A SUCTION-DISPENSING APPARATUS AND ASSOCIATED METHODS.

Abstract

A controller configured to control one or more of the aspiration and dispensing of a primary fluid by an aspiration-dispensing apparatus, the aspiration-dispensing apparatus comprising a secondary fluid in working communication with the primary fluid, wherein the controller is configured to: receive measurement signaling for a monitored flow parameter of the secondary fluid; determine, using calibration data, a volume of primary fluid aspirated or dispensed based on the received measurement signaling, the calibration data defining a relationship between the volume of primary fluid aspirated or dispensed and the monitored flow parameter of the secondary fluid; and control the flow of primary or secondary fluid based on the determined volume to aspirate or dispense a specific volume of primary fluid.

Description

A SUCTION-DISPENSING APPARATUS AND ASSOCIATED METHODS Technical field This description relates to the aspiration and dispensing of fluids and to an apparatus and associated methods for its control. Background Existing suction-dispensing systems rely on time to monitor and control the volume of fluid aspirated or dispensed. However, because flow rate varies with pressure, the physical characteristics of the lines, and the viscosity of the fluid (among other factors), this approach is inaccurate and can result in wasted fluid. The apparatus and methods described herein may help to solve this problem. Compendium According to a first aspect, a controller is provided configured to control one or more of the aspiration and dispensing of a primary fluid by an aspiration-dispensing apparatus, the aspiration-dispensing apparatus comprising a secondary fluid in working communication with the primary fluid, wherein the controller is configured to: receive measurement signaling for a monitored flow parameter of the secondary fluid; To determine, using calibration data, a volume of primary fluid aspirated or dispensed based on the measurement signal received; the calibration data defines a relationship between the volume of primary fluid aspirated or dispensed and the monitored flow parameter of the secondary fluid; and to control the flow of primary or secondary fluid based on the determined volume to aspirate or dispense a specific volume of primary fluid. The aspiration-dispensing apparatus can be configured to aspirate or dispense primary fluid volumes in the milliliter range or less. orí? Lnn / zznz / E / YiAi The monitored flow parameter of the secondary fluid may comprise a displaced volume of secondary fluid, and the controller may be configured to: determine when the specific volume of primary fluid has been aspirated or dispensed based on the displaced volume of secondary fluid that reaches a first predefined threshold; and terminate the flow of primary or secondary fluid based on that determination. The controller can be configured to: to determine a sudden change in the monitored flow parameter of the secondary fluid, or a measurement of the monitored flow parameter that is above or below a second predefined threshold, based on the measurement signal received; and to terminate the flow of primary or secondary fluid based on such determination. The controller can be configured to generate a notification indicating a sudden change detected or a measurement above or below the second predefined threshold. The aspiration-dispensing apparatus may comprise a flow meter configured to measure the monitored flow parameter of the secondary fluid, a pressure regulator configured to regulate the pressure of the secondary fluid, and a valve configured to limit the flow of the primary or secondary fluid, and the controller may be configured to: Receive measurement signaling for the monitored flow parameter of the secondary fluid from the flow meter to allow determination of the volume of primary fluid drawn in or dispensed; and control the pressure regulator and valve based on the determined volume of primary fluid drawn in or dispensed to control the flow of primary or secondary fluid. The controller can be configured to generate calibration data that defines the relationship between the volume of primary fluid aspirated or dispensed and the monitored flow parameter of the secondary fluid. The controller can be configured to generate calibration data by: control the pressure regulator and valve to draw in or dispense one or more known volumes of primary fluid; orí? Lnn / zznz / E / YiAi receive, from the flow meter, respective measurements of the monitored flow parameter of the secondary fluid corresponding to one or more known volumes of primary fluid; and associate one or more known volumes of primary fluid with the respective measurements of the monitored flow parameter of the secondary fluid. The controller can be configured to associate the plurality of known volumes of primary fluid with the plurality of respective measurements of the monitored flow parameter of the secondary fluid by generating one or more of a lookup table, a graph, and an equation that defines the relationship between them. The controller can also be configured to control the primary or secondary fluid flow to dispense the specific volume of primary fluid to: control the pressure regulator and the valve to draw in a known volume of primary fluid; control the pressure regulator and valve to incrementally dispense the aspirated primary fluid during a recorded number of dispensing cycles; and determine a cycle volume based on the known volume of primary fluid and the recorded number of dispensing cycles. Each dosing cycle can have a known duration and the controller can also be configured to: determine a dispensing duration required to dispense the specific volume of primary fluid based on the cycle duration and cycle volume; and control the pressure regulator and valve to dispense the primary fluid for the determined dispensing duration. The controller can also be configured to: calculate a cycle volume for a plurality of different cycle durations; and associate the cycle volume with the duration of each cycle to generate more calibration data. The controller can be configured to associate cycle volume with the duration of each cycle by generating one or more of a lookup table, a graph, and an equation that defines the relationship between them. The controller can also be configured to: orí? Lnn / zznz / E / YiAi determine, using the additional calibration data, the cycle duration required to dispense the specific volume of primary fluid; and control the pressure regulator and valve to dispense the primary fluid for the determined cycle duration. According to another aspect, an aspiration-dispensing apparatus is provided comprising any controller described herein. The aspiration-dispensing apparatus may further comprise a flow meter circuit configured to convert an output signal from the flow meter into the received measurement signal, and a valve circuit configured to interconnect the valve with the controller. The suction-dispensing apparatus may comprise a plurality of primary fluid channels through which the primary fluid can flow into or out of the suction-dispensing apparatus, and a plurality of corresponding secondary fluid channels connected to the respective primary fluid channels to provide working communication between the primary and secondary fluids. Each primary or secondary fluid channel may comprise a filter configured to prevent the primary fluid from coming into contact with the flow meter. The plurality of primary fluid channels can be connected to a common primary manifold configured to receive and contain the primary fluid drawn through the plurality of primary fluid channels. Each primary fluid channel may comprise a tip configured to receive and contain the primary fluid drawn through the respective primary fluid channel. The tip can be a pipette tip for one or more aspiration (e.g., aspiration tip) and dispensing (e.g., dispensing tip). The tip can be configured for single use (i.e., disposable tip) or multiple use (i.e., reusable tip). Disposable tips can be used to reduce contamination between different primary fluid samples. The primary collector or tip may have a capacity sufficient to hold a volume of primary fluid required for multiple dispensing cycles. orí? Lnn / zznz / E / YiAi The plurality of secondary fluid channels can be connected to a common secondary manifold configured to interconnect the plurality of secondary fluid channels with the pressure regulator. The primary fluid can be a liquid and the secondary fluid can be a gas. According to another aspect, a method is provided for controlling one or more of the aspiration and dispensing of a primary fluid by an aspiration-dispensing apparatus, the aspiration-dispensing apparatus comprising a secondary fluid in working communication with the primary fluid, wherein the method comprises: receive measurement signaling for a monitored flow parameter of the secondary fluid; To determine, using calibration data, a volume of primary fluid aspirated or dispensed based on the measurement signal received; the calibration data defines a relationship between the volume of primary fluid aspirated or dispensed and the monitored flow parameter of the secondary fluid; and to control the flow of primary or secondary fluid based on the determined volume to aspirate or dispense a specific volume of primary fluid. According to another aspect, an aspiration-dispensing apparatus is provided as substantially described herein with reference to, and as illustrated by, the accompanying drawings. The steps of any method described herein do not have to be performed in the exact order described, unless explicitly indicated or understood by the person skilled in the art. The corresponding computer programs (which may or may not be recorded on a medium) to implement one or more of the methods described herein are also within the present description and covered by one or more of the illustrative modalities described. This description includes one or more corresponding aspects, illustrative modalities, or features, whether or not they are specifically indicated (or even claimed) in that combination or in isolation. The corresponding means for performing one or more of the functions discussed are also included in this description. The above summary is intended to be merely illustrative and not exhaustive. orí? Lnn / zznz / E / YiAi Brief description of the Figures A description is now provided, by way of example only, with reference to the accompanying schematic drawings, in which: Figure 1 schematically shows an aspiration-dispensing apparatus comprising a head assembly and a control assembly; Figure 2 graphically shows the calibration data for a dispensing operation of the aspiration-dispensing apparatus; Figure 3a shows a front view of the head assembly; Figure 3b shows the head assembly in cross-section; Figure 4 schematically shows a flow meter subassembly of the control assembly; Figure 5a shows a front view of a non-contact valve-tip subassembly; Figure 5b shows a front view of a valve-contact tip subassembly; Figure 5c shows an exploded view of the valve-contact tip subassembly; Figure 5d shows the cross-section of the valve-contact tip subassembly; Figure 6 shows in the form of a flowchart a method for controlling the aspiration-dispensing apparatus; and Figure 7 schematically shows a computer-readable means comprising a computer program configured to control, perform, or enable the method of Figure 6. Description of specific aspects / modalities As mentioned above, this description relates to an apparatus and associated methods for controlling the aspiration and / or dispensing of fluids. In particular, but not exclusively, the apparatus and associated methods can be configured to control the aspiration and / or dispensing of fluids in the milliliter volume range or below (e.g., microfluidics). This may be applicable to industries such as life sciences, healthcare, agri-food technology, and the environment. The modalities described below, represented in the figures, have been assigned reference numbers that correspond to similar characteristics of the modalities described above. For example, characteristic number 1 may also correspond to numbers 101, 201, 301, etc. These numbered characteristics may appear in the figures, but they may not have been directly mentioned in the description of these particular modalities. Nevertheless, they have been included in the figures to facilitate understanding of the additional modalities, especially in relation to the characteristics of the similar modalities described above. Figure 1 schematically shows an aspiration-dispensing apparatus comprising a head assembly 101 and a control assembly 102 which, in use, are in fluid communication 103 with each other through one or more fluid connectors 104. The head assembly 101 is configured to aspirate and / or dispense a primary fluid under the control of the control assembly 102. To enable this control, the aspiration-dispensing apparatus comprises a secondary fluid in working communication with the primary fluid. The term "working communication" in this context can be interpreted to mean that the secondary fluid is in direct or indirect contact (for example, through an intermediate component such as a piston) with the primary fluid such that a flow of the secondary fluid causes a corresponding flow of the primary fluid and vice versa. In some examples, the aspiration-dispensing apparatus may comprise a single primary fluid channel 105 through which the primary fluid can flow into or out of the aspiration-dispensing apparatus, and a single secondary fluid channel 406 connectable to the primary fluid channel 105 to provide working communication between the primary and secondary fluids. However, in other examples, the aspiration-dispensing apparatus may comprise a plurality of primary fluid channels 105 and a plurality of corresponding secondary fluid channels 406. The latter scenario may be useful when the aspiration-dispensing apparatus is used to aspirate from, or dispense to, a plurality of fluid origin containers, such as a multi-well plate or belt for processing multiple samples in parallel. The control assembly 102 itself comprises a pressure regulator 107, a flow meter subassembly 108, and a controller 109. The pressure regulator 107 is configured to regulate the pressure of the secondary fluid to induce its flow. In this example, the pressure regulator 107 is divided into two separate parts: a suction pressure regulator 107a that provides negative pressure (or vacuum) to the flow meter subassembly 108 for use in suctioning the primary fluid; and a dispensing pressure regulator 107b that provides positive pressure to the flow meter subassembly 108 for use in dispensing the primary fluid. In other examples, the suction pressure regulator 107a and dispensing pressure regulator 107b could be replaced by a single pressure regulator configured to provide both positive and negative pressure.As described in more detail below, the flow meter subassembly 108 comprises a flow meter 410 configured to monitor a secondary fluid flow parameter. Controller 109 is configured to control one or more of the primary fluid aspiration and dispensing by the head assembly 101. To accomplish this, controller 109 receives measurement signals for the monitored flow parameter of the secondary fluid from flow meter 410. Controller 109 then determines, using calibration data that defines a relationship between the volume of primary fluid aspirated or dispensed and the monitored flow parameter of the secondary fluid, a specific volume of primary fluid to aspirate or dispense using the received measurement signals (i.e., controller 109 monitors the aspirated / dispensed volume in substantially real time). Based on this determined / monitored volume, controller 109 controls the flow of primary or secondary fluid to aspirate or dispense a specific volume of primary fluid.The primary or secondary fluid flow can be controlled by adjusting pressure regulator 107 and / or a valve 511 configured to limit the primary or secondary fluid flow. The valve 511 can be located within the header assembly 101 (i.e., to limit the primary fluid flow) or the control assembly 102 (i.e., to limit the secondary fluid flow). orí? Lnn / zznz / E / YiAi Controller 109 may comprise a processor and a memory-stored computer program code. The memory and the computer program code are configured, in conjunction with the processor, to enable Controller 109 to perform the described functionality. The processor may be configured for the general operation of the suction-dispensing apparatus by providing signals to and receiving signals from the other components to manage their operation. The memory may be configured to store computer code configured to perform, control, or enable the operation of the suction-dispensing apparatus. The memory may also be configured to store configurations for the other components. The processor may access the memory to retrieve the configurations of the components in order to manage their operation.The processor may be a microprocessor, including an Application-Specific Integrated Circuit (ASIC). The memory may be a temporary storage medium such as volatile random-access memory (VRAM). Alternatively, the storage medium may be a permanent storage medium such as a hard disk drive, flash memory, or non-volatile random-access memory (NRAM). Additionally or alternatively, the controller 109 may comprise suitable logic circuitry configured to perform the described functionality. The monitored flow parameter of the secondary fluid can include a displaced volume of secondary fluid. In this scenario, controller 109 is configured to determine when a specific volume of primary fluid has been drawn in or dispensed based on the displaced volume of secondary fluid reaching a predefined threshold, and to terminate the flow of either primary or secondary fluid based on this determination. However, the monitored flow parameter is not limited to the displaced volume of secondary fluid. Other suitable examples include the pressure and flow rate of the secondary fluid (or a combination of two or more of these parameters). Unlike existing systems, the volume of primary fluid aspirated or dispensed is determined and controlled based on the monitored flow parameter of the secondary fluid, rather than relying solely on time. This makes the aspirated or dispensed volume less dependent on the variable characteristics of the apparatus or the primary fluid, resulting in greater accuracy and less waste. This approach also facilitates the automation of the aspiration or dispensing operation, thereby reducing human error and calibration time. In addition to determining and controlling the volume of primary fluid drawn or dispensed, monitoring a secondary fluid flow parameter also has other uses. For example, there may be a sudden change in the monitored flow parameter once all the primary fluid (excluding the dead volume for aspiration) has been drawn or dispensed. This is because there is usually a difference in the flow characteristics, and therefore displacement, of different fluids. This is particularly dramatic when there is a change of state from liquid to gas (or vice versa) and can be used to indicate the depletion of the primary fluid in the source container or the 101 head assembly.In this scenario, controller 109 can be configured to terminate the primary or secondary fluid flow based on a sudden change in the monitored secondary fluid flow parameter, thus interrupting the aspiration or dispensing operation. Controller 109 can also be configured to generate a notification indicating the detected sudden change, for the benefit of the aspiration-dispensing unit user. A detectable change in the monitored flow parameter may also occur due to wear or failure of a component in the suction-dispensing unit. This could happen, for example, due to a pressure change caused by a leak in the system. In this case, the 109 controller can be configured to terminate the primary or secondary fluid flow if a flow parameter measurement falls above or below a second, predefined threshold. This allows for inspection and repair or replacement of the relevant component. Similar to a sudden change detected in the monitored flow parameter, the 109 controller can also be configured to generate a notification indicating that the monitored flow parameter is above or below the second, predefined threshold. This alerts the user to the potential need for maintenance of the suction-dispensing unit. While the primary fluid would typically be a liquid and the secondary fluid a gas, the aspiration-dispensing apparatus is not limited in this way. For example, both the primary and secondary fluids could be liquids as long as the secondary fluid does not mix with the primary fluid or cause a chemical or biological change in it. In this respect, the primary fluid could be water and the secondary fluid could be a hydrophobic liquid such as an oil (or vice versa). Furthermore, when the primary fluid is a liquid and the secondary fluid is a gas, the gas must be sufficiently inert and insoluble in the primary fluid so that it does not cause a chemical or biological change in the primary fluid, or a pressure change that could potentially affect calibration.Ideally, the primary and secondary fluids would also exhibit sufficiently distinct flow parameters to allow for the detection of primary fluid depletion during a dispensing operation based on a sudden change in flow parameter. Examples of primary fluids include biological or nucleic acid samples (such as human, plant, or animal biological materials or genetic samples), chemicals, and reagents (such as nucleic acid sample preparation reagents, molecular biology reagents, and polymerase chain reaction reagents). For example, the aspiration-dispensing apparatus can be used to aspirate and / or dispense saliva samples being tested for diseases such as COVID-19.Saliva samples collected in the field can vary in viscosity and consistency, but this apparatus is well-suited to such primary fluids because it does not rely on time to monitor and control the aspirated or dispensed volume. The aspiration-dispensing apparatus can also be used with primary fluids such as oligo synthesis reagents, genome sequencing samples, and reagents for oligonucleotide production. Examples of secondary fluids include air, helium, nitrogen, and argon. As mentioned previously, controller 109 uses calibration data to determine / control the volume of primary fluid drawn in or dispensed. The calibration data defines the relationship between the volume of primary fluid drawn in or dispensed and the flow parameter of the secondary fluid. This data can be generated by controller 109 for each type of primary fluid. To generate the calibration data, controller 109 can be configured to control pressure regulator 107 and / or valve 511 to draw in or dispense one or more known volumes of primary fluid and receive (from flow meter 410) respective measurements of the flow parameter of the secondary fluid corresponding to one or more known volumes of primary fluid.Controller 109 can then associate one or more known volumes of primary fluid with the respective measurements of the secondary fluid flow parameter for use in subsequent aspiration or dispensing operations, for example, by generating one or more of a lookup table, a graph, and an equation that defines the relationship between them. In practice, however, the aspiration and dispensing operations can be calibrated separately. This is because the aspiration of the primary fluid used by the aspiration and dispensing apparatus is independent of the fluid's viscosity, while the dispensing of the primary fluid may not be. Regarding aspiration, controller 109 can initiate the calibration process by controlling pressure regulator 107 and valve 511 to draw primary fluid from a source container holding an unknown volume of primary fluid until a sudden change in the monitored flow parameter of the secondary fluid is detected. This sudden change in the monitored flow parameter indicates that the head assembly 101 has drawn as much primary fluid as possible and is now drawing air (or another ambient gas). Any primary fluid remaining in the source container is referred to as the aspiration dead volume.This is the volume of primary fluid that the printhead assembly 101 cannot draw from the source container due to physical constraints such as the size and shape of the source container relative to the printhead assembly 101's tip(s) 512 (the latter are described in more detail below). The drawn primary fluid is then dispensed as waste. A known calibration volume Vi of primary fluid is then added to the source container (which still contains the primary fluid suction dead volume) before controller 109 draws the primary fluid until a sudden change in the monitored flow parameter is detected, as before. If the monitored flow parameter is the displaced volume of secondary fluid V2, a suction calibration gain value G can be determined using a measurement of the displaced volume V2 of the secondary fluid along with knowledge of any pre-existing gain value Go, according to the following equation: / V2\ G = G0x viq / The displaced volume of secondary fluid V2 measured during any subsequent aspiration operation can then be multiplied by the original aspiration calibration gain value Lnn / zznz / E / YiAi to provide a more accurate measurement of the aspirated volume of primary fluid. The viscosity of the fluid affects the flow rate of the primary fluid exiting the nozzle(s) 512 of the head assembly and, therefore, the length of time valve 511 needs to remain open to dispense a particular volume of primary fluid. As such, controller 109 can be configured to generate additional calibration data for dispensing operations. In this regard, controller 109 can first control pressure regulator 107 and valve 511 to draw a known volume of primary fluid. This can be achieved by using the calibration data generated for the draw operations to terminate the draw operation once the known volume has been drawn, or by drawing all the primary fluid in the source container minus the draw dead volume, as before. Once the known volume has been aspirated, controller 109 gradually dispenses the aspirated primary fluid over a recorded number of dispensing cycles until a sudden change in the monitored flow parameter of the secondary fluid is detected. This sudden change in the monitored flow parameter indicates that the head assembly 101 has dispensed the maximum possible amount of primary fluid and is now aspirating air (or another secondary fluid). Any primary fluid remaining in the head assembly 101 is called the dispensing dead volume. This is the volume of primary fluid that the head assembly 101 cannot aspirate from the system. In practice, controller 109 can gradually dispense the aspirated primary fluid by periodically opening valve 511 for a known time (or valve opening time).Controller 109 then determines a cycle volume (i.e., the dispensed volume of primary fluid per dispensing cycle) by dividing the known volume of primary fluid by the recorded number of dispensing cycles. This data can then be used during future dispensing operations to dispense a specific volume of primary fluid using multiple dispensing cycles. In this scenario, controller 109 determines the dispensing duration required to dispense the specific volume of primary fluid by dividing the specific volume by the cycle volume and multiplying by the cycle duration. It then controls pressure regulator 107 and / or valve 511 to dispense the primary fluid for the determined dispensing duration.The 109 controller can also be configured to calculate a cycle volume for a plurality of different cycle durations and associate the cycle volume with the cycle duration in the form of a lookup table, graph and / or equation that defines the relationship between them. Figure 2 shows an example of the additional calibration data for an experimental dispensing operation of the aspiration-dispensing apparatus. During this experiment, water and air were used as the primary and secondary fluids, respectively, and the head assembly 101 had eight primary fluid channels 105, each comprising a tip 512 through which the primary fluid was drawn in and dispensed. For each tip 512, the cycle volume was determined for five different cycle durations and then plotted. As can be seen from the data, there were slight variations in cycle duration (valve opening time) among the tips 512, but an approximately linear relationship for each tip 512. This data can then be used during future dispensing operations to dispense a specific volume of primary fluid using a single dispensing cycle.In this scenario, controller 109 determines the cycle duration required to dispense the specific volume of primary fluid by reading, interpolating, or extrapolating additional calibration data. It then controls pressure regulator 107 and / or valve 511 to dispense the primary fluid for the determined cycle duration. As shown in Figure 1, the head assembly 101 comprises several additional components, which will now be described. In this example, the head assembly 101 comprises a plurality of primary fluid channels 105 (8 instead of a single primary fluid channel 105), each of which has a valve-tip subassembly 113 through which the primary fluid can flow into or out of the aspiration-dispensing apparatus. The valve-tip subassembly 113 itself comprises a tip 512 and a valve 511 configured to restrict the flow of the primary fluid through it. The plurality of primary fluid channels 105 are connected to a common primary manifold 114 configured to receive and contain the primary fluid drawn through the respective valve-tip subassemblies 113.In this respect, the primary collector 114 may have a capacity that is sufficient to contain a volume of primary fluid required for multiple dispensing cycles from each primary fluid channel 105. The header assembly 101 further comprises a valve cover 115 configured to protect the valve-tip subassemblies 113 from damage, a removable manifold cover 116 configured to facilitate cleaning of the common primary manifold 114 below, and a manifold assembly 117 configured to mechanically fasten the header assembly 101 to another object. The latter feature can help ensure that the primary fluid channels 105 are in a fixed orientation (e.g., substantially vertical in use) between consecutive aspiration or dispensing operations for greater consistency. The header assembly 101 also comprises a valve circuit configured to interconnect the valve 511 of each valve-tip subassembly 113 with the controller 109 of the control assembly 102.In this example, the valve circuit comprises a circuit board 118 and a wired connection 119 between the circuit board 118 and the controller 109, but a wireless connection could be used instead. The circuit board 118 may comprise indicator lights (or light-emitting diodes) that indicate the open or closed state of each valve 511. Figures 3a and 3b show front and cross views of head assembly 101. The cross section in Figure 3b was taken through line AA as indicated in Figure 3a. The various components are as described above in relation to Figure 1 and are therefore indicated by their corresponding part numbers. Figure 4 schematically shows the flow meter subassembly 108 of the control assembly 102. In this example, the flow meter subassembly 108 comprises a plurality of secondary fluid channels 406 (8 instead of a single secondary fluid channel 406) that can be connected to the corresponding primary fluid channels 105 of the head assembly 101 through a plurality of respective fluid connectors 104. The plurality of secondary fluid channels 406 is also connected to a common secondary manifold 420 of the flow meter subassembly 108, which is configured to interconnect the plurality of secondary fluid channels 406 with the pressure regulator 107 through a pressure inlet 421. orí? Lnn / zznz / E / YiAi The flow meter subassembly 108 further comprises a respective flow meter 410 configured to independently monitor the flow parameter of the secondary fluid within each of the different secondary fluid channels 406, and a flow meter circuit 422 configured to convert the output signal of each flow meter 410 into measurement signaling suitable for use by the controller 109. In addition, each of the secondary fluid channels 406 comprises a filter 423 configured to prevent the primary fluid from coming into contact with and potentially damaging the flow meter 410 (although fluid connectors 104 could instead be placed within the primary fluid channels 105 or between the primary fluid channel 105 and secondary fluid channel 406).Although flow of primary fluid into the secondary fluid channels 406 is unlikely with the monitored secondary fluid flow parameter used to control primary fluid aspiration and dispensing, the filters 423 serve as a safety feature should it occur. The specific filters required will depend on the type of primary fluid. For example, hydrophobic filters can be used when the primary fluid is water, and oleophobic filters can be used when the primary fluid is oil. Figure 5a shows a non-contact valve-tip subassembly 113 of the head assembly 101. As mentioned previously, the primary fluid enters and exits the head assembly 101 through the valve-tip subassembly 113. In this example, the valve-tip subassembly 113 comprises a tip 512, a valve 511, and a mandrel 524. The tip 512 provides a metered orifice that regulates the primary fluid velocity under pressure according to Bernoulli's principle, but it does not make contact with the fluid container into which the primary fluid is dispensed during the dispensing operation (hence, non-contact). The valve 511 limits the flow of the primary fluid through it according to the instructions of the controller 109 (typically between open and closed states), while the mandrel 524 allows access to the tip 512 and the valve 511 for maintenance or replacement. Figures 5b-d show front, exploded, and cross-sectional views of a contact valve-tip subassembly 525, respectively. The cross-section in Figure 5d was taken through line BB as shown in Figure 5b. The contact valve-tip subassembly 525 comprises a tip 528, a butt seal 526, a valve 511, a mandrel 524, and a valve-tip fitting. 527. The mandrel 524 is similar to that in Figure 5a. The valve-to-tip fitting 527 is used to connect the valve 511 to the tip 528, and the O-ring 526 seals the valve-to-tip fitting 527 to provide a fluid-tight connection. Unlike the valve-tip subassembly 113 in Figure 5a, this tip 528 is configured to break the surface of the primary fluid in the fluid bowl during the dispensing operation (hence, contact). In addition, the tip 528 is configured to receive and contain the aspirated primary fluid and, in some cases, may have sufficient capacity to hold a volume of primary fluid required for multiple dispensing cycles. As such, the tip 528 of Figures 5b–d eliminates the need for a common primary manifold 114 and manifold cover 116 in the head assembly 101.To account for this change, each 304 fluid connector can be connected directly to the 511 valve of a valve-contact tip subassembly instead of the 316 manifold cover per the 301 header assembly in Figure 3b. A more detailed description of the aspiration and dispensing modes of the aspiration-dispensing apparatus in Figure 1 is provided below. In aspiration mode, the controller 109 sends a start signal to the aspiration pressure regulator 107a and the valve circuit to open valve 511 of the valve-tip subassembly 113 and apply negative pressure to the pressure inlet 421 of the common secondary manifold 420. This causes secondary fluid to flow from the primary fluid channels 105 through the fluid connectors 104 into the secondary fluid channels 406. The secondary fluid flow causes the primary fluid to be drawn through the tips 512 and into the common primary manifold 114.During this process, the flow of secondary fluid through the secondary fluid channels 406 is monitored by the respective flow meters 410, whose output signals are converted by the flow meter circuit 422 into measurement signals suitable for the controller 109. The controller 109 monitors the volume of primary fluid drawn in based on the measurement signals and calibration data, and terminates the flow of secondary fluid once the desired volume of primary fluid has been drawn in. Termination of the secondary fluid flow is accomplished by sending a termination signal to the suction pressure generator 107a and the valve circuit to close valve 511 of the valve-tip subassembly 113 and eliminate the negative pressure applied to the pressure inlet 421 of the common secondary manifold 420. orí? Lnn / zznz / E / YiAi In dispensing mode, controller 109 sends a start signal to the dispensing pressure regulator 107b and the valve circuit to open valve 511 of the valve-tip subassembly 113 and apply positive pressure to the pressure inlet 421 of the common secondary manifold 420. This causes secondary fluid to flow from the secondary fluid channels 406 through the fluid connectors 104 into the primary fluid channels 105. The flow of secondary fluid causes primary fluid to be dispensed from the common primary manifold 114 and through the tips 512. The primary fluid can be dispensed in a single (longer) dispensing cycle or incrementally over a plurality of (shorter) dispensing cycles.During this process, the flow of secondary fluid through the secondary fluid channels 406 is monitored by the respective flow meters 410, whose output signals are converted by the flow meter circuit 422 into measurement signals suitable for the controller 109. The controller 109 monitors the volume of primary fluid dispensed based on the measurement signals and calibration data, and terminates the flow of secondary fluid once the desired volume of primary fluid has been dispensed. Termination of the secondary fluid flow is accomplished by sending a termination signal to the dispensing pressure generator 107b and the valve circuit to close valve 511 of the valve-tip subassembly 113 and eliminate the positive pressure applied to the pressure inlet 421 of the common secondary manifold 420. Figure 6 shows the main steps 629-632 of a method for controlling one or more of the aspiration and dispensing of a primary fluid by means of an aspiration-dispensing apparatus described herein. As illustrated, the method generally comprises: receiving 629 measurement signaling for a monitored flow parameter of the secondary fluid; determining 630, using calibration data, a volume of primary fluid to be aspirated or dispensed based on the received measurement signaling, the calibration data defining a relationship between the volume of primary fluid aspirated or dispensed and the monitored flow parameter of the secondary fluid; controlling 631 the flow of primary or secondary fluid based on the determined volume; and aspirating or dispensing 632 a specific volume of primary fluid. Figure 7 schematically illustrates a computer-readable / processor medium 733 that provides a computer program. The computer program may comprise computer code configured to perform, control, or enable one or more of the steps of Method 629-632 in Figure 6. In this example, the computer-readable / processor medium 733 is a disk such as a digital versatile disc (DVD) or a compact disc (CD). In other embodiments, the computer-readable / processor medium 733 may be any medium 733 that has been programmed to perform an inventive function. The computer-readable / processor medium may be a removable memory device such as a memory stick or a memory card (SD, mini SD, micro SD, or nano SD). The applicant hereby describes, individually, each feature described herein and any combination of two or more such features, to the extent that such features or combinations can be implemented based on the present specification as a whole, in light of the common general knowledge of a person skilled in the art, regardless of whether such features or combinations of features solve any problem described herein, and without limitation to the scope of the claims. The applicant indicates that the aspects / modalities described may consist of any individual feature or combination of features. In view of the foregoing description, it will be evident to a person skilled in the art that various modifications may be made within the scope of the description.

Claims

1. A controller configured to control one or more of the aspiration and dispensing of a primary fluid by an aspiration-dispensing apparatus, the aspiration-dispensing apparatus comprising a secondary fluid in working communication with the primary fluid, wherein the controller is configured to: receive measurement signaling for a monitored flow parameter of the secondary fluid; determine, using calibration data, a volume of primary fluid aspirated or dispensed based on the received measurement signaling, the calibration data defining a relationship between the volume of primary fluid aspirated or dispensed and the monitored flow parameter of the secondary fluid; and control the flow of primary or secondary fluid based on the determined volume to aspirate or dispense a specific volume of primary fluid.

2. The controller of claim 1, wherein the aspiration-dispensing apparatus is configured to aspirate or dispense primary fluid volumes in the volume range of milliliters or less.

3. The controller of claim 1 or 2, wherein the monitored flow parameter of the secondary fluid comprises a displaced volume of secondary fluid, and wherein the controller is configured to: determine when the specified volume of primary fluid has been drawn in or dispensed based on the displaced volume of secondary fluid reaching a first predefined threshold; and terminate the flow of primary or secondary fluid based on such determination.

4. The controller of any preceding claim, wherein the controller is configured to: determine a sudden change in the monitored flow parameter of the secondary fluid, or a measurement of the monitored flow parameter that is above or below a second predefined threshold, based on received measurement signaling; and terminate the flow of the primary or secondary fluid based on such determination.

5. The controller of claim 4, wherein the controller is configured to generate a notification indicative of the detected sudden change or measurement above or below the second predefined threshold.

6. The controller of any preceding claim, wherein the aspiration-dispensing apparatus comprises a flow meter configured to measure the monitored flow parameter of the secondary fluid, a pressure regulator configured to regulate the pressure of the secondary fluid, and a valve configured to limit the flow of the primary or secondary fluid, and wherein the controller is configured to: receive measurement signaling for the monitored flow parameter of the secondary fluid from the flow meter to allow determination of the volume of primary fluid aspirated or dispensed; and control the pressure regulator and the valve based on the determined volume of primary fluid aspirated or dispensed to control the flow of primary or secondary fluid.

7. The controller of any preceding claim, wherein the controller is configured to generate calibration data that defines the relationship between the volume of primary fluid drawn in or dispensed and the monitored flow parameter of the secondary fluid.

8. The controller of claim 7 when dependent on claim 6, wherein the controller is configured to generate the calibration data by: controlling the pressure regulator and valve to draw in or dispense one or more known volumes of primary fluid; receiving, from the flow meter, respective measurements of the monitored flow parameter of the secondary fluid corresponding to one or more known volumes of primary fluid; and associating the one or more known volumes of primary fluid with the respective measurements of the monitored flow parameter of the secondary fluid.

9. The controller of claim 8, wherein the controller is configured to associate the plurality of known volumes of primary fluid with the plurality of respective measurements of the monitored flow parameter of the secondary fluid by generating one or more of a lookup table, a graph, and an equation defining the relationship between them.

10. The controller of any of claims 7 to 9 when dependent on claim 6, wherein the controller is further configured to control the flow of primary or secondary fluid to dispense the specified volume of primary fluid by: controlling the pressure regulator and valve to draw in a known volume of primary fluid; controlling the pressure regulator and valve to incrementally dispense the drawn-in primary fluid during a recorded number of dispensing cycles; and determining a cycle volume based on the known volume of primary fluid and the recorded number of dispensing cycles.

11. The controller of claim 10, wherein each dispensing cycle has a known duration and wherein the controller is further configured to: determine a dispensing duration required to dispense the specified volume of primary fluid based on the cycle duration and cycle volume; and control the pressure regulator and valve to dispense the primary fluid for the determined dispensing duration.

12. The controller of claim 10, wherein the controller is further configured to: repeat the steps of claim 10 for a plurality of different cycle durations; and associate the cycle volume with the duration of each cycle to generate more calibration data.

13. The controller of claim 12, wherein the controller is configured to associate the cycle volume with the duration of each cycle by generating one or more of a lookup table, a graph, and an equation that defines the relationship between them.

14. The controller of claim 12 or 13, wherein the controller is further configured to: determine, using the additional calibration data, the cycle duration required to dispense the specified volume of primary fluid; and control the pressure regulator and valve to dispense the primary fluid for the determined cycle duration.

15. An aspiration-dispensing apparatus comprising the controller of any preceding claim.

16. The aspiration-dispensing apparatus of claim 15 when dependent on claim 6, wherein the aspiration-dispensing apparatus further comprises a flow meter circuit configured to convert an output signal from the flow meter into the received measurement signal, and a valve circuit configured to interconnect the valve with the controller.

17. The suction-dispensing apparatus of claim 15 or 16, wherein the suction-dispensing apparatus comprises a plurality of primary fluid channels through which the primary fluid can flow into or out of the suction-dispensing apparatus, and a plurality of corresponding secondary fluid channels connected to the respective primary fluid channels to provide working communication between the primary and secondary fluids.

18. The aspiration-dispensing apparatus of claim 17 when dependent on claim 16, wherein each primary or secondary fluid channel comprises a filter configured to prevent the primary fluid from coming into contact with the flow meter.

19. The aspiration-dispensing apparatus of claim 17 or 18, wherein the plurality of primary fluid channels is connected to a common primary manifold configured to receive and contain the primary fluid aspirated through the plurality of primary fluid channels.

20. The aspiration-dispensing apparatus of claim 17 or 18, wherein each primary fluid channel comprises a tip configured to receive and contain the primary fluid aspirated through the respective primary fluid channel.

21. The aspiration-dispensing apparatus of claim 19 or 20, wherein the primary collector or tip has a capacity sufficient to hold a volume of primary fluid required for multiple dispensing cycles.

22. The aspiration-dispensing apparatus of any of claims 17 to 21 when dependent on claim 16, wherein the plurality of secondary fluid origin channels is connected to a common secondary manifold configured to interconnect the plurality of secondary fluid channels with the pressure regulator.

23. The aspiration-dispensing apparatus of any of claims 15 to 22, wherein the primary fluid is a liquid and the secondary fluid is a gas. 24.A method for controlling one or more of the aspiration and dispensing of a primary fluid by an aspiration-dispensing apparatus, the aspiration-dispensing apparatus comprising a secondary fluid in working communication with the primary fluid, wherein the method comprises: receiving measurement signaling for a monitored flow parameter of the secondary fluid; determining, using calibration data, a volume of primary fluid aspirated or dispensed based on the received measurement signaling, the calibration data defining a relationship between the volume of primary fluid aspirated or dispensed and the monitored flow parameter of the secondary fluid; and controlling the flow of primary or secondary fluid based on the determined volume to aspirate or dispense a specific volume of primary fluid.

25. A computer program comprising computer code configured to perform the method of claim 24.

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