System for the integrated and automated analysis of DNA or protein and method for operating said type of system

• US 9,110,044 B2
• Filed: 05/22/2006
• Issued: 08/18/2015
• Est. Priority Date: 05/25/2005
• Status: Active Grant

• Current Assignee: Boehringer Ingelheim Vetmedica GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Original Assignee: Boehringer Ingelheim Vetmedica GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Inventors: Gumbrecht, Walter, Paulicka, Peter
• Primary Examiner(s): Nguyen, Dave
• Assistant Examiner(s): Dauner, Joseph G
• Application Number:
  US11/920,978
• Publication Number:
  US 20090298059A1
• Time in Patent Office: 3,375 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/0668 Trapping microscopic beads
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2200/143 Quality control, feedback systems
• CPC Class Codes: B01L 2300/023 Sending and receiving of information, e.g. using bluetooth
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• CPC Class Codes: B01L 2300/1877 using chemical reactions
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/502723 characterised by venting arrangements
• CPC Class Codes: B01L 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 3/502761 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: B01L 7/52 with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: B01L 9/527 for microfluidic devices, e.g. used for lab-on-a-chip
• CPC Class Codes: C12Q 1/686 Polymerase chain reaction [PCR]
• CPC Class Codes: G01N 2035/00019 cassette structures
• CPC Class Codes: G01N 2035/00346 Heating or cooling arrangements
• CPC Class Codes: G01N 2035/00376 Conductive heating, e.g. heated plates
• CPC Class Codes: G01N 2035/00841 : results of the analyses
• CPC Class Codes: G01N 2035/1034 : Transferring microquantities of liquid
• CPC Class Codes: G01N 35/00009 : provided with a sample supporting tape, e.g. with absorbent zones
• CPC Class Codes: G01N 35/00584 : Control arrangements for automatic analysers
• CPC Class Codes: G01N 35/00732 : Identification of carriers, materials or components in automatic analysers
• CPC Class Codes: G01N 35/00871 : Communications between instruments or with remote terminals
• CPC Class Codes: G01N 35/08 : using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
• CPC Class Codes: G01N 35/1002 : Reagent dispensers

Abstract

An embodiment of the present invention relates to a system for the integrated and automated analysis of DNA or protein, including a single-use cartridge, an analysis device comprising a control device, and devices for capturing and processing signals. An embodiment of the present invention relates, in particular, to the control device for carrying out a completely automatic process and evaluation of molecular diagnostic analysis via single-use cartridges (Lab-on-a-Chip). The first devices are provided for controlling an analysis process which occurs in the cartridge, subsequently the displacement and the thermostatisation of liquids, and the second devices are provided for processing the signals which are obtained during the analysis. The first and the second devices are synchronized in such a manner that the analysis process of the sample can be carried out in a totally integrated manner thus producing an immediate result.

Claims

1. Biochip analysis device, comprising:

a cartridge in the form of a plastic card which contains a system of microfluidic channels that form a reservoir that contains a reaction substance, a sample chamber and flow channels, a fluid input covered by a pierceable septum and a cover film overlying the system of microfluidic channels,

a control device having a cartridge receptacle for receiving, locking, unlocking and releasing the cartridge, the control device comprising;

a power supply connected to the cartridge receptacle,

a plurality of first sensors adapted for identifying whether or not a cartridge located in the cartridge receptacle is a correct cartridge and correctly located therein,

a means for positioning a cartridge inserted into the cartridge receptacle,

a plurality of second sensors which are adapted to emit an externally measurable signal representative of information about an analyte in a cartridge located in the cartridge receptacle,

fill level sensor means for monitoring of the flow of fluid in the cartridge,

a microcontroller adapted for control and data acquisition, and having means for transmitting data to an external computer, and

a pump controlled by the microcontroller and adapted to direct a flow of liquid into and through a cartridge located in the cartridge receptacle,

wherein the cartridge receptacle is comprised of upper and lower parts that are movable apart for insertion of a cartridge and together for locking an inserted cartridge in the cartridge receptacle, and

wherein a thermostatic regulation device is provided that has thermal coupling plates at positions adapted for transferring heat to a cartridge in the cartridge receptacle, a one of the coupling plates on a side facing the cover of an inserted cartridge having a cutout which enables bulging of the cover film in the event of excess pressure within the cartridge.

2. The biochip analysis device as claimed in claim 1, wherein interfaces for fluidics and electronics are present between the cartridge and the control device.

3. The biochip analysis device as claimed in claim 2, wherein the control device comprises at least one of at least one serial and one wireless interface via which at least one of the signals and at least partly processed signals are in communication.

4. The biochip analysis device as claimed in claim 1, further comprising sensors configured to identify a correct orientation of the cartridge in the cartridge receptacle.

5. The biochip analysis device as claimed in claim 4, further comprising sensors configured to identify a correct type of the cartridge in the cartridge receptacle.

6. The biochip analysis device as claimed in claim 1, wherein a water reservoir configured to dilute the sample, to dissolve dry reagents stored in the cartridge and to carry out flushing operations in the control device is provided.

7. The biochip analysis device as claimed in claim 6, further comprising a filter to ventilate the water reservoir when water is drawn.

8. The biochip analysis device as claimed in claim 1, further comprising a hollow needle arranged for piercing the pierceable septum.

9. The biochip analysis device as claimed in claim 1, further comprising capacitive sensors identifying the filling of channels on the cartridge.

10. The biochip analysis device as claimed in claim 9, wherein the capacitive sensors includes electrodes, wherein the electrodes are arranged in such a way that, when the cartridge is introduced into the control device, one of the electrodes is situated above the cartridge and one of the electrodes is situated below the cartridge.

11. The biochip analysis device as claimed in claim 1, further comprising a closing/opening device configured to close off and open chambers in the cartridge.

12. The biochip device as claimed in claim 11, wherein the closing/opening device configured to close off and open the chambers are embodied as movable plungers.

13. The biochip analysis device as claimed in claim 1, further comprising a magnetic bead collector configured to capture magnetic beads, wherein the magnetic bead collector is combined into a unit with the thermostatic regulation device.

14. The biochip analysis device as claimed in claim 13, further comprising a contact pressure device configured to a defined contact pressure between thermostatic regulation modules and the cartridge.

15. The biochip analysis device as claimed in claim 1, further comprising an electrical contact device configured to make electrical contact with an electrical chip module.

16. The biochip analysis device as claimed in claim 15, wherein the electrical chip module includes a thermostatic regulation unit.

17. The biochip analysis device as claimed in claim 1, wherein the cartridge is a single-use cartridge.

18. The biochip analysis device as claimed in claim 1, wherein the cartridge includes a PCR chamber, and a magnetic core is located directly at a surface of the PCR chamber when the cartridge is inserted in the cartridge receptacle.