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Researchers Submit Patent Application, "Dispensing and Metering System, in Particular of Substances in Microfluidic Systems, and Also Method and...

June 17, 2014



Researchers Submit Patent Application, "Dispensing and Metering System, in Particular of Substances in Microfluidic Systems, and Also Method and Cartridge Having the Dispensing and Metering System", f

By a News Reporter-Staff News Editor at Life Science Weekly -- From Washington, D.C., NewsRx journalists report that a patent application by the inventors Daub, Martina (Weissach, DE); Steigert, Juergen (Stuttgart, DE); Hoehl, Melanie (Ditzingen, DE), filed on November 27, 2013, was made available online on June 5, 2014 (see also Robert Bosch GmbH).

The patent's assignee is Robert Bosch GmbH.

News editors obtained the following quote from the background information supplied by the inventors: "The basis for carrying out biochemical processes is, in particular, the handling of liquids. Typically, this handling is carried out manually with aids, such as pipettes, reaction vessels, active probe surfaces or laboratory instruments. These processes are already partially automated by means of pipetting robots or special instruments.

"Lab-on-a-chip systems (also designated as vest pocket laboratory or chip laboratory) accommodate the entire functionality of a macroscopic laboratory on a plastic substrate only the size of a credit card. Lab-on-a-chip systems are typically composed of two main components. A test carrier contains structures and mechanisms for implementing the basic fluidic operations (for example, mixers), which may be composed of passive components, such as ducts, reaction chambers and preceding reagents, or else of active components, such as valves or pumps. The second main component comprises actuation, detection and control units. Such systems make it possible to carry out biochemical processes in a fully automated way.

"US 2005/0191708 A1 shows a microfluidic system in which small liquid volumes can be moved or mixed by virtue of materials which are heated by means of microwaves."

As a supplement to the background information on this patent application, NewsRx correspondents also obtained the inventors' summary information for this patent application: "The dispensing and metering system, the cartridge, and the method disclosed herein have, as compared with conventional solutions, the advantage that stored substances (in any state of aggregation) can be released in a directed way by actuation or by contact with further substances in a fluid, the stored substance being located in the fluid or adjacently to the fluid in an initial configuration of the dispensing and metering system, and a separation element preventing the intermixing of stored substance and fluid until actuation upon the separation element occurs.

"The present metering and dispensing system can advantageously be used for the storage of substances, for their directed release and at the same time as a metering, dispensing and modeling system. In general terms, the present metering and dispensing system is suitable especially for the directed matching of the reaction kinetics of the fluid with the stored substance dispensed, the reaction kinetics being controllable primarily by the choice of material for the separation element. Owing to the choice of material for the separation element and directed setting of its properties (for example, surface quality, topography, density and geometry), and to the arrangement of the separation element (for example, spatially or geometrically) and/or due to a change in external actuation, the present metering and dispensing system can advantageously be activated or its dispensing behavior modified in a directed way, independently of instrument activation methods, such as, for example, the rotational speed of the centrifuge or the utilization of pneumatic valves.

"The present metering and dispensing system may, for example, be employed for chemical reactions, biological reactions (in the manner of reagent storage, kinetic assays, for example fluorescence, immuno or enzyme steps) and other processes (enzyme or reagent for kinetic enzymatic reaction in a cartridge with a 'ballpoint mechanism', as it is known).

"Furthermore, in the present dispensing and metering system, the hitherto necessary complicated welding, sealing or thermal or ultrasonic bonding of chambers for specific reagents (by, for example, a metal foil) may advantageously be dispensed with. Thus, the present metering and dispensing system can be implemented cost-effectively in a technically simple way and can easily be integrated into existing devices and instruments.

"Actuation is to be understood to mean any type of directed and/or predetermined action upon the separation element which ensures that the stored substance is dispensed to the liquid. In principle, actuation may also take place as a result of the contact of the separation element with the stored substance and/or the fluid. Preferably, however, actuation upon the separation element takes place from outside the dispensing and metering system (for example, in the manner of heat or radiation or contact with a substance).

"In the present context, 'fluid' and 'stored substance' mean a liquid, a gas, a particle (or a plurality of particles) or a solid material.

"Advantageous refinements of the disclosure may be gathered from the subclaims.

"According to one refinement of the dispensing and metering system according to the disclosure, actuation comprises physical or chemical stimulation of the separation element. Examples given of physical stimulation may be an (external) force, centrifugal force, (hydrostatic) pressure or electrical energy. Examples given for chemical stimulation may be the pH value, solubility, surface size and temperature of the stored substance, separation element or fluid. Alternatively and/or additionally, actuation may also comprise the contact of the stored substance with the fluid.

"According to a further refinement of the dispensing and metering system according to the disclosure, the dispensing of the stored substance to the fluid after the actuation of the separation element takes place in a continuously metered manner, discretely, with a time delay or in multiple stages over a predefined period of time. Continuously metered dispensing is intended to describe dispensing at an essentially constant dispensing rate of the stored substance over the predefined period of time. Discrete dispensing is intended to describe essentially once-only dispensing of the stored substance over the predefined period of time. Time-delayed dispensing is intended to describe dispensing of the stored substance after a predetermined delay time as a follow-up to the actuation of the separation element over the predefined period of time. The selected dispensing rate for time-delayed dispensing may be constant or variable as a function of the material and of the properties of the separation element. Multiple-stage dispensing is intended to describe multiple dispensing of the stored substance over the predefined period of time. The selected dispensing rate for multiple-stage dispensing may again be constant or variable as a function of the material and of the properties of the separation element.

"According to a further refinement of the dispensing and metering system according to the disclosure, the separation element is composed of a bioprocess-compatible material. What may be considered as material for the separation element is, in principle, all materials which become unstable as a result of contact with substances and/or by actuation. These include, for example, (special) polymers, wax (for example, paraffins), materials for the production of drug capsules (for example, gelatine, decomposable polymers, sugar, sugar derivatives). A bioprocess-compatible material is distinguished in that it is degradable and harmless to health, and there is no appreciable participation of the material in a (chemical) reaction of stored substance and fluid. Interactions of the separation element or of the predetermined breaking point with the fluid and with other substances used in the dispensing and metering system can thereby be minimized or avoided.

"According to a further refinement of the dispensing and metering system according to the disclosure, the separation element completely surrounds the stored substance in the initial configuration. Thus, for example, the stored substance can be enclosed on all sides in a capsule. The capsule may have a round, oval or angular casing or may have any other form. The capsule may be formed from the material of the separation element completely or else only partially.

"According to a further refinement of the dispensing and metering system according to the disclosure, the separation element partially surrounds the stored substance in the initial configuration. In a dispensing and metering system of this type, the stored substance is surrounded, for example, on only one side by the separation element. This may be a configuration in which a duct or a chamber open on one side receives in each case the fluid and the stored substance, the fluid and the stored substance being separated from one another in the initial configuration by the intermediate separation element. In addition to this, the stored substance may also be surrounded by the separation element on more than one side, as is the case, for example, in an L-shaped or T-shaped branch of a duct or pipe.

"According to a further refinement of the dispensing and metering system according to the disclosure, the actuation of the separation element ensures permeability of the separation element for the stored substance. In this case, actuation causes a directed modification in the material make-up and/or in the surface of the separation element, so that the stored substance can pass through the separation element and subsequently comes into contact with the fluid. Thus, permeability of the separation element can be achieved as a function of selected actuation parameters (for example, temperature, pressure, pH value, etc.). Alternatively, the actuation of the separation element can ensure an essentially complete dissolution or destruction of the separation element, in which case the stored substance is dispensed only once and completely to the fluid.

"According to a further refinement of the dispensing and metering system according to the disclosure, the separation element has a multilayer make-up. In this case, for example, an outer layer may be formed in such a way that dispensing of the stored substance is prevented until the actuation of the separation element occurs, the outer layer being, for example, essentially completely or at least partially broken down or destroyed as a result of actuation. A layer lying underneath may be formed in such a way that it remains essentially unchanged after the actuation of the separation element, said actuation being designed in such a way that it implements the desired dispensing behavior of the stored substance to the fluid over time.

"According to a further refinement of the dispensing and metering system according to the disclosure, the separation element has a first material and a second material and, in the initial configuration, both the first material and the second material are in contact with the fluid. The present dispensing and metering system can thus be formed, for example, by the mixing or alternating arrangement of the at least two materials for the separation element or by the connection of the two materials, while the two materials may have different material properties (for example, different strength, variability in stability upon contact with the fluid (for example, solubility), different surface size (for example, grain size), dependence upon actuation parameters (for example, temperature dependence, pressure dependence, etc.)). The two materials for the separation element may be formed from different stock, but they may also be formed by one and the same stock which, however, has in each case different properties in compliance with the intended use of the dispensing and metering system. A combination of a multilayer make-up and of a make-up by means of a plurality of materials is also possible for the separation element.

"According to a further refinement of the dispensing and metering system according to the disclosure, the separation element has a predetermined breaking point. In this case, the predetermined breaking point is preferably composed of a bioprocess-compatible material, such as, for example, sugar or gelatine. Interactions of the separation element or of the predetermined breaking point with the fluid and with other substances used in the dispensing and metering system can thereby be minimized or avoided. In addition to this, the material for the predetermined breaking point may be selected in such a way that it is, for example, temperature- and/or liquid-dependent.

"In a dispensing and metering arrangement, at least two metering and dispensing systems according to the disclosure may also be nested, placed one above the other, arranged in cascade form and connected in parallel and/or in series.

"According to a further embodiment, a cartridge is claimed, having a dispensing and metering system, a housing of the cartridge, a drum which has at least one chamber, the dispensing and metering system being arranged inside the drum.

"The present cartridge can advantageously be used for releasing a stored substance into the fluid, such as is necessary, for example, in the medical analysis and/or diagnosis of a sample material. Thus, in this case, for example, proteinase K can be released in the lysis step over a specific period of time or for incubation, for example in the lysis step, over a defined period of time.

"According to a further alternative embodiment, a method for producing a component is claimed, which has the following steps: provision of a dispensing and metering system according to the disclosure, production of a component by dispensing the stored substance to the fluid, the component being formed from the stored substance dispensed and from the fluid after the actuation of the separation element.

"In the present context, 'component' means a liquid, a gas, a solid particle (or a multiplicity of solid particles) or a solid material.

"The present method can advantageously be used for the production of substances of all kinds, during the production of which a separation of the stored substance and fluid is first necessary. The present method is therefore suitable, in particular, for the production of chemicals, biological products and medical substances. Depending on the dispensing kinetics of the stored substance, the respective processes (for example, chemical, physical and biological reactions) can be regulated in a directed way. For example, the present dispensing and metering system may also be employed in processes in which, because of low stability, the reaction partners involved can be brought together only shortly before use. These include, for example, the mixing of buffers, enzymes, vitamins and dyes with liquids, although other reaction partners may also be envisaged.

"According to a further refinement of the method according to the disclosure for producing a component, the dispensing of the stored substance to the fluid after the actuation of the separation element takes place in a continuously metered manner, discretely, with a time delay or in multiple stages over a predefined period of time. Continuously metered dispensing is intended to describe dispensing at an essentially constant dispensing rate of the stored substance over the predefined period of time. Discrete dispensing is intended to describe essentially once-only dispensing of the stored substance over the predefined period of time. Time-delayed dispensing is intended to describe dispensing of the stored substance after a predetermined delay time as a follow-up to the actuation of the separation element over the predefined period of time. The selected dispensing rate for time-delayed dispensing may be constant or variable as a function of the material and of the properties of the separation element. Multiple-stage dispensing is intended to describe multiple dispensing of the stored substance over the predefined period of time. The selected dispensing rate for multiple-stage dispensing may again be constant or variable as a function of the material and of the properties of the separation element.

BRIEF DESCRIPTION OF THE DRAWINGS

"Exemplary embodiments of the disclosure are illustrated in the figures of the drawings and are explained in more detail in the following description.

"In the drawings:

"FIG. 1 shows diagrammatically a side view of a dispensing and metering system according to a first exemplary embodiment of the present disclosure;

"FIG. 2 shows a top view of a dispensing and metering system according to a second exemplary embodiment of the present disclosure;

"FIG. 3 shows a top view of a dispensing and metering system according to a third exemplary embodiment of the present disclosure;

"FIGS. 4A-4C show the time sequence of dispensing of a stored substance to a fluid in a dispensing and metering system according to a further exemplary embodiment of the present disclosure;

"FIG. 5 shows diagrammatically a view from above of a separation element with a layer structure according to the present disclosure;

"FIG. 6 shows diagrammatically a view from above of a separation element composed of different materials in a mixed arrangement according to the present disclosure; and

"FIG. 7 shows diagrammatically a cartridge having a dispensing and metering system according to a further exemplary embodiment of the present disclosure."

For additional information on this patent application, see: Daub, Martina; Steigert, Juergen; Hoehl, Melanie. Dispensing and Metering System, in Particular of Substances in Microfluidic Systems, and Also Method and Cartridge Having the Dispensing and Metering System. Filed November 27, 2013 and posted June 5, 2014. Patent URL: http://appft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&u=%2Fnetahtml%2FPTO%2Fsearch-adv.html&r=5639&p=113&f=G&l=50&d=PG01&S1=20140529.PD.&OS=PD/20140529&RS=PD/20140529

Keywords for this news article include: Chemistry, Biochemical, Robert Bosch GmbH.

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Source: Life Science Weekly


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