Dead volume reduction and method therefor
A method for minimizing the dead volume in a vial presenting a liquid for aspiration is provided. The method comprises, after determining that the liquid volume indicated to be available in the vial is not sufficient for a further aspiration step, moving downward in direction towards the bottom of the vial by means of a pipetting arm presenting a pipetting tip and along the z-axis of the pipetting arm until the pipetting arm comes to a stop in a first stop position. Then, the actual available liquid volume is calculated based on said first stop position. In case the calculated actual available liquid volume is sufficient, a further aspiration step can be executed. Furthermore, a liquid handling system for minimizing dead volume, a computer-implemented method for controlling a pipetting arm of such a liquid handling system, and the use of a hysteresis determination method for minimizing dead volume are provided.
1 . A method for minimizing the dead volume (Vd) in a vial ( 10 ) presenting a liquid (L) for aspiration, the method comprising:
determining whether the liquid volume (Vi) indicated to be available in the vial ( 10 ) is sufficient for a further aspiration step;
if not, moving downward in direction towards the bottom of the vial by means of a pipetting arm ( 20 ) presenting a pipetting tip ( 21 ) and along the z-axis of the pipetting arm ( 20 ) until the pipetting arm ( 20 ) comes to a stop in a first stop position (S 1 z );
storing the first stop position (S 1 z ) of the pipetting arm ( 20 ) or correcting the first stop position (S 1 z ) by a predetermined safety measure (Ds) and storing this first safety corrected stop position (S 1 SCz) of the pipetting arm ( 20 ); and further
calculating the actual available liquid volume (Va) based on the liquid level known from determining whether the liquid volume (Vi) indicated to be available in the vial ( 10 ) is sufficient for a further aspiration step and the first stop position (S 1 z ) or calculating the actual safety corrected available liquid volume (VaSC) based on the liquid level determining whether the liquid volume (Vi) indicated to be available in the vial ( 10 ) is sufficient for a further aspiration step and the first safety corrected stop position (S 1 SCz); and/or
detecting the liquid level (LL) of the liquid (L) provided in the vial ( 10 ) and calculating the actual available liquid volume (Va) based on the detected liquid level (LL) and the first stop position (S 1 z ) or calculating the actual safety corrected available liquid volume (VaSC) based on the detected liquid level (LL) and the first safety corrected stop position (S 1 SCz); and wherein the method further comprises:
conductively detecting a conductive surface ( 30 ) by means of the pipetting arm ( 20 ) presenting the pipetting tip ( 21 );
storing the position of the pipetting arm ( 20 ) when conductively detecting the conductive surface ( 30 ) as first position (P 1 z );
moving the pipetting arm ( 20 ) towards the conductive surface ( 30 ) and along the z-axis of the pipetting arm ( 20 ) until the pipetting arm ( 20 ) applies a predetermined force and therefore comes to a stop;
storing the position when the pipetting arm ( 20 ) comes to a stop as second position (P 2 z );
calculating the hysteresis (Hz) by determining the height difference between the first position (P 1 z ) and the second position (P 2 z ).
2 . The method according to claim 1 , further comprising:
executing a further aspiration step when the calculated actual available liquid volume (Va) is sufficient; or
executing a further aspiration step when the calculated actual safety corrected available liquid volume (VaSC) is sufficient; or
not executing a further aspiration step when the calculated actual available liquid volume (Va) is not sufficient; or
not executing a further aspiration step when the calculated actual safety corrected available liquid volume (VaSC) is not sufficient.
3 . The method according to claim 1 , wherein the step of determining whether the liquid volume (vi) available in the vial is sufficient for a further aspiration step comprises:
detecting the liquid level (LL) of a liquid (L) provided in the vial ( 10 ) for a first time;
calculating the indicated liquid volume (Vi) in the vial.
4 . The method according to claim 1 , wherein the step of detecting the liquid level (LL) of a liquid (L) provided in the vial ( 10 ) is executed by conductive liquid level detection (cLLD) and/or pressure based LLD (pLLD).
5 . The method according to claim 3 , wherein the step of detecting the liquid level (LL) of a liquid (L) provided in the vial ( 10 ) for a first time is executed by conductive liquid level detection (cLLD) and/or pressure based LLD (pLLD).
6 . The method according to claim 1 , wherein a force at which the pipetting arm ( 20 ) comes to a stop in the first stop position (S 1 z ) is predetermined.
7 . The method according to claim 1 , wherein the calculated hysteresis (Hz) is used for correcting:
the actual height of the liquid level (Ha); and/or
the calculated actual available liquid volume (Va); and/or
the actual safety corrected height of the liquid level (HaSC); and/or
the calculated actual safety corrected available liquid volume (VaSC).
8 . The method according to claim 6 , wherein the predetermined force at which the pipetting arm ( 20 ) comes to a stop in the first stop position (S 1 z ) is identical to the predetermined force at which the pipetting arm ( 20 ) comes to a stop in the second position (P 2 z ).
9 . A liquid handling system ( 1 ) for minimizing the dead volume (Vd) in a vial ( 10 ) presenting a liquid (L) for aspiration, the automated liquid handling system comprising:
at least one pipetting arm ( 20 ) connectable to a pipetting tip ( 21 ) and operatively connected to a pressure source for aspirating and dispensing liquids;
a workbench ( 5 ) for supporting vials ( 10 ) for presenting a liquid (L);
means for liquid level detection;
an operational unit ( 40 ) configured to perform the method according to claim 1 .
10 . The liquid handling system ( 1 ) according to claim 9 , further comprising a conductive surface ( 30 ) accessible by the at least one pipetting arm ( 20 ) connected to a pipetting tip ( 21 ).
11 . A computer-implemented method for controlling the at least one pipetting arm ( 20 ) of the liquid handling system ( 1 ) according to claim 9 , the method comprising:
moving the pipetting arm ( 20 ) presenting a pipetting tip ( 21 ) downwards along the z-axis of the pipetting arm ( 20 ) towards the bottom of a vial ( 10 ) presented on the workbench ( 5 ) of the liquid handling system ( 1 ) until the pipetting arm ( 20 ) comes to the stop in the first stop position (S 1 z ).
12 . A computer-implemented method for controlling the at least one pipetting arm ( 20 ) of the liquid handling system ( 1 ) according to claim 9 , the method comprising:
conductively detecting a conductive surface ( 30 ) by means of the pipetting arm ( 20 ) presenting the pipetting tip ( 21 );
moving the pipetting arm ( 20 ) towards the conductive surface ( 30 ) and along the z-axis of the pipetting arm ( 20 ) until the pipetting arm ( 20 ) applies a predetermined force and therefore comes to a stop.
13 . A method for minimizing the dead volume (Vd) in a vial ( 10 ) presenting a liquid (L) for aspiration utilizing a hysteresis determination method, the method comprising:
conductively detecting a conductive surface ( 30 ) by means of pipetting arm ( 20 ) presenting a pipetting tip ( 21 );
storing the position of the pipetting arm ( 20 ) when conductively detecting the conductive surface ( 30 ) as first position (P 1 z );
moving the pipetting arm ( 20 ) towards the conductive surface ( 30 ) and along the z-axis of the pipetting arm ( 20 ) until the pipetting arm ( 20 ) applies a predetermined force and therefore comes to a stop;
storing the position when the pipetting arm ( 20 ) comes to a stop as second position (P 2 z );
calculating the hysteresis (Hz) by determining the height difference between the first position (P 1 z ) and the second position (P 2 z ).
14 . The method according to claim 1 , wherein the conductive surface ( 30 ) is a non-anodized aluminum surface.
15 . The method according to claim 2 , wherein
the step of not executing a further aspiration step when the calculated actual available liquid volume (Va) is not sufficient, or
the step of not executing a further aspiration step when the calculated actual safety corrected available liquid volume (VaSC) is not sufficient, is combined with generating an error message.
16 . The method according to claim 3 , wherein the step of calculating the indicated liquid volume (Vi) in the vial is based on the indicated height (Hi) of the liquid level (LL) or based on a predetermined inner bottom position of the vial (Zp).
17 . The method according to claim 7 , wherein the actual height of the liquid level (Ha); and/or the calculated actual available liquid volume (Va); and/or the actual safety corrected height of the liquid level (HaSC); and/or the calculated actual safety corrected available liquid volume (VaSC) are corrected by correcting the first stop position (S 1 z ) or by correcting the first safety corrected stop position (S 1 SCz).
18 . The liquid handling system ( 1 ) according to claim 10 , wherein the conductive surface ( 30 ) is formed integrally with the liquid handling system or is not formed integrally with the liquid handling system.
19 . The liquid handling system ( 1 ) according to claim 18 , wherein the conductive surface ( 30 ) is at least one of the following:
positioned on the workbench ( 5 );
a metal block;
a non-anodized aluminum surface.
20 . The liquid handling system ( 1 ) according to claim 9 , wherein the operational unit ( 40 ) is a computer or processor.
21 . The computer-implemented method according to claim 11 , wherein a force at which the pipetting arm ( 20 ) comes to a stop in the first stop position (S 1 z ) is predetermined.
22 . The computer-implemented method according to claim 12 , wherein the conductive surface ( 30 ) is a non-anodized aluminum surface.
23 . The method according to claim 13 , wherein the conductive surface ( 30 ) is a non-anodized aluminum surface.
24 . A computer-implemented method for controlling an at least one pipetting arm ( 20 ) of a liquid handling system ( 1 ) for minimizing the dead volume (Vd) in a vial ( 10 ) presenting a liquid (L) for aspiration, the automated liquid handling system comprising:
at least one pipetting arm ( 20 ) connectable to a pipetting tip ( 21 ) and operatively connected to a pressure source for aspirating and dispensing liquids;
a workbench ( 5 ) for supporting vials ( 10 ) for presenting a liquid (L);
means for liquid level detection;
an operational unit ( 40 ) configured to perform a method for minimizing the dead volume (Vd) in the vial ( 10 ) presenting the liquid (L) for aspiration,
the method comprising:
determining whether the liquid volume (Vi) indicated to be available in the vial ( 10 ) is sufficient for a further aspiration step;
if not, moving downward in direction towards the bottom of the vial by means of the pipetting arm ( 20 ) presenting a pipetting tip ( 21 ) and along the z-axis of the pipetting arm ( 20 ) until the pipetting arm ( 20 ) comes to a stop in a first stop position (S 1 z );
storing the first stop position (S 1 z ) of the pipetting arm ( 20 ) or correcting the first stop position (S 1 z ) by a predetermined safety measure (Ds) and storing this first safety corrected stop position (S 1 SCz) of the pipetting arm ( 20 ); and further
calculating the actual available liquid volume (Va) based on the liquid level known from determining whether the liquid volume (Vi) indicated to be available in the vial ( 10 ) is sufficient for a further aspiration step and the first stop position (S 1 z ) or calculating the actual safety corrected available liquid volume (VaSC) based on the liquid level determining whether the liquid volume (Vi) indicated to be available in the vial ( 10 ) is sufficient for a further aspiration step and the first safety corrected stop position (S 1 SCz); and/or
detecting the liquid level (LL) of the liquid (L) provided in the vial ( 10 ) and calculating the actual available liquid volume (Va) based on the detected liquid level (LL) and the first stop position (S 1 z ) or calculating the actual safety corrected available liquid volume (VaSC) based on the detected liquid level (LL) and the first safety corrected stop position (S 1 SCz),
the method further comprising:
conductively detecting a non-anodized aluminum surface by means of the pipetting arm ( 20 ) presenting the pipetting tip ( 21 );
moving the pipetting arm ( 20 ) towards the non-anodized aluminum surface and along the z-axis of the pipetting arm ( 20 ) until the pipetting arm ( 20 ) applies a predetermined force and therefore comes to a stop.