System for operating a system for the integrated and automated analysis of DNA or protein

• US 10,073,107 B2
• Filed: 08/18/2015
• Issued: 09/11/2018
• 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): Dauner, Joseph G
• Application Number:
  US14/828,878
• Publication Number:
  US 20160047832A1
• Time in Patent Office: 1,120 Days
• Field of Search: None
• 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

A system for the integrated and automated analysis of DNA or protein, including a single-use cartridge, with an analysis device having a control device, and devices for capturing and processing signals, the control device carrying out a completely automatic process and evaluation of molecular diagnostic analysis via single-use cartridges (Lab-on-a-Chip). Controlling of an analysis process, which occurs in the cartridge, involves the subsequent displacement and thermostatization of liquids with a first device, and with a second device the signals which are obtained during the analysis are processed. 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. A system for the integrated an automated analysis of DNA or protein, comprising:

a cartridge to receive a sample to be analyzed, the cartridge containing a reagent for analysis of the sample;

a control device for controlling an analysis process, wherein the control device comprises;

a cartridge receptacle for receiving the cartridge;

means for moving a part of the cartridge receptacle upon insertion of the cartridge into the cartridge receptacle, such that the cartridge is correctly received in the cartridge receptacle;

a microcontroller for control and data acquisition; and

wherein the two parts of the cartridge receptacle are brought together as soon as the cartridge has been completely introduced in the cartridge receptacle,

wherein the control device comprises a thermostatic regulation device for carrying out at least one thermocycling process, wherein the thermostatic regulation device comprises two thermal coupling plates arranged so as to provide good thermal contact with the cartridge while avoiding thermal contact between the thermal coupling plates and the cartridge receptacle, and wherein the cartridge, in an inserted state, is situated between the thermal coupling plates and the thermal coupling plates are pressed against the cartridge such that the cartridge is held between the thermal coupling plates.

2. System according to claim 1, wherein the cartridge comprises a sample port, wherein the sample port is configured to enable the sample to be pipetted into the cartridge via the sample port.

3. System according to claim 1, wherein the cartridge is a single-use cartridge.

4. System according to claim 1, wherein the cartridge is in the form of a plastic card.

5. System according to claim 1, wherein the cartridge comprises a plurality of microfluidic channels.

6. System according to claim 5, wherein the control device comprises at least one valve arranged in communication with the microfluidic channels, wherein said valve is controlled by the microcontroller.

7. System according to claim 5, wherein the control device comprises means for identifying the filling of at least one of the channels.

8. System according to claim 7, wherein the means for identifying comprises at least one capacitive sensor.

9. System according to claim 8, wherein the at least one capacitive filling level sensor comprises plural capacitive filling level sensors that share a common capacitor plate.

10. System according to claim 1, wherein the cartridge comprises at least one chamber, wherein the control device comprises a device for closing off and opening the at least one chamber.

11. System according to claim 1, wherein the cartridge comprises a PCR chamber, in which a PCR of the sample is able to be carried out.

12. System according to claim 1, wherein the cartridge comprises a detection chamber, in which DNA of the sample can be detected.

13. System according to claim 1, wherein the system comprises an evaluation unit that is separate from the control device.

14. System according to claim 1, wherein the control device comprises a serial interface for connecting the microcontroller to a computing unit.

15. System according to claim 1, wherein the control device comprises a sensor for identifying the type of the cartridge in the cartridge receptacle.

16. System according to claim 1, further comprising a water reservoir to dilute the sample, to dissolve dry reagents stored in the cartridge and to carry out flushing operations in the control device.

17. System according to claim 1, further comprising a display for representing the analysis results.

18. System according to claim 1, wherein the control device comprises a power supply unit.

19. System according to claim 1, wherein at least one filling level sensor is provided that comprises an electrode above the cartridge and an electrode below the cartridge.

20. A system for the integrated and automated analysis of DNA or protein, comprising:

a cartridge to receive a sample to be analyzed, the cartridge containing a reagent for analysis of the sample;

a control device for controlling an analysis process, wherein the control device comprises;

a cartridge receptacle for receiving the cartridge with two parts;

a microcontroller for control and data acquisition; and

a chip module for detection of DNA or protein;

wherein as soon as the cartridge has been completely introduced the two parts are brought together and the cartridge is locked or clamped inbetween,

wherein the chip module is thermally coupled to a Peltier element,

wherein the Peltier element is connected to one of the parts of the cartridge receptacle, and

wherein the Peltier element and chip are biased against each other in a resilient fashion.

21. System according to claim 20, wherein the cartridge comprises a sample port, wherein the sample port is configured to enable the sample to be pipetted into the cartridge via the sample port.

22. System according to claim 20, wherein the cartridge is a single-use cartridge.

23. System according to claim 20, wherein the cartridge is in the form of a plastic card.

24. System according to claim 20, wherein the cartridge comprises a plurality of microfluidic channels.

25. System according to claim 24, wherein the control device comprises at least one valve arranged in communication with the microfluidic channels, wherein said valve is controlled by the microcontroller.

26. System according to claim 24, wherein the control device comprises means for identifying the filling of at least one of the channels.

27. System according to claim 26, wherein the means for identifying comprises at least one capacitive sensor.

28. System according to claim 27, wherein the at least one capacitive filling level sensor comprises plural capacitive filling level sensors that share a common capacitor plate.

29. System according to claim 20, wherein the cartridge comprises at least one chamber, wherein the control device comprises a device for closing off and opening the at least one chamber.

30. System according to claim 20, wherein the cartridge comprises a PCR chamber, in which a PCR of the sample is able to be carried out.

31. System according to claim 20, wherein the cartridge comprises a detection chamber, in which DNA of the sample can be detected.

32. System according to claim 20, wherein the system comprises an evaluation unit that is separate from the control device.

33. System according to claim 20, wherein the control device comprises a serial interface for connecting the microcontroller to a computing unit.

34. System according to claim 20, wherein the control device comprises a sensor for identifying the type of the cartridge in the cartridge receptacle.

35. System according to claim 20, further comprising a water reservoir to dilute the sample, to dissolve dry reagents stored in the cartridge and to carry out flushing operations in the control device.

36. System according to claim 20, further comprising a display for representing the analysis results.

37. System according to claim 20, wherein the control device comprises a power supply unit.

38. System according to claim 20, wherein at least one filling level sensor is provided that comprises an electrode above the cartridge and an electrode below the cartridge.