# US 2014/0193826 A1 · Sample handling system with dosing device and thermal cycler

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- Number: US 2014/0193826 A1
- Document ID: US20140193826A1
- Status: Published application
- Kind: A1
- Application number: 14/150,041
- Filed: 2014-01-08
- Published: 2014-07-10
- Earliest claimed: 2013-01-09
- Assignees: Hamilton Bonaduz AG
- Applicants: Hamilton Bonaduz AG
- Inventors: Martin GAJEWSKI; Mario ARANGIO
- Web page: https://patentgrep.com/patent/US20140193826A1

## CPC

- C12Q 1/686: Polymerase chain reaction [PCR]
- G01N 35/0099: {comprising robots or similar manipulators (robots per se B25J)}
- G01N 35/028: {having reaction cells in the form of microtitration plates}
- G01N 35/10: Devices for transferring samples {or any liquids} to, in, or from, the analysis apparatus, e.g. suction devices, injection devices {(G01N35/0099 takes precedence)}
- G01N 2035/00287: {movable lid/cover for sample or reaction tubes}
- G01N 2035/00346: {Heating or cooling arrangements}
- G01N 2035/1051: {for transporting containers, e.g. retained by friction}
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The invention concerns a sample handling system and a process for the handling of chemical or biological samples, particularly body fluids such as blood, saliva, secretions, etc. or tissue samples, and more specifically for the processing of samples for DNA analysis by means of PCR, comprising a dosing device with a receiving plate (12), with the receiving plate (12) being configured in an essentially horizontal position in a plane defined by a first and a second axis (X, Y); having at least one working arm (14, 16, 18) that is movable in the direction of the first axis (X) relative to the receiving plate (12), preferably along a first edge (13) of the receiving plate (12), and wherein the working arm (14, 16, 18) extends along the second axis (Y) above the receiving plate (12), at least one pipetting mechanism (30) that is movable in the direction of the second axis (Y) is mounted on the working arm (14, 16, 18), the pipetting mechanism (30) comprises at least one pipetting channel (32) that is movable in the direction of a third axis (Z) orthogonal to the direction of the first and second axes (X, Y) and has a pipette tip (33) mounted or mountable thereon, and said pipetting mechanism (30) is configured so as to dispense or aspirate liquid into or out of a sample vessel; and at least one thermal cycler (50, 52) provided in the area of the receiving plate (12). According to the invention, the thermal cycler (50, 52) should be configured on the receiving plate (12) in such a way that the pipetting mechanism (30) is movable in a position above the sample vessels in the thermal cycler (50, 52), making a pipetting step possible. Opening/closing of a closing device (54) of the thermal cycler takes place in accordance with the steps of a PCR process, and pipetting of components into sample vessels in the thermal cycler takes place in accordance with the setting of the closing device (54).

## Claims

### Claim 1

Sample handling system for the handling of chemical or biological samples, particularly body fluids such as blood, saliva, secretions, etc. or tissue samples, and more specifically for the processing of samples for DNA analysis by means of PCR, comprising
a dosing device
with a receiving plate (12), wherein the receiving plate (12) is configured in an essentially horizontal position in a plane defined by a first and a second axis (X, Y);
having at least one working arm (14, 16, 18) that is movable in the direction of the first axis (X) relative to the receiving plate (12), preferably along a first edge (13) of the receiving plate (12), and wherein the working arm (14, 16, 18) extends in the direction of the second axis (Y) above the receiving plate (12),
wherein at least one pipetting mechanism (30) that is movable in the direction of the second axis (Y) is mounted on the working arm (14, 16, 18), the pipetting mechanism (30) comprises at least one pipetting channel (32) that is movable in the direction of a third axis (Z) orthogonal to the direction of the first and second axes (X, Y) and has a pipette tip (33) mounted or mountable thereon, and the pipetting mechanism (30) is configured so as to dispense or aspirate liquid into or out of a sample vessel; and
at least one thermal cycler (50, 52) that is provided in the area of the receiving plate (12),
characterized in that the thermal cycler (50, 52) is configured on the receiving plate (12) in such a way that the pipetting mechanism (30) is movable in a position above the sample vessels in the thermal cycler (50, 52) in a setting that allows a pipetting step to be carried out.

### Claim 2 (depends on 1)

Sample handling system according to claim 1, characterized by also comprising a control mechanism that is configured so as to activate or control functions of the dosing device such as a movement in the directions of the three axes and/or aspiration or dispensing of liquid by means of the pipetting mechanism (30) and functions of the thermal cycler (50, 52) such as carrying out cycles in a PCR process.

### Claim 3 (depends on 1)

Sample handling system according to claim 1, characterized in that the thermal cycler (50, 52) is mounted on the receiving plate (12), wherein a highest point (58) of the thermal cycler is located below a maximum possible interval (HP) between a lower end of at least one pipette tip (33) on the receiving plate (12), and wherein this interval (HP) makes it possible for the pipetting mechanism (30) or the pipetting channel (32) to move in the direction of a third axis (Z).

### Claim 4 (depends on 1)

Sample handling system according to claim 1, characterized in that the thermal cycler (50′) is mounted in a notch made in the receiving plate (12) in such a manner that a lower surface (51′) of the thermal cycler (50′) is located below the receiving plate (12), wherein a highest point (58) of the thermal cycler (50′) is located below a maximum possible interval (HP) between a lower end of at least one pipette tip (33) and the receiving plate (12), with the interval (HP) making it possible for the pipetting mechanism (30) or pipetting channels (32) to move in the direction of a third axis (Z).

### Claim 5 (depends on 3)

Sample handling system according to claim 3, characterized in that the maximum interval (HP) between the lower end of at least one pipette tip (33) and the receiving plate (12) is approximately 100 mm to 180 mm, and preferably approximately 125 mm to 150 mm.

### Claim 6 (depends on 1)

Sample handling system according to claim 1, characterized in that the thermal cycler (50, 52) is provided with a lid-like closing device (54) for covering the sample vessels inside the thermal cycler (50, 52), wherein the closing device (54) is movable relative to the thermal cycler (50, 52) in a direction that is essentially parallel to the receiving plate (12) between an open setting in which the interior (56) of the thermal cycler (50) is freely accessible and a closed setting in which the interior (56) of the thermal cycler (54) is covered.

### Claim 7 (depends on 6)

Sample handling system according to claim 6, characterized in that the control mechanism is configured in such a manner that the closing device (54) of the thermal cycler (50, 52) is moved into its open or closed setting depending on the position of the pipetting mechanism (30) relative to the thermal cycler (50, 52), preferably such that the closing device (54) is moved to its open setting when a step of pipetting into the sample vessels inside the thermal cycler (50, 52) is carried out by means of the pipetting mechanism (30) and such that the closing device (54) is moved to its closed setting after the step of pipetting into the sample vessels inside the thermal cycler (50, 52) is completed.

### Claim 8 (depends on 1)

Sample handling system according to claim 1, further comprising a gripping mechanism that is movable in the directions of the first, second, and third axes relative to the receiving plate (12) is activated by the control mechanism, and is configured so as to grip the sample vessel carrier and transport it to desired positions on the receiving plate (12).

### Claim 9 (depends on 8)

Sample handling system according to claim 8, characterized in that the gripping mechanism is configured so as to displace sample vessels inside or remove sample vessels from the thermal cycler (50, 52).

### Claim 10 (depends on 8)

Sample handling system according to claim 8, characterized in that the gripping mechanism is placed on the working arm (14, 16, 18) or provided on an additional movable working arm that is movable relative to the receiving plate (12).

### Claim 11 (depends on 1)

Process for the control of a sample handling system according to claim 1 by means of its accompanying control mechanism, comprising the following steps:
opening of the closing device (54) of a first thermal cycler (50);
displacement of a sample vessel carrier containing sample vessels inside the first thermal cycler (50) by means of the gripping mechanism, with the sample vessels being filled with sample liquid or unfilled;
if applicable, filling of the sample vessels with sample liquid to be analysed by means of the pipetting mechanism (30);
preferably, filling of the sample vessels with further components required for analysis, such as a primer, polymerase, water, etc. by means of the pipetting mechanism (30);
conducting a PCR process, wherein the closing device (54) of the first thermal cycler (50) is opened or closed depending on the steps of the PCR process to be conducted, and wherein, depending on the setting of the closing device (54), additional components are dispensed by the pipetting mechanism (30) to the sample vessels inside the first thermal cycler (50).

### Claim 12 (depends on 11)

Process according to claim 11, further comprising the preferably automated movement or removal of a sealing element that seals the sample vessels, such as a sealing mat, etc. on the sample vessel carrier, depending on the PCR process and the setting of the closing device (54).

### Claim 13 (depends on 11)

Process according to claim 11, wherein after completion of a specified step of the PCR process, the closing device (54) of the first thermal cycler (50) is opened, the sealing element preferably placed on the sample vessels is removed, and processed sample liquid is aspirated from the sample vessels by means of the pipetting mechanism (30) and dispensed into additional, preferably empty sample vessels outside the first thermal cycler (50), with the other sample vessels being located in a sample vessel carrier that is preferably placed in a second, preferably adjacent thermal cycler (52) or on the receiving plate (12).

### Claim 14 (depends on 13)

Process according to claim 13, further comprising the dispensing of a further component in sample vessels contained inside the first and/or second thermal cycler (50) by means of the pipetting mechanism, with this pipetting step being followed by placement of the sealing elements on the sample vessels, closing of the closing device (54) of the first and/or second thermal cycler (50), and carrying out of further steps of the PCR process.