for the manufacture of a microchip featuring such a micro spray tip, as well as a device for handling such a microchip.
The rapid progress in the sector in question can best be illustrated by way of the corresponding developments in the microelectronics sector. In the chemical analysis sector, too, not least with regard to clinical outpatient diagnosis, there is a substantial demand for existing stationary laboratory equipment to be integrated into portable systems, or for such systems to be miniaturised accordingly. An overview of the latest developments in the sector of laboratory microchip technology can be found in a collection of pertinent specialist publications edited by A. van den Berg and P. Bergveld under the title “Micrototal Analysis Systems”, published by Kiuwer, Academic Publishers, Netherlands, 1995. The starting point for these developments was the already established method of what is referred to as “capillary electrophoresis”, with which efforts have already been made in the past to implement the system on a planary glass microstructure.
FIG. 1
shows a conventional laboratory microchip. As shown on the upper surface of a substrate or carrier
10
, microfluidic structures are applied, which serve to accommodate and transport substances. The carrier
10
may be made, for example, of glass or silicon, whereby the structures can be created by means of a chemical or laser-supported etching process. To accommodate a substance which is to be examined (referred to hereinafter as the “substance specimen”) on the microchip, one or more indentations
11
are provided on the carrier, which serve as a reservoir for the individual substance specimen. For the purpose of conducting the experiment, the substance specimen is initially moved along a transport channel
15
on the microchip. In the present embodiment, the transport channel is formed by a V-shaped groove. There are, however, in principle other embodiments of the transport channel possible, such as rectangular or circular profiled cut-outs or grooves. Other depressions
12
, serving likewise as substance reservoirs or wells, accommodate the reagents required for the performance of the experiment. In the present example, this involves two different substances, these being initially conducted by means of corresponding transport channels
16
to a point of intersection
17
, where they intermix and, after chemical analysis or synthesis has been carried out if appropriate, they form the product which is ultimately to be used. At a further point of intersection
18
, this reagent then encounters the substance specimen which is to be examined, whereby both substances are likewise intermixed.
The substance which is formed in this overall manner then runs through a meander-shaped transport section
19
, which serves essentially to enlarge artificially the lengths of the distances available for the reaction between the substance specimen and the reagent. In the present example, in a further indentation
13
, formed as a substance reservoir or well, an additional reagent is contained which is conducted to the substance mixture which already pertains, at a further point of intersection
21
.
In the present example, the substance reaction which is actually to be examined takes place immediately adjacent to the point of intersection in reference
21
. The detection of this substance reaction then takes place within a measurement field or area
22
of the transport channel by means of a detector, not shown here, for preference free of contact. An appropriate detector may in this case be arranged above or below the area
22
. Once the substance has run through said area
22
, it is conducted to a further indentation
14
, which represents a substance sink for the substance waste residues formed overall during the reaction.
Finally, depressions
23
are provided on the microchip which function as contact surfaces for the application of electrodes, and which in turn allow for the imposition on the chip of the electrical voltages, and high voltages in particular, which are required for the operation of the chip. As an alternative, the contact for the microchip can also be provided by the introduction of an appropriate electrode to directly into the depressions
11
,
12
,
13
,
14
provided for the accommodation of the substances. By means of a suitable arrangement of the electrodes
23
along the transport channels
15
,
16
,
19
,
20
and a corresponding temporal and/or strength concordance of the fields used, a situation can now be attained in which the movement of the individual substances is effected in accordance with a temporal and volume profile which can be precisely predetermined, with the result that the kinetics of the reaction process taken as the basis in each case can be most precisely taken into consideration, and can be maintained respectively.
In the case of the movement of the substances by means of gas pressure (not shown here) within the microfluidic structure, it is necessary for the transport channels to be designed as conduits endosed all round, for example as hollow channels with predetermined cross-sections. In such an embodiment, it is therefore necessary for the depressions
23
to be designed in such a way that suitable pressure supply lines engage in them, duly sealed, in order for a pressure medium, such as a noble gas, to be introduced into the transport channels.
Miniaturisation of the microchips also allows for a substantial shortening of the transport paths for the substances, especially between the introduction point for the substances and the individual detection point for the measurement of a chemical reaction which is to be effected (see FIG.
1
). From the sector of liquid chromatography and electrophoresis the principle is further known of a substance separation being implemented more rapidly in such systems, and therefore of the results of experiments likewise being provided more rapidly, and for the individual components to be separated with higher resolution than is possible in conventional systems. In addition to this, microminiaturised laboratory systems also allow for a substantial reduction in the consumption of substances, in particular of reagents, as well as a substantially more efficient mixing of the substance components.
A laboratory microchip of the type shown in
FIG. 1
has been described, for example, in U.S. Pat. No. 5,858,195. The movement of the substances in the channels integrated on the microchip is controlled by means of electric fields, which are imposed along the transport channels. Because of the highly precise control of the substance movement which is achieved by this, and the very precise metering ability of the substance masses moved in each case, the substances can be mixed or separated precisely in relation to the desired stoichiometry, or physical-chemical reactions can be induced. The movement of the substances is effected in this case on the basis of what is referred to as electro-osmosis; i.e. the movement of individual substances within a substance mixture incurred by an electrical potential gradient. Substances move in electrical fields on the one hand due to their space charge. The space charge can for example be controlled by an appropriate chemically acidi
Agilent Technologie,s Inc.
Evans Robin O.
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