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US 2003/0194716 A1Published application
Device and method for performing syntheses, analylses or transport processes
AssigneeNone recorded
InventorMeinhard Knoll
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AssigneeNone recorded
InventorMeinhard Knoll
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The present invention relates to a device and a method for performing syntheses, analyses or transport processes with a process fluid. Devices and methods of this kind are used in the field of combinatory chemistry, in-situ synthesis, parallel synthesis, solid phase synthesis or the production of arrays, especially in the field of DNA synthesis, DNA analysis, for example as DNA chips, and in the field of peptide chemistry, pharmaceutical active substance screening, high throughput screening (HTS), pharmacogenomics and the like.
Device for performing syntheses, analyses or transport processes with a process fluid having a reaction chamber for accommodating the process fluid which is delimited on two of its opposite sides by a first and a second flat side wall, and having a feed aperture in the reaction chamber to feed the process fluid into the reaction chamber,
Device according to the preceding claim, characterised in that the control aperture tapers in the direction of the reaction chamber.
Device according to one of the preceding claims, characterised in that the first and/or the second side wall has at least one suction device for applying a negative pressure to the reaction chamber in the region of the suction device.
Device according to the preceding claim, characterised in that the suction device is configured as a suction port in the form of an opening in the side wall.
Device according to the preceding claim, characterised in that the suction ports have conically configured side walls.
Device according to the preceding claim, characterised in that the suction ports taper in the direction of the reaction chamber.
Device according to one of the three preceding claims, characterised in that the suction port is closed with a membrane which is permeable by the control fluid but not by the process fluid.
Device according to one of the preceding claims, characterised in that the control device for introducing the control fluid is configured as a die in the form of a mask for the selection of defined control apertures.
Device according to the preceding claim, characterised in that the suction device is disposed completely surrounding the control device in the surface plane of the reaction chamber.
Device according to one of the preceding claims, characterised by a blocking device for blocking the control device in such a way that no control fluid can be introduced into the reaction chamber by the control device.
Device according to the preceding claim, characterised in that the blocking device has a device for introducing a blocking fluid into the control aperture.
Device according to the preceding claim, characterised in that the device for introducing a blocking fluid is configured as a die which can be applied in the form of a mask to the control device.
Device according to the preceding claim, characterised in that the device for printing is a micro-drop printing device, an inkjet printing device or a screen printing device.
Device according to one of the preceding claims, characterized in that one side wall is configured as the analysis interface.
Device according to the preceding claim, characterised in that the analysis interface is light-permeable at least at pre-determined locations.
Device according to one of the two preceding claims, characterised in that the analysis interface is filled with analysis reagents at least at pre-determined locations on the side facing the reaction chamber.
Device according to one of the preceding claims, characterised in that one side wall is configured as the reaction interface.
Device according to the preceding claim, characterised in that the reaction interface is light-permeable at least at pre-determined locations.
Device according to one of the two preceding claims, characterised in that the reaction interface, at least at pre-determined locations on the side facing the reaction chamber, is covered with a substrate as the reagent or a substrate is inserted into the reaction interface at least at pre-determined locations.
Device according to one of the preceding claims, characterised in that between the two side walls extend webs which divide the reaction chamber into individual reaction chambers which are connected to one another and/or separated from one another.
Device according to one of the preceding claims, characterised in that the reaction chamber is divided into at least two interconnected reaction compartments, the first compartment being connected to at least one process media inflow and the second compartment to at least one process media outflow and each of the two compartments being provided with a control device.
Device according to the preceding claim, characterised in that each of the at least one process media inflows and/or each of the at least one process media outflows is connected to a valve.
Device according to one of the preceding claims, characterised in that the side walls consist at least partially of plastics material, glass, ceramics or the like.
Device according to one of the preceding claims, characterised in that the side walls have at least in parts a planar, porous or structured surface.
Device according to one of the preceding claims, characterised by a device for controlling the temperature of the reaction chamber and of the process fluid.
Device according to the preceding claim, characterised in that the device for controlling the temperature of the reaction chamber has a heating block, an infrared light source and/or a device for making a temperature-controlled fluid flow around the reaction chamber.
Device according to one of the preceding claims, characterised in that the membrane consists at least partially of silicon, Teflon, or the like.
Device according to one of the preceding claims, characterised in that the side wall consists at least partially of polymers, synthetic resin, polycarbonate, glass, ceramics or the like.
Device according to one of the preceding claims, characterised in that the control device has a thickness of 1 μm to 1 mm, the side walls, the reaction face or respectively the analysis interface have a thickness of several μm to several mm, the gas-permeable membrane has a thickness of several 100 nm to several 100 μm and/or the reaction chamber has a height of several 10 μm to 10 mm.
Device according to one of the preceding claims, characterised in that the control aperture has a diameter of between 1 μm and 10 mm.
Method according to the preceding claim, characterised in that the compartment is blocked by the control fluid or the process fluid is displaced from this compartment by the control fluid.
Method according to one of the preceding claims, characterized in that the introduction of control fluid into the reaction chamber via a control aperture is blocked by a blocking fluid being introduced into the control aperture.
Method according to one of the preceding claims, characterised in that the blocking fluid is introduced into the control aperture by electrospraying, dispensing methods, or printing methods such as micro-drop printing, inkjet printing or screen printing.
Method according to one of the two preceding claims, characterized in that a readily volatile medium is used as the blocking fluid.
Method according to one of the three preceding claims, characterized in that a liquid medium is used as the blocking fluid.
Method according to one of the preceding claims, characterised in that the blocking fluid is sucked away by additional channels integrated into the control interface.
Method according to one of the four preceding claims, characterised in that water, alcohol, THF or the like is used as the blocking fluid.
Method according to one of the preceding claims, characterised in that the control fluid is removed from the reaction chamber by the application of negative pressure.
Method according to one of the preceding claims, characterised in that a gas is used as the control fluid.
Method according to one of the preceding claims, characterised in that a noble gas is used as the control fluid.
Method according to one of the preceding claims, characterised in that argon or nitrogen is used as the control fluid.
Use according to the preceding claim for the synthesis of DNA, RNA, oligonucleotides, for epitope analysis, for antibody binding tests, for bioassays such as immunoassays for example.
Dependencies are inferred from the claim text.
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No related US applications are recorded in the indexed filing history.
Backward citations are indexed for grants only.
With fluid transport, e.g. in multi-compartment structures: by integrated microfluidic structures, i.e. dimensions of channels and chambers are…
Chemical, physical or physico-chemical processes in general; Their relevant apparatus: sequential or parallel reactions, e.g. for the synthesis of…
Chemical, physical or physico-chemical processes in general; Their relevant apparatus: microreactors, e.g. miniaturised or microfabricated reactors
Apparatus: features relating to reactor vessels
Term end not estimated
The present invention relates to a device and a method for performing syntheses, analyses or transport processes with a process fluid. Devices and methods of this kind are used in the field of combinatory chemistry, in-situ synthesis, parallel synthesis, solid phase synthesis or the production of arrays, especially in the field of DNA synthesis, DNA analysis for example as DNA chips and in the field of peptide chemistry, pharmaceutical active substance screening, high throughput screening (HTS), pharmacogenomics and the like. According to prior art, for example DNA arrays are produced by combinatory synthesis (in rows and columns) on a solid body. U.S. Pat. No. 5,700,637 discloses the production of cells for this purpose in a supporting material and coupling of nucleotides to this supporting material. To produce the variety of necessary oligonucleotides, a lithographic method is used for example in which more, than 400 different oligonucleotides are attached per cm2 (U.S. Pat. No. 5,744,305) or more than 1000 different oligonucleotides per cm2 (U.S. Pat. No. 5,445,934).
Furthermore, in prior art is known spot synthesis for producing arrays with oligonucleotides in which reagents for the synthesis are pipetted onto defined positions of a support. The washing and unblocking steps are performed by dipping the support into appropriate solutions. This is disclosed for example for sheets of cellulose paper as the support in Beck-Sickinger, G. et al “Kombinatorische Methoden in Chemie und Biologie” [=“Combinatory methods in chemistry and biology”], Spektrum Akademischer Verlag, Heidelberg, 1999, page 53.
Furthermore, the production of arrays with oligonucleotides with the aid of a moveable block having slots or channels for the supply of reagents is known from publications U.S. Pat. No. 5,561,646 and U.S. Pat. No. 5,885,837.
Some embodiments of the present invention are described below.
The figures show
FIGS. 1 to 11 different embodiments of the device according to the invention;
In FIG. 1a is represented a planar reaction chamber 7 which is delimited by two side walls 3 or respectively 1 and 2. The one side wall is here formed from a control plate 1 on which a gas-permeable membrane 2 is disposed on the side facing the reaction chamber 7. In the control plate 1 are inserted control apertures 5, through which the gas-permeable membrane 2 lies open to the outside. The other side wall of the reaction chamber 7 is formed by a plate-shaped analysis interface 3.
In the reaction chamber 7 is located a process fluid 4, which is only interrupted by gas bubbles 6 of a control fluid (control fluid domains 6, 6°).
According to the invention, the device is so operated that, with the aid of excess pressure, a control fluid can be brought into the reaction chamber through the control aperture 5 and the gas-permeable membrane 2. This control fluid then forms a control fluid domain 6 in the reaction chamber, which displaces the process fluid 4 from these sub-areas. Consequently no reaction of the process fluid 4 can take place there. This is also true during an exchange of the process fluid since the control fluid domains remain stationary as a result of the bubble adhesion.