Apparatus and method for dispensing or aspirating fluid

Abstract

A method dispenses and/or aspirates a predetermined volume of fluid from a chamber. The chamber includes a lower portion containing fluid and an upper portion containing gas. The method includes measuring an initial pressure in the upper portion and introducing or evacuating a known quantity of gas into or out of the upper portion. The volume of gas in the upper portion is determined based on the volume of gas introduced or evacuated from the upper portion and a measured change in pressure in the upper portion. An upper portion target pressure that will dispense or aspirate a predetermined volume of fluid is determined. A controllable valve is opened while the pressure in the upper portion of the chamber is monitored. Once the target pressure is reached, the predetermined volume of fluid has been dispensed or aspirated, and the controllable valve is then closed.

Claims

1. A method for dispensing and/or aspirating a fluid, comprising: providing an apparatus and a single chamber of unknown internal volume connected thereto, the apparatus being configured to dispense and/or aspirate a predetermined volume V of fluid from the single chamber, the single chamber comprising a lower portion and an upper portion entirely communicating with each other, the lower portion configured to contain said fluid, the upper portion configured to contain a gas, the apparatus comprising: a controllable valve configured to be in fluid communication with the lower portion of the chamber; a pressure sensor configured to be in gaseous communication with the upper portion of the chamber; a pump configured to be in gaseous communication between a source of gas and the upper portion of the chamber; and a controller in operative connection with the controllable valve, the pressure sensor, and the pump, wherein the controller is configured to determine the predetermined volume V of fluid to be dispensed or aspired from the chamber based on gas pressure measurements from the pressure sensor in the upper portion of the chamber and to control operation of the pump and operation of the controllable valve based on said pressure measurements from the pressure sensor, such that the upper portion of the chamber is in fluid communication with the pump and such that the lower portion of the chamber is in fluid communication with the controllable valve; providing fluid in the lower portion of the chamber and a volume V.sub.1 of gas in the upper portion of the chamber; measuring, by the pressure sensor, an initial pressure P.sub.0 in the upper portion of the chamber after providing the fluid and the volume V.sub.1 of gas; introducing or evacuating a known quantity of gas into or out of the upper portion of the chamber respectively after measuring the initial pressure P.sub.0; measuring, by the pressure sensor, a first pressure P.sub.1 in the upper portion of the chamber by means of the pressure sensor after introducing or evacuating the known quantity of gas; determining the volume V.sub.1 of gas in the upper portion of the chamber based on said known quantity of gas, said initial pressure P.sub.0, and said first pressure P.sub.1; said volume V.sub.1 of gas being determined by the following equation: $V_1=\frac{\left(n_1-n_0\right)\mathrm{RT}}{\left(P_1-P_0\right)}$ wherein (n.sub.1n.sub.0) is the number of moles of gas displaced by the pump, R is the ideal gas constant, and T is a temperature measured by a temperature sensor; followed by determining a target pressure P.sub.2 of the upper portion of the chamber, said target pressure being calculated so as to dispense or to aspirate said predetermined volume V of fluid; followed by opening said controllable valve to dispense fluid while monitoring the pressure in the upper portion of the chamber by means of the pressure sensor; and followed by closing said controllable valve once said target pressure P.sub.2 is reached and after the predetermined volume V of fluid is dispensed or aspirated.

2. A method according to claim 1, wherein said known quantity of gas is a predetermined number n of moles of gas.

3. A method according to claim 1, wherein said first pressure P.sub.1 is predetermined, and said known quantity of gas is a number n of moles of gas measured so as to attain said predetermined second pressure.

4. A method according to claim 1, wherein (n.sub.1n.sub.0) is determined by the equation:
(n.sub.1n.sub.0)=f.sub.n(P.sub.1)s.sub.0 wherein f.sub.n(P.sub.1) is a predetermined calibration curve of the pump, and s.sub.0 is a function of the operation of the pump determined by the controller.

5. A method according to claim 4, wherein the pump is a reciprocating pump and s.sub.0 is the number of strokes of the pump.

6. A method according to claim 1, wherein the target pressure P.sub.2 is determined by the equation: $P_2=\frac{V_1^k}{{\left(V_1+V\right)}^k}{P}_1$ where V.sub.1 is the gas volume within the containment before dispensing, V the dispensed or aspirated liquid predetermined volume, k the polytropic exponent, and P.sub.1 is the pressure in the chamber before dispensing or aspirating.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) Further details of the invention will become more apparent with reference to the following description and the accompanying figures, in which:

(2) FIG. 1 represents schematically an apparatus according to the invention;

(3) FIG. 2 represents a flow diagram of a method according to the invention;

(4) FIG. 3 represents schematically a graph of various parameters of the gas in the chamber and how they change with time when carrying out the method;

(5) FIG. 4 represents schematically a variant of an apparatus according to the invention; and

(6) FIG. 5 represents schematically a further variant of an apparatus according to the invention.

DETAILED DESCRIPTION

(7) In the following figures, thick lines indicate fluid connections, dashed lines indicate electrical connections, and chain lines group components in functional groups. Similar reference signs indicate the same or similar components.

(8) FIG. 1 illustrates schematically a generic embodiment of an apparatus 1 according to the invention, fully assembled with a chamber 3, ready for use. The chain line defines the components considered as being part of the apparatus 1, since the apparatus 1 can be used with any convenient chamber 3, which may for instance simply be a lab flask. In such a case, the apparatus of the invention can advantageously be arranged in a container represented by the chain line, said container being in an example a cap for a said lab flask. Alternatively, apparatus 1 may also comprise an integrated chamber 3. In the unassembled state, the various components are simply arranged to be connected in fluid communication with the chamber 3 according to the illustrated arrangement.

(9) Chamber 3 for holding fluid 5, which can be a liquid, a gel, a solution, a suspension, or similar. As such, chamber 3 serves as a reservoir for said fluid 5. Chamber 3 is arbitrarily divided into a lower portion 3a, in which an initial volume V.sub.0 of fluid 5 is situated or, in the case in which no fluid is present, is destined to be situated, and an upper portion 3b, in which gas 7 such as air, nitrogen, argon, oxygen, carbon dioxide, or any other suitable gas 7 can be situated. The exact choice of gas 7 used depends on the nature of the fluid 5, in particular its reactivity, susceptibility to oxidation, biological contamination, and so on. Upper and lower are defined with respect to gravity in the operational orientation of the chamber 3. Chamber 3 should be constructed of a material which is sufficiently stiff that the changes in pressure resulting from operation of the apparatus substantially do not change the shape of the chamber 3, and thus expansion or contraction of the chamber do not need to be taken into account when calculating the quantity of fluid dispensed of aspirated.

(10) A pump 9 is arranged in fluid communication, more specifically in gaseous communication, with the upper portion 3b of chamber 3 and with a source of gas 11 via a suitable conduit 10 such as a tube. Source of gas 11 may simply be an air inlet, or may be a cylinder containing another gas in the case in which the fluid 5 is incompatible with air for chemical or biological reasons. Pump 9 may be bidirectional, permitting both dispensing and aspirating fluid 5, or unidirectional, which in the illustrated embodiment permits one or the other of aspirating or dispensing fluid 5. A variant permitting both aspiration and dispensing with a unidirectional pump is described below in reference to FIG. 5.

(11) Pump 9 is ideally a positive displacement pump, i.e. a pump which displaces a known, constant volume of material for a given input. Such pumps can be reciprocating or rotary, and the skilled person is aware of a large variety of such pumps. Alternatively, pump 9 may be velocity pump combined with a flowmeter (not illustrated) in series with the pump so as to be able to determine the volume, and hence the quantity in moles, of gas pumped.

(12) Moving now to the lower portion 3a of chamber 3, lower portion 3a is in fluid communication with a controllable valve 13 via a suitable conduit 12, the controllable valve being in fluid communication with a nozzle 15. Nozzle 15 is thus in selective fluid communication with the lower portion 3a of chamber 13, controllable valve 13 serving to selectively connect the nozzle 15 to the lower portion 3a of chamber 3.

(13) A pressure sensor 17 is arranged in fluid communication, more specifically in gaseous communication, with the chamber 3, particularly the upper portion 3b thereof, so as to measure the pressure therein. As illustrated, pressure sensor 17 is directly connected to upper portion 3b of chamber 3, as would usually be the case in which the chamber 3 is integral to the apparatus; however it can equally be arranged inside chamber 3 or mounted in or connected to conduit 10 as is the case in the variants of FIGS. 4 and 5. In the case of using a standard laboratory flask or other convenient vessel as chamber 3, the pressure sensor can be attached to the inside of the cap of the flask so as to be situated inside the flask. This is particularly convenient in the case in which the flasks need to be changed.

(14) Optional temperature sensor 19 likewise is arranged so as to measure the temperature of the gas 7 in the chamber 3. This can be important for non-adiabatic and non-isothermic changes of condition.

(15) Finally, controller 21 is operatively connected with the following other components of the apparatus 1: pump 9 so as to control its operation and, if applicable, to count rotations, strokes, or other parameters of its operation; pressure sensor 17 so as to measure pressure in the upper portion 3b of chamber 3; temperature sensor 19 so as to measure temperature in the upper portion 3b of chamber 3; controllable valve 13, so as to control its opening and closing so as to dispense or aspirate, as desired, a quantity V of fluid 5.

(16) FIG. 2 illustrates a flow diagram of a method for dispensing or aspirating a predetermined volume of fluid according to the invention, and FIG. 3 represents volume V, pressure P and molarity n curves for the gas 7 in the chamber 3 during the measurement phases of the method when used for dispensing. In the case of aspiration, the various curves will simply have the opposite slopes, while the principle of operation remains the same.

(17) Firstly, in step 101 an apparatus 1 according to the invention is provided. In step 102, fluid 5 is provided in the chamber 3. If the gas 7 is air, it has already been provided in the upper portion 3b of chamber 3, whereas if the gas 7 is other than air, the air already existing in the upper portion 3b of chamber 3 may be purged therefrom by displacing it with the desired gas 7.

(18) When it is desired to aspirate or dispense a quantity V of fluid 5, in step 103 a first pressure measurement P.sub.0 is taken by means of the pressure sensor 17, and if required, a temperature measurement T is taken by means of the temperature sensor 19.

(19) Subsequently, in step 104, the controller 21 causes pump 9 to operate so as to add (in the case of dispensing fluid) or remove (in the case of aspirating fluid) a known quantity of gas 7 from the upper portion 3b of chamber 3. In the dispensing example illustrated in FIG. 3, a quantity of gas 7 is added.

(20) There are several ways to determine this known quantity of gas 7. Firstly, the pump may be operated until a predetermined pressure P.sub.1 is measured in the chamber 3, the operation of the pump 9 being monitored so as to determine the volume of gas at the temperature and pressure upstream of the pump which has been pumped. This temperature and pressure can be determined e.g. by further temperature and pressure sensors. For instance, in the case of a reciprocating pump, the number of pump cycles may be counted, and a calibration curve used to determine the amount of gas, expressed in moles, pumped. In the case of a flowmeter being used, the controller 21 measures directly the volume pumped at the appropriate temperature and pressure, which can then be converted into moles via the well-known ideal gas equations, data tables or similar.

(21) Alternatively, a predetermined quantity of gas 7 can be pumped, and the pressure P.sub.1 measured after this pumping.

(22) In either case, the system can be assumed to be substantially isothermal if the speed of pumping is low in comparison to the thermal mass of the system and the rates of heat loss from the gas 7 in the chamber 3. In the opposite case, the pumping can be assumed to be isentropic. If required for the calculation methodology chosen, the continuous reduction in pressure may need to be taken into account when determining the quantity of gas 7 pumped as a function of the operation of the pump 9. For this purpose, pressure sensor 17 can take continuous measurements, which controller 21 can use to calculate the quantity of gas pumped. Other calculation methodologies may simply need only a before and after pressure measurement.

(23) Once pressure P.sub.1 has been reached, in step 105 the volume V.sub.1 (incidentally equal to V.sub.0 since this volume does not substantially change when pressure P is increased) of gas 7 in the chamber can be measured on the basis of P.sub.0, P.sub.1, the temperature, and the quantity of gas pumped.

(24) Most generically, V.sub.1 can be calculated based on the following equation:

(25) $V_1=\frac{\left(n_1-n_0\right)\mathrm{RT}}{\left(P_1-P_0\right)}$

(26) where (n.sub.1n.sub.0) is the number of moles of gas pumped by pump 9, R is the ideal gas constant, and T is the temperature.

(27) Taking a specific concrete example of a reciprocating pump 9 in which a number of strokes of the pump 9 can be counted, (n.sub.1n.sub.0) can be calculated as (n.sub.1n.sub.0))=f.sub.n(P.sub.1)s.sub.0, wherein f.sub.n(P.sub.1) is a predetermined calibration curve of the pump 9, i.e. the delivery rate as a function of counterpressure on the chamber 3 side of the pump 9, and s.sub.0 is the number of strokes of the pump 9 counted by the controller 21. An advantage of such a calibration curve based on counterpressure is that it is independent of whether the pump is increasing or decreasing the pressure in the chamber 3. Alternative equations based on the pressure of the gas supply can also be envisaged.

(28) The resulting equation is thus:

(29) $V_1=\frac{f_n\left(P_1\right)s_0\mathrm{RT}}{\left(P_1-P_0\right)}$

(30) The skilled person understands how to adapt this equation to other types of pump, including velocity pumps used in combination with a flow meter either upstream or downstream of the pump. For instance, for a lobe pump or a gear pump, the angle through which the pump drive turns, or the number of turns of the pump can be measured, and an appropriate calibration curve used.

(31) In step 106, on the basis of pressure P.sub.1 and the calculated volume V.sub.1 of gas in the chamber 3, a target pressure P2 can be calculated for aspirating or dispensing a desired volume V of fluid. To calculate P2 for a desired V to be dispensed or aspirated, the following equation can be used:

(32) $P_2=\frac{V_1^k}{{\left(V_1+V\right)}^k}{P}_1$

(33) where V.sub.1 is the gas volume within the containment before dispensing, V the dispensed liquid volume, k the polytropic exponent (the process may be isothermal or isentropic depending on system properties and gas expansion rate), P.sub.1 and P.sub.2 the pressure within the chamber 3 before and after dispensing or aspirating, respectively.

(34) In step 107, the controller 21 causes controllable valve 13 to open, and monitors the pressure P in the chamber 3 as it rises or falls. Once target pressure P2 is reached, the controller 21 closes valve 13 as final step 108. The desired volume V is thus aspirated or dispensed in function of signals from the pressure sensor 17.

(35) As can be seen from the above equations, it is not required to know a priori the volume of the chamber 3, or the quantity of fluid 5 therein, since these equations are entirely independent thereof. The apparatus 1 can thus be used with any desired chamber 3. Furthermore, no flowmeter or other equipment needs to be placed in the fluid path, removing the risk of contamination, failure of such a flowmeter, viscosity-related problems, or similar.

(36) FIG. 4 illustrates a particularly advantageous configuration of the apparatus 1 for use with a standard laboratory flask as chamber 3. In such a configuration, apparatus 1 is provided as a single unit provided with four ports, 23a, 23b, 23c and 23d. Port 23a leads from pump 9 is intended to be connected to a conduit passing through the cap of the flask and opening in upper portion 3b of chamber 3; port 23b leads to the controllable valve 13 and is intended to be connected to a conduit passing through the sealed cap of the flask and opening in lower portion 3a of chamber 3, below the intended level of fluid 5, and port 23c leads from controllable valve 13 is intended to be connected to nozzle 15. Port 23d leads to the pump 9 and is intended to be connected to a supply of air or another gas. Indeed, in the case in which the gas 7 is air, port 23d can be left open, or connected to a simple air filter to prevent ingress of dust. In the illustrated setup, the ports 23a-d are indeed connected with their intended components via appropriate conduits. Preferably, a hydrophobic membrane is arranged at port 23a to prevent liquid from reaching pump and pressure sensor of the apparatus when the flask serving as fluid chamber is turned upside down.

(37) Contrary to the arrangement illustrated in FIG. 1, pressure sensor 17 and temperature sensor 19 are integrated in apparatus 1 and are fluidically connected to the conduit extending between pump 9 and port 23a, so as to measure temperature and pressure in this conduit. As such, pressure sensor 17 and temperature sensor 19 are in fluid communication with the upper portion 3b of the chamber 3, via this conduit, port 3a, and the conduit opening in upper portion 3b of chamber 3. A further controllable valve may also be provided between pump 9 and port 23a, on either side of one or more of the sensors 17, 19. Furthermore, an optional check valve 25 may be provided adjacent to the pump 9 on one or the other sides thereof so as to prevent flow of gas 7 in an undesired direction.

(38) It should be noted that apparatus 1 may be divided into a control unit 1a comprising controller 21, pump 9, temperature sensor 19 and pressure sensor 17, and a dispensing/aspirating unit 1b comprising controllable valve 13.

(39) The arrangement of FIG. 4 can be used with a unidirectional pump 9 for either exclusively aspirating or exclusively dispensing fluid 5, or with a bidirectional pump 9 for both aspirating and dispensing. As such, it is suitable for use as a pipette system.

(40) FIG. 5 illustrates a partial view of a similar variant in which a unidirectional pump 9 can be used for both dispensing and aspiration. In this variant, a pair of three-way valves 27a, 27b are arranged so as to cause pump 9 to pump gas into or out of chamber 3. This arrangement can also be used in combination with any of the other variants illustrated above.

(41) Another adaptation illustrated in FIG. 5, which is independent of the three-way valve arrangement and can thus be applied in its absence, is that the pressure and temperature sensors 17, 19 have been moved into the dispensing unit, on the chamber-side of a controllable access valve 29 provided in fluid communication between the three-way valves 27a, 27b and the port 23a. Alternatively, the pressure and temperature sensors 17, 19 can be moved into the chamber 3. Such an arrangement permits construction of a manifold dispenser and/or aspirator. By duplicating the dispensing/aspirating unit 1b connected a single control unit 1a can control dispensing and aspiration from a plurality of individual chambers 3 by means of a plurality of dispensing/aspirating units 1b, each connected in fluid communication with a single control unit 1a via its corresponding access valve 29. In such an arrangement, the controller selects the chamber 3 being used by selectively opening the corresponding access valve 29 while leaving the others closed.

(42) Although the invention has been described with reference to specific embodiments, variations thereto are possible without departing from the scope of the invention as defined in the appended claims.