HYBRID PIPETE SYSTEM WITH DISPOSABLE TIP INSERTIONFIELD OF THE INVENTIONThis invention relates to pipetting systems and methods, including manual and automatic systems, which today consist of a device or equipment for pipetting and a container with disposable tips inside, which are usually treated separately. In a particular sense, systems, equipment and methods that perform aspiration and dispensing operations are considered, as is the case with piston pipettes, which are used to transfer liquids from one container to another (s).
OBJECT OF THE INVENTIONCurrently, it is common to use pipettes for the transfer of liquids in research or clinical laboratories, and in industries such as pharmaceutical, genomics, food, diagnostics, among others. In this invention a hybrid pipetting system is established, which can have components of different nature (mechanical, electronic, etc.), and is more complete but also more complex than the known ones. It is shown that it contains new features and more functions, through subsystems defined on what today would be the conjunction of the pipetting device or equipment and the container or tray with disposable tips. This also gives rise to a method for the replacement of disposable tips, and in particular a subsystem insertion / expulsion of disposable tips is introduced, based on two possible architectures: 1) with movement ofthe mouthpiece, or 2) with movement of the disposable tip. Systems, methods and / or devices for the replacement of disposable tips are not included as part of the manual pipettes that are on the market, be they mechanical, electronic or hybrid. The system and the method obtained do not have any restrictions regarding the way of use and its possible applications, although examples of derived devices are given, without being thereby limited in any way to them. It is oriented, in a particular sense, towards manual pipettes where the way in which the replacement of disposable tips is performed is an ergonomic property. Another aspect considered within the pipetting system is the introduction of a container with a double box, which allows a quick and easy recycling of the plastic. With the same characteristics and properties presented, the pipetting system can be applied to the case of automated equipment that uses a robotic arm for the pipetting process. The application (manual or automatic) of the system and the method developed in this invention includes improving the relationship of insertion / ejection forces as well as an optimization in the performance of the device.
INTRODUCTION AND BACKGROUNDPipetting systems have diverse applications in science and technology, as well as in related industries, such as food, biotechnology, molecular biology, genetics, health, biomedicine, environment, chemistry and pharmacology, without being limited to them. In particular, the transfer and dispensing ofLiquids are carried out in analysis and research laboratories, hospitals and in all those places that require liquid handling in a precise manner.
For a better understanding of the present development, we first consider the systems at a general level and include some useful definitions below.1 - . 1 - System: Set of components or organized elements that are in interaction with each other, seeking common goals, in a time reference to produce an output (such as information, material and / or energy). It can be represented at different levels and here we consider it, from a basic point of view, through an abstract representation. Although also, from a physical or more realistic point of view can be represented through modules, components and their connections. When these are of a different type or nature, the system is said to be hybrid, and it can also be divided into parts for a better understanding or grouping of such components.2- Block diagram: Represents the structure of a system with an emphasis on the function of the blocks. It then shows the parts that form it and the way in which they relate to each other, but it does not represent the physical aspect or its functioning. Each part can actually be a set of parts that are grouped together when they fulfill a function. In general, it is used as a description (that we call) at level 1, which is less detailed in terms of implementation and more oriented to the understanding of important concepts. A block is considered a coherent set of things(components or modules in our case) with some common characteristics, or that develop a function or operation as a whole.3- Schematic diagram: Here they replace all or some of the blocks in the block diagram of a system and break it down into modules, components and their connections that may or may not be abstract, using in part a graphic language as well as more realistic representations . This means that this type of diagram is closer to a real representation (in relation to the block diagram) and is an example (we call at level 2) quasi real of a device or equipment. But the fundamental property that it contains is that it clearly defines the architecture of the system at a more specific level than the case of the block diagram, allowing to visualize the subsystems that integrate it.4- Device diagram: It shows the system in a more detailed level to what the schematic representation is, since the type, nature or classification of the same is specified, and we say then that it is a description at level 3. A device is defined as an artifice arranged for the execution of one or more actions or functions, considering here that it can be manual, automatic or hybrid (semiautomatic). Physically it is composed of components, which can be grouped into modules, and from a practical point of view it can be considered as a concrete example of a system. In what concerns us here, manual pipettes and pipetting heads for automated equipment are examples of pipetting devices.5- Subsystem: Subset of elements of a system, according to the criterion that is classified or that is requested to make the separation. As elements, we refer toto blocks, components or modules, that is to say that a subsystem can be defined in the three different levels, however it is from level 2 when it is clearly separated from the blocks that are introduced in level 1. In level 3, already specifying the subsystem based on the components, is defined by these and can then include components that are replacing different blocks, although this is also up to who makes the design. Two or more subsystems can be superimposed, so they share some elements. However, it is necessary to establish a criterion that allows to differentiate two subsystems, so that the set is not redundant. We use this later with direct application to the pipetting system that is the object of this invention.6- Flow diagram: It is a graphic representation of an algorithm or process, and they use symbols with well-defined meanings that represent the steps of the algorithm, where the direction of execution is represented by arrows that connect the starting points with the intermediate steps and the end of the process.7- Component: each of the basic constituents that are involved in the structure and operation of a device or equipment. In the section referring to the detailed description we consider components that are (without being limited) of electronic, mechanical, pneumatic, optical, magnetic, electromagnetic, acoustic and / or hybrid type between at least two of the above. The components interact or link to each other through connections.8- Module: unit set of grouped components, which are used in the implementation of a system, to make it easier, regular and economic. Thisconstituted by components, provided that a certain grouping criterion can be used on it, developing the whole a defined function or operation or part of them. However, a module is defined by the function it performs within the system and not by its internal components. Different modules are coupled or linked through connections, the same or of the same nature as the components.9- Connection: It is the functional link that is established between two elements of the same characteristics or hierarchical levels that are representing something or system, ie between pairs of blocks, modules or components, which allows them to establish an interaction between one and other. They are represented by lines or arrows (in this case giving a sense of flow).10- Coupling: is the adjustment that is achieved between two components or structures to form a larger set and so that they can be united when they develop a set function.
We see then of the previous thing that the representation of a system we give it basically in three level, although there can be sublevels where some parts or components are specified in a more detailed way. At level 1 we have the block diagram, which establishes the functions and which are the possible subsystems. At level 2 the schematic diagram already allows to establish some modules or components at a general level, allowing to define the subsystems, which could even contain several of the functions indicated by the block diagrams of level 1. At level 3 it is already a diagram of device, which allows defining it from the point of view of type, nature, form and components,although as in the previous level there may be several sublevels with more details between one and the other.
Referring to pipetting systems and everything related to the process, devices and mechanisms included in them, it is important to also consider some concepts that place us in context. We also include the patent literature that can be found in relation to the concepts, selecting very few but relevant and the most recent examples. This allows establishing the scope of what is today in relation to such issues, and to explain in the following sections what are the novelties of the present invention.
Pipetting system.
The pipetting operation is one in which a precise and relatively small amount of liquid is taken, which is then introduced (dispensed) into a second container for analysis or some other type of testing or function, as in the case of dilution and / or mixture of liquids, but without being limited. In the present context, the operation is also mentioned as aspirated / dispensed due to the characteristics of the system responsible for carrying it out, and which uses a pressure chamber with a piston or plunger, as well as disposable tips where the aspirated liquid is introduced which is then dispensed.
In order to have a unified criterion, here we consider that a pipetting system is one that is composed of a pipetting device and equipment.a container or tray with disposable tips inside. The pipetting systems have NxM nozzles to perform the operation, where N = 1, 2, ..., M = 1, 2, ..., each using its corresponding disposable tip.
Table 1 - Patents that refer to and treat pipetting systemsIf the patent literature is analyzed, it can be verified that there is no clear definition of what a pipetting system is, although in US Patent 3,494,201 (Roach, 1968) it is where the same sense as we use here is given. In the references in Table 1 we can find modifications to the filling (with a liquid) of disposable tips by devices different from those commonly used (pistons), changes in the operating mechanism to allow the aspiration of several samples separated by an air layer , fiexibilization of the taking of disposable tips in automated equipment, or introduction of sensors and control loops to improve the accuracy of the aspirate, alsoinvolves the use of computer systems for the calibration of aspirated volume of samples.
We take the pipetting devices as simpler system examples than the case of a computer, which can be made up of several devices, and develops more complex tasks. Without being limited to the concept, we can associate in principle what is a device with a pipette or manual micropipette, which in turn can be mechanical, electronic or hybrid, but we also associate it with the head of an automated pipetting equipment, which has an NxM number of nozzles (in matrix form). This system (head + container) is operated by a robotic arm, such as a coordinate table or a SCARA, although there are also examples in which it can be operated manually.
Disposable tip (pipette tip, in English).
A different disposable tip is used in each liquid aspiration / dispensing operation, ie for each sample that is taken with the pipetting device or equipment, and it is important to avoid contamination by carry between different samples. Since it is made of plastic material, it is important to be able to recycle this material then. A typical disposable tip is hollow in its interior and has circular symmetry (like a conical tube), and is formed by a crown with internal channel, which can be conical or cylindrical with some longitudinal projections, and a body or frustoconical prolongation. The crown of the disposable tip has a larger external diameterthat the conical body, which has a small hole at its distal end. The nozzle of the device or pipetting equipment is inserted inside the crown of the disposable tip, and is maintained there by friction, exerting a certain force that can reach 5 kg. This value is not exact and has been greatly reduced by the use of more suitable materials or systems.
Table 2 - Patents related to disposable tips and coupling between these with the nozzle.
In the examples in Table 2, ways of achieving a good seal between the pipette nozzle and the disposable tip are developed to ensure accuracy, while reducing the force required to insert and eject the disposable tips. Different ways to achieve sealing are shown, such as: a disposable tip whose crown has a protrusion to facilitateinsertion and expulsion. Different arrangements and designs of channels in the crown are also claimed to decrease the forces of insertion / expulsion, which is achieved using a material similar to rubber to be flexible and facilitate sealing. It involves the use of a flexible hinge that facilitates the insertion, ejection and sealing, as well as an o-ring (or packaging) on the pipette nozzle, or disposable tips joined by a strip for use with multipipettes. In the case of automated equipment, two cylindrical portions of different diameters can be used, both with protruding rings, with which the disposable tip makes contact and seals, while the disposable tip has a collar in which two zones are located ( steps) of different diameters that make contact with the rings of the nozzle. The integration of an electrode in the passage of the flow is used to detect, among other things, the amount of liquid, the aspirate, the presence of bubbles and the speed of aspiration. Also included is a disposable tip made of a water repellent polymer substrate and which prevents biological samples from adhering to the outside of the tip during dispensing.
Container or tray (rack, in English) with disposable tips.
Typically the disposable tips are supplied in containers or trays that have holes to house a total of NxM disposable tips (with N = 1, 2, ..., M = 1, 2, ...). Many patents can be found regarding disposable tip containers where it is generally considered separate from the pipetting device or equipment. Disposable tips are inside theContainers positioned in the most appropriate way, generally vertically, resting on the base of the crown in a structure similar to a rack, which favors axial alignment with the nozzle and facilitates the insertion of this inside the disposable tip ( and from the crown).
In the examples cited in Table 3 various mechanisms are used such as: a plate, a peripheral base and a peripheral skirt, where the plate contains the receptacles for the disposable tips, the base extends from the plate to a distal surface from where The protruding skirt is extended to allow similar trays to be fitted. A system with a transfer tray and a plate that pushes the disposable tips and releases them from the tray. A mounting for insertion of disposable tips that has an insertion surface on which the tips are placed and to which aretention force to insert the tips in one or more nozzles. A device for loading a container with disposable tips arranged in trays. The device inserts the tips placed one on top of another from its tray through a top platform that supports it and a lower platform or base that holds the container. The upper platform is pressed down to load the disposable tips into the container.
Ejection and replacement of disposable tips.
We define as "replacement" the process of insertion and expulsion of disposable tips, on and from the mouthpiece of the pipetting system, respectively. The disposable tip is inserted by first positioning the device above the disposable tip and aligning it with the nozzle in the axial direction, and then pushing the device or pipetting head over the opening of the crown of said disposable tip, while it remains inside the container or tray. When a disposable tip is inserted into the nozzle it is important that sufficient force is used to seal the joint, so that there are no leaks for the pressure variations that are made from the pressure chamber, inside the disposable tip, and that the fluid aspirated and dispensed does not escape through the nozzle / tip junction. In this way, it is achieved that exact quantities of fluid are aspirated and dispensed. Also the disposable tip must be mounted with enough force to prevent it from falling, but if it is mounted too hard it may be difficult to remove it from the end of the nozzle after use. Generally,Pipettes include a disposable tip remover (or ejecting system) consisting basically of a slidable cylinder, which surrounds the nozzle, in the axial direction of the disposable nozzle / tip assembly, and a spring that returns the cylinder to its initial position.
Various solutions have been developed to facilitate the ejection of disposable tips ranging from the implantation of mechanisms that push the tip to the push of a button, to designs of disposable tips that favor their deformation or are used in combination with specific designs of nozzles. Table 4 contemplates some examples of these cases, such as the design of a nozzle to reduce the force of insertion / expulsion that has lobes on which it seals the disposable tip when deforming when it comes in contact with them. These lobes have a particular shape in which their most prominent part is softened in the form of an upward ramp over the nozzle. We also find a nozzle and a disposable tip to decrease the ejection force, where the nozzle includes three sections, an upper one for securing the disposable tip, one intermediate that serves as a stop and one lower part for sealing. There is also a pipette in which the ejection of the disposable tip is not done from the outside of the mouthpiece as in most pipettes with ejector, which allows the radius of the mouthpiece does not increase and can be inserted pipette in narrow containers, this is achieved by placing inside the nozzle a device (piston type) that pushes the tip for ejection. Another case is a mechanism for ejecting disposable tips in which a sleeve around the nozzle is the one that, when pushed, expels thedisposable tip by storing the energy used to insert the disposable tip, which is achieved through a spring that when unzipped pushes the sleeve. This and the spring also serve to limit the insertion force. Another case is that of a nozzle with lateral support cylindrical areas on the outside that serve to adjust with cylindrical support regions inside the disposable tip to allow a simple but firm insertion of the disposable tip, while facilitating the expulsion. This nozzle defines an annular sealing zone and an annular support zone, where the sealing diameter is slightly greater than that of the support.
Pipetting method.
The pipetting operation is performed when a precise and relatively small amount of liquid is taken, this content remaining within a disposable tip. The liquid is introduced (dispensed) then into a second containeror distributed in several containers for analysis or some other type of testing or function, as in the case of dilution and / or mixing of liquids. The individual operation is also mentioned as aspirated / dispensed, due to the characteristics of the system responsible for carrying it out, and which uses a pressure chamber with a piston or plunger. Both volumes, aspirated and dispensed, are previously programmed by the user. The methods that can be found today in the bibliography are variants and modalities of a general method known for a long time, with which the following steps are fulfilled: a) positioning of the pipetting device above the container of disposable tips, aligning the nozzle in the axial direction with one of the disposable tips, carrying the device with the movement of the user's arm, holding it with one hand, or with a robotic arm,b) insertion of the nozzle inside the discarded tip, which is carried out by moving it in the axial direction, so that it enters through the crown while the discarding tip seats (from the crown) inside the container. A certain effort must be made in the axial direction to achieve an adequate seal between the nozzle and the inside of the disposable tip,c) by operating the pipetting device / tip discarded, the discarded tip inserted into the mouthpiece of the pipetting device is inserted inside the liquid to be transferred,d) a mechanical or electronic system performs and / or supervises the aspiration of the previously programmed liquid volume, which is done from the suction / dispensing subsystem,e) the disposable pipetting / tip assembly is moved so as to place the disposable tip in or on the container where a certain volume will be dispensed,f) the same mechanical or electronic system of step d) performs the operation of dispensing the volume of liquid, which can be repeated several times from step e) for several containers until the total volume of liquid aspirated and the disposable tip, inserted into the nozzle, becomes empty of liquid, g) moves the disposable tip / pipetting device assembly over a waste container, and then activates the disposable tip ejector so that it pushes the disposable tip out of the nozzle, and that it falls inside the container,h) If required, for the next sample or suction / dispensing operation, the process is repeated from step a).
This process, described for N = 1 channel (or mouthpiece), is basically the same for the case of NxM-channels (which is a multipipe). It also allows us to highlight the differences and novelties introduced in this invention from the point of view of the derived method.
In the references included in Table 5, variants of the general method of pipetting can be found (in relation to the placement of the disposable tip, sample aspiration, dispensing thereof and expulsion of the disposable tip), which are based on the introduction of sensors, devices, control loops or combinations thereof in one or more of the steps of the general methodof pipetting to, for example, ensure better precision, avoid contamination or make pipetting in microplates more flexible.
In cases where precision is sought, control loops with sensors (ultrasonic, piezoelectric, optical or pressure) are included to determine that the quantity aspirated is the desired one. In other cases, it is sought to ensure that all the aspirated liquid is expelled from inside the disposable tip, because sometimes some sample droplets remain attached to the walls of the same. To achieve this, sensors and additional steps are also used when pipettingthat a little air can be sucked (to generate pressure and increase the force with which the sample is ejected) or water (to increase the relative humidity within the disposable tip and reduce adhesion) prior to aspirating the sample. Finally, other methods involve disposable tip containers for automated equipment from which different sizes of tips can be taken and which in some cases allow aspirating or dispensing from selected positions of a microplate.
Manual pipetting system.
This type of system consists of a manual pipette and a container of disposable tips, where a good part of the operations are executed directly by the user. The pipettes can be mechanical, electronic or hybrid, they can also be simple (single nozzle) or multichannel (N nozzles, with N = 1, 2, ...). A recent example also shows that a head of NxM nozzles can be used manually by sliding on a coordinate table. There are several patents related to manual pipettes, in which new variants are proposed in their mechanisms and functionalities, as well as solutions to ergonomic problems, since they directly influence the health of the user. However, this does not only imply changes in the design but also in the structure of its internal mechanisms, functionalities, external form and materials.
In several of the existing pipettes, the user must also perform a force for the expulsion of the disposable tip already used. This force is in relationwith the corresponding insertion force, which is usually different for each user or depends on an adequate disposable tip and pipette positioning in the axial direction. In this process it is also necessary to make a movement of the arm that holds the pipette to position it on a container and insert the disposable tip. Because the process is often done repetitively, it influences the appearance of musculoskeletal damage to the user's arm, hand and joints. The force control applied when inserting a disposable tip into the nozzle depends primarily on the skill of the user. This means that an operator, inadvertently, could be using more effort than necessary. Then, even with an ergonomic tip ejection system, if this is operated with the fingers (for example the thumb), a force greater than that necessary to eject the disposable tip must be made. This can also lead to repetitive strain injuries. One option not recommended, because it can contaminate the disposable tip, is to insert the disposable tip with the other hand, but equally a force must be exerted and the tip may be badly positioned in the axial direction.
Since the internal mechanisms also develop the functions of aspiration and dispensing, it is sought that these do not offer great resistance in the operation by the user, and the forces involved for their operation are not very important when performing repetitive work.
Table 6 shows different examples of manual pipettes, among which are the different existing types (mechanical, electronic and hybrid). In all cases, characteristics thatthey present advantages for the users from the point of view of their operation, because they facilitate the calibration, diminish the possibility of errors on the part of the user and confer them greater number of programming options.
The examples in Table 6 contemplate the inclusion of methods for the correct calibration of the liquids dispensed, the inclusion of sensors in mechanical pipettes to be able to determine and adjust the amount of liquid aspirated, making it of the hybrid type since it incorporates electronic elements and feedback. , sensors in electronic pipettes to reduce the probabilities of error on the part of the users when choosing the suitable disposable tip, according to the selected volume, and the inclusion of communication with computers, to facilitate the interaction and programming by the user.
Automated pipetting systemIt is represented by teams where the participation of the user is minimal, intervening only for the programming of pipetting volumes, selection of number of samples and other additional less relevant functions. The execution of the pipetting process is carried out by a robotic equipment, which may be a coordinate axis or SCARA, on which a head is coupled with the components for the development of the functions. Even in this case the container with disposable tips is developed separately and, at most, is coupled in some way to the pipetting equipment. There is no example in which the container and the head of the pipetting equipment are coupled, so that they move together. The examples in Table 7 show that in the automated equipment the development focuses on the design of the heads that take the disposable tips and through which the tasks of aspiration and dispensing are carried out, emphasizing the increase in versatility and speed of the equipment. There are several examples in which heads are presented that can be easily exchanged to be able to adapt to different containers or arrays of microplates, from which the tasks of aspiration and dispensing are done, as well as equipment with a pair of heads where one is dedicated only to the aspirated and another to the dispensed. There are also teams in which up to three different heads are mounted for a better adaptation to the different sizes of microplates, and heads in which the work is not necessarily done by doing the aspiration and simultaneous dispensing in all tipsDisposable because they allow to choose personalized configurations. An example is also presented in which the nozzles that take the disposable tips allow the insertion of different sizes of disposable tips.
From the previous bibliography and the characteristics and properties that are usually considered for the current pipetting systems, the following conclusions can be obtained:1- there is no clear differentiation between the pipetting system and the pipetting device or equipment. For a better understanding regarding the aspectsintroduced in the present invention we have defined a pipetting system as the set composed of the device or equipment that performs the pipetting operations and the container or tray with disposable tips in its interior,2- no attempt has been made to modify the insertion method to change the manner of exerting force to insert the disposable tip into the pipetting device or equipment. This change in relation to the insertion force is difficult to achieve for mechanical systems in manual pipettes, although it is not very relevant in the case of automated equipment. But in this last case the method of inserting disposable tips can influence the better performance and speed of the equipment,3- there is a need to make the process of transferring disposable tips in a simpler way, facilitating the movements of the user and / or the speed of such process,4- the container is generally separated from the device or pipetting equipment, not having an interaction between them. This would imply the sum of new components and subsystems for the development of a greater number of functions,5- the container is at rest with respect to the pipetting device or equipment, which means that there is a certain number of movements that have not been optimized or decreased,6- there is no disposable tip insertion / ejection subsystem, allowing a homogenization of the insertion / ejection forces and a loweruser intervention in manual systems and parallel operations development for automated systems,7- Referring to the speed of the process, both manual and automatic, it can be easily verified that when the insertion and ejection of the disposable tip is made in parallel to the movement of the arm (of the user or robotic), time is saved in the process and then it gets more speed in the processing of the samples.
The foregoing, without being limited in any way only to those mentioned, are the properties and characteristics that constitute the basis of the novel aspects of the present invention. These aspects of the pipetting systems, which will be taken into account in the following sections, are mainly:1- It has two base structures, one that we call pipetting base, gives rise to the traditional components and subsystems found in the pipetting systems that are on the market, and another that we call coupling base, gives rise to the new subsystems introduced here. In a traditional pipetting system both structures are separate and never engage.2- A general system of hybrid pipetting is established, which is defined in three different levels: with terminal blocks (in a block diagram), with subsystems (in a schematic diagram) and with components and modules (in a device diagram) .3- From the above, different modalities and variants are derived to the pipetting system, since a large number of configurations and architectures can be conceived, and represents mechanical, electronic and hybrid cases.4- The configuration of an insertion / ejection subsystem is shown, which makes the replacement of disposable tips very efficient, achieving a minimum user intervention for a manual system or higher speed for an automated system. The refill is done in two different ways: with the nozzle moving towards the disposable tip or with the disposable tip moving towards the nozzle.5- Examples of manual pipetting systems are shown, for each case of the previous point, where disposable tip insertion / ejection subsystems are presented.6- It presents the possibility of having a double box with the disposable tips not used and disposable tips already used, to enable a fast and efficient recycling of the plastic from which the disposable tips and the box are made.7- What is mentioned in the previous points can be generalized to a system with NxM nozzles and also applied to the case of automated pipetting system, where a device with a robotic arm and a pipetting head of N x M channels (or nozzles) is used. .8- A system and a pipetting method applicable to the manual case and to the automated case are established.9- In the manual case, the relation of insertion and ejection forces is important from the ergonomic point of view.10- The problem of forces is not important in the case of automated equipment, since they have a robotic arm that replaces the user's arm. However, the way in which the box is located with disposable tips and the movements that the head must make also influence the speed of the equipment to carry out the process.
BRIEF DESCRIPTION OF THE FIGURESFig. 1 is a block diagram of the hybrid pipetting system, showing the terminal blocks, which give rise to the different subsystems, being able to connect in different ways or sharing intermediate blocks, which are inside the central block (20) . The external components are also highlighted: the nozzle (11), for the pipetting operation, the disposable tip (12) inserted at its end and the box (13) with disposable tips, having in its interior: the assembly (14) and the disposable tip removed (15).
Fig. 2a is a schematic diagram of the disposable tip insert / ejection subsystem for mobile nozzle, where the nozzle (11) moves towards the position (11 A), above the box (13) with disposable tips, for insert one of them at its end.
Fig. 2b is a schematic diagram of the disposable tip insert / ejection subsystem for fixed nozzle, where the disposable tip (15) of the box (13) is taken by the insert module (46), in position (46A) ), and is carried to the end of the nozzle (11) and inserted into it in the position (46B).
Fig. 3 is a flow diagram showing the steps to be followed for the pipetting operation using the hybrid pipetting system of Fig. 1.
Fig. 4a is a schematic representation of a hybrid manual pipetting device, with axial symmetry, where the disposable tip insertion / ejection subsystem and the box (76) for the mobile nozzle case can be seen. Here a cut is shown at the average height on the three-dimensional structure of the device, seen from the R point of viewFig. 4b shows the movement of the nozzle (78) to insert a disposable tip thereon from the box (76), in the case of the device of Fig. 4a. Fig. 5a is a schematic representation of hybrid manual pipetting device, with axial symmetry, showing the disposable tip insert / ejection subsystem and the box (76) for the case of fixed nozzle. As in Figs. 4a and 4b, on this device a cut is made at the average height of the three-dimensional structure, to see the internal components when you have the point of view R. On the right you can see the extension of the sector with dotted line on the device .
Fig. 5b shows how the ejection of the disposable tip (79) inserted in the nozzle is done for the pipetting system presented in Fig. 5a.
In Fig. 5c is shown the manner in which a disposable tip is brought from the box (76) to the end of the nozzle (18) and inserted therein, following the ejection step shown in Fig. 5b.
Fig. 5d shows the manner in which the insertion / ejection subsystem is released to return to its initial position, following the step shown in Fig. 5c.
Fig. 6a is a block diagram of an extreme case, for the hybrid pipetting system of Fig. 1, where it is shown that the terminal blocks (5B), (8), (9) and (10B), introduced in the present invention, they are within the structure (C).
Fig. 6b is a block diagram of an extreme case, for the hybrid pipetting system of Fig. 1, where it is shown that the terminal blocks (5B), (8),(9) and (10B), introduced in the present invention, are within the structure (D).
Fig. 7 is a block diagram of the hybrid pipetting system with a double box with sections (13A) and (13B), containing the disposable tips to be inserted on the end of the nozzle (11) and the disposable tips already used respectively, so that the ejection subsystem has been replaced by a disposal / recycling subsystem of disposable tips, with terminal block (3A).
Fig. 7a is an enlargement (corresponding to Fig. 7) of the coupling sector between the structures (D) and (C), according to the cut AA 'indicated in Fig. 7, so that it can be seen with better detail the terminal blocks and their ligatures.
Fig. 8a is a schematic diagram of the disposable tip insert / ejection subsystem for mobile nozzle with a double box (as in Fig. 7), where the nozzle (11) moves towards the box section (13A) , which contains unused disposable tips, for inserting one of them at the end of the nozzle (11), and after having performed the aspiration / dispensing operation moves towards the box section (13B) for discarding the disposable tip (12).
Fig. 8b is a schematic diagram of the disposable tip insert / ejection subsystem for fixed nozzle with a double box, where the disposable tip (12) which is inserted in the nozzle (1) is brought by a mobile insertion module (Fig. 154) from the position (154A) in the box section (13A), which subsequently inthe position (154B) separates the disposable tip (12) from the nozzle (11) and brings it to the position (154C) in the box section (13B) for discarding the disposable tip (12).
DETAILED DESCRIPTION OF THE INVENTIONFrom the definitions given in the previous section (Introduction and Background) it can be concluded that a system is defined at least in three levels: block diagram (level 1), where functions are defined, schematic diagram (level 2), where define the subsystems, and device diagram (level 3), where the components are defined. The definition at level 1 is the most general, and it can be said that it is unique in the sense that the variants it supports are the possible architect that we will define, which influence various properties of the pipetting system but do not influence the functions it performs. . For level 2 the variants are many more, since the subsystems can be grouped among them or constituted in many ways, and this gives many more possibilities in the structof the pipetting system and its operation. In level 3, since the same functions and the subsystems themselves can be made up of different types of components, there are still more variants and architect.
The present invention relates to a hybrid pipetting system that is internally constituted by different subsystems, which are responsible for fulfilling the functions and develop the corresponding operations. Some of these subsystems are present in traditional pipetting systems, and can be found in equipment and devices that are on the market, but other subsystems have not been contemplated (in the patent literat nor are they present in them, and are introduced in this invention. In what follows, we will make a clear distinction between the twoclasses of subsystems (the already known ones and the new ones), so that the novel contributions presented here can be clearly seen.
In Fig. 1 the block diagram of a pipetting system can be observed, which includes in its representation the special cases of the manual and automated systems. There are two struct (D) and (C), which constitute the bases that support (directly or indirectly) the components of the complete pipetting system. The first concept introduced here is that both struct are separate but can be coupled and uncoupled from each other. The outer shape of each one is not defined in Fig. 1, since they can be very varied and made of different materials, depending on the type of pipetting system (manual or automatic), ergonomics, number of functions which is intended to include, the performance to be achieved and the design that you want to present. The struct(D) is called pipetting base, since it contains mostly the terminal blocks that give rise to the traditional subsystems that are in a pipetting system, while the struct(C), which contains the majority of the terminal blocks that originate the new subsystems (or a good part of them), we denominate base of coupling. In a traditional pipetting system, both struct are separate and never engage with the struct(C), which includes the box (13) with disposable tips (which may or may not be sterilized), at rest with respect to the struct(D), and both move together.
For a better understanding of the fig that we present, we introduce some general definitions in relation to the block diagram of the pipetting system of Fig. 1:1- Central block: it is a single block that replaces a whole set of blocks and connections that are not defined, since there may be a large number of possible architectures. In some ways it is similar to a black box for the hybrid pipetting system, and receives the connections from the terminal blocks. That is, it is not defined in its structure but it is defined in its function, which is to concentrate the interactions between the terminal blocks. It helps to establish a general structure of pipetting system, from which particular cases can be derived.2- Terminal block: is one that has at least one connection with the central block, having in its interior interaction with other terminal blocks, as well as an external interaction or a link to an external component. Each terminal block defines a function of the pipetting system, and from there the subsystems that integrate it and the type of components they include are derived.3- Intermediate block: it is the one that has at least one input from and one output to another block as part of a subsystem, and serves to define an architecture in the pipetting system, establishing the way in which terminal blocks are connected or related , and finally if the pipetting system is manual, automatic or semi-automatic, as well as whether it is mechanical, electronic or hybrid.4- Isolated block: it is the one that is disconnected from the central block and the rest of the terminal blocks, also fulfilling the function that corresponds to it.5- Connection between blocks: links are established between blocks that also have a direction (with arrows) to know where the movement or functions of the constituents of a subsystem are going. All connections established between two or more modules, between two or more components or between modules and components can be electrical, electronic, mechanical, acoustic, pneumatic, optical, electromagnetic or hybrid among the above.6- Ligation from a terminal block: it is an idealized representation to show that there is an interaction between a terminal block and an external component. The interaction can finally occur through one of the components of the terminal block that develops the specific function of ligature or a direct coupling with the set of components within the terminal block.7- Gate over a ligature or connection: it allows specifying, for a certain architecture, if such ligature or connection is present (closed door) or not present (open door), although it is always shown (in the figures) as open. This affects the number of functions, the connectivity and finally the type of device, which can be mechanical, electronic or hybrid, as well as manual, automatic or semi-automatic.8- External component: is one on which one or more outputs (by means of ligatures) are applied to the terminal blocks and subsystems thatcompose (at different levels) the pipetting system. It is coupled in some way to structures (C) and (D) or to another external component. In general, there is more than one subsystem (although this is not necessarily determinative) that act on or interact with an external component.9- External interaction: It is the one that takes place between a terminal block and the user or with some equipment, device, component that is not coupled to the structures (C) or (D). Such a device or device may also have a means of connection or communication that allows it to perform said interaction10- Internal interaction: it is given by the connections between blocks, modules and / or components and allows the definition of the subsystems in different levels.1 1 - Additional device: attached as part of a terminal block acting on an external component and in the corresponding ligature, and serves to assist the terminal block in its function. The additional devices that we use here are sensors and couplings, and can have a continuous or discontinuous connection to a terminal block.12 - Sensor: is a device that detects physical or chemical magnitudes, called instrumentation variables, transform them into electrical variables and transmit them to a control subsystem. A sensor can be resistive, inductive, capacitive, magnetic, electronic, mechanical, optical, acoustic or hybrid among the above.13- Coupling: Component that serves to group, join or fit two or more structures, components or modules, so that they fit perfectly andCombined operation produces a convenient result. It can be magnetic, mechanical, electronic, electromechanical or hybrid among the above. When we speak of a subsystem, we must mention that they have certain characteristics typical of the general definition of systems plus other characteristics, which they have since they are a subset of a larger set for the three levels in which a system can be defined. All these characteristics are:1) that have structure and form, defined by the modules and / or components, their connections, their composition and the space required for the movements they must develop,2) that have behavior, involving inputs, processing, interaction with other subsystems, and outputs of matter, energy, information or data,3) that have interconnectivity, since the various parts of the subsystem have a functional and structural relationship between them, from the central block and the specification of intermediate blocks (level 1) or from the connections and interactions between the blocks that have a set of components, individual components and modules (levels 2 and 3),4) that can have functions or group of functions, through their outputs and interactions, which are defined from the inclusion of terminal blocks in the general design of the pipetting system and then specified by the components and modules,5) that different elements can be shared between different subsystems, which in a block diagram correspond to intermediate blocks and in theschematic and device diagrams correspond to component assemblies or modules located in an intermediate position,6) that each subsystem is differentiated through the function or action performed by its terminal block, which may include a component, a set of components or modules.
Characteristics 1) to 4) are common to all systems and subsystems, but the remaining two are especially specific to subsystems considering their direct application to the pipetting system of the present invention. Characteristics 5) and 6) arise from specifying where the terminal blocks point to and how the blocks or intermediate components are integrated, towards the possible inputs or outputs of each subsystem, which have to do with external components and with internal or external interactions .
It can be seen in Fig. 1, and from the definitions given above, that each block has a function and represents a set of components or modules; comprising a central block, intermediate blocks and terminal blocks, as well as their connections. Then, we see that the pipetting system consists of a central block (20) and several terminal blocks, numbered from (1) to (9), (10A) and (10B). The terminal blocks (1) (2) and (7) are used for interaction with the exterior, and for that reason part of them is outside the structure (D). The remaining terminal blocks interact by ligatures, numbered from (21) to (32), with the external components that are: the nozzle (1 1), which sits on the base (D) and exits towards the outside, the disposable tip inserted at its end (12), which interacts directly with the liquid to be poured, the box (13),with disposable tips inside, the couplings (16), which are always attached to the box (3) or are part of it, the set of disposable tips (14), inside the box, the detachable disposable tip (15) of the previous assembly and the sector of the base structures (C) and (D) on which the coupling is made by the box coupling block (8). All the disposable tips mentioned can be classified as external consumable components. Ligatures and connections have the following characteristics:• can be continuous or discontinuous, either by the movements of components within each terminal block or by the type of coordination they should have between them,• represent interactions of some kind or are a direct action of a component of the corresponding terminal block on an external component, both of which can act with additional devices such as sensors,• from a terminal block more than one ligature can come out, and this means that it develops a function that is part of a composite function or a combination of functions, and in that case on some or all of the ligatures there can be a door that allows the option if that function, which is part of the composite function, is included (closed door) or not included (open door).
Within the central block (20) are not defined the intermediate blocks or the connections and interactions with the terminal blocks, nor the connections between them. This central block (20) is then undefined in its compositioninternal, and this is because within it there may be a large number of possibilities in terms of connections to and from the terminal blocks and in the connected intermediate blocks, which are fundamentally those within said central block (20). The characteristics and importance of this central block (20) are the following:1. Its function is to concentrate and enable interactions and communications between terminal blocks,2. it is undefined in the sense that, through the specification of the connections and the intermediate blocks that are inside it, an architecture of the hybrid pipetting system is established,3. When defining the architecture, the way in which the terminal blocks and the intermediate blocks are joined or interacted is also specified (at level 1, very general) the possible subsystems that they can form. In any case, as has been stated before, subsystems with a better detail and specification are defined from level 2.
Structurally, we also see that there are two characteristic angles ß and a, with respect to the main direction DP (axial direction of the pipetting system), which define the pipetting direction DB and the insertion direction Dc. The first direction (DB) characterizes the pipetting system in terms of its symmetry, ie whether it is axial (ß = 0) or non-axial (ß? 0), and is a well-known aspect. The second direction (Dc) is a novel aspect and is the one corresponding to the axial direction of the trapped disposable tip (15) inside the box (13).
In a first point of view each terminal block defines a subsystem, so that the essence of the subsystems included in the pipetting system and the most relevant that allows distinguishing them from one another are the terminal blocks, which develop a certain function. In this way, each of the terminal blocks of Fig. 1, numbered from (1) to (10A) and (10B), defines, through its same name, a subsystem of which they are the output or the input. At a later level, a subsystem is defined by the last set of components or modules that act directly on an external component or that perform an external interaction, without considering any additional device.
In Fig. 1 we have the following terminal blocks: interaction with the user (1), communication and interconnection (2), disposable tip ejection (3), aspiration / dispensing (4), angular nozzle positioning (5A), nozzle movement (5B), data processing (6), power and power (7), box coupling (8), location / section of disposable tips (9), nozzle / tip fitting (10A), tip insert disposable (10B).
The terminal blocks have the following characteristics:1- some are essential, and can not be missing, and are the following: interaction with the user (1), disposable tip ejection (3), aspirated / dispensed(4), and adjustment of nozzle / disposable tip (10A),2- the rest can be present (all or only some), allowing to define the pipetting system from two points of view: first if it is manual or automatic, second is mechanical, electronic or hybrid,3 - are associated with each of the functions or operations that can be performed, act on an external component or interact with the outside, establishing the outputs and / or inputs of the subsystems they define, as well as the interaction between them or with some intermediate block inside the central block (20),4- the components of the terminal and intermediate blocks, are electronic, mechanical, pneumatic, optical, magnetic, electromagnetic, acoustic and / or hybrid between some of the above,From Fig. 1, and since each terminal block allows defining a subsystem, some characteristics can be obtained with respect to the possible inputs and / or outputs of the subsystems, which point to:1) interaction with the outside, defined by the terminal blocks of interaction with the user (1), communication and interconnection (2) and energy and power (7),2) internal interaction with other subsystems, which is represented by the double-direction arrow of each block (except the terminal block of energy and power (7) that has it in only one direction),3) interaction with the nozzle (11), which are represented by the ligatures (21) (24A), (24B), (24C), (25), (26) and (27), and the sensor (17A) with the ligature (22) respectively,4) actuation on the disposable tip (12) or on the assembly that forms this with the nozzle (11), through the ligatures (21), (26) and (27),5) interaction with the couplings (16) of the box (13), by means of the ligature (32),6) interaction with the set of disposable tips (14) inside the box (13), through the ligatures (29A) and (29B),7) interaction with the selected disposable tip (15) from the assembly (14) by ligatures (28), (29B) and the sensor (17B) of the ligature (23),8) coupling to the base structures (C) and (D), through the ligatures (30) and (31), with the couplings (19A) and (19B).
These types of action or interaction contain the aforementioned characteristics 1) to 6) for the subsystems, and completely define each subsystem, since within the central block (20) the intermediate blocks and connections can occur in a way that is not determined in Fig. 1, and there may be a very large number of possible combinations. However, as already mentioned, the function of the central block (20) is clearly established and we can define each subsystem based on the characteristics of the terminal block, which has a set of components or modules in charge of the inputs / outputs. of each subsystem (from the aforementioned list). All the terminal blocks are connected to the central block (20), but we must note that only the terminal block of power and power (7) has connection in a direction of reception and not signal sending, ie the interaction is only given in the entry direction. The terminal blocks of box coupling (8), location / section of disposable tips (9) and disposable tip insertion (10B) are located between the base structures (D) and (C), and then the set of components or modules of these terminal blocks are distributed between both structures according to the architectureproper to the corresponding subsystem. This means that there is a change in the concept of disposable tip container that is now equivalent to the coupling base (C), and it is no longer just the box with disposable tips but it can have some components within its structure, which they are also coupled to some components that are based on pipetting (D), as long as they are part of the same terminal block. We also note that the terminal box coupling block (8) is in charge of the coupling between the structures (D), (C) and the box (13), through the couplings (19A), with the ligature (30) , and (19B), with the ligature (31), and with the ligature (32) towards the couplings (16). It has two doors P1 and P2, which means that with the doors closed the terminal block (8) is connected to the central block (20) and to the coupling structure (C), and with the doors open it is independent of both. However, it is necessary that at least there be coupling between the base structure (D) and the box (13).
It is still necessary to specify the manner in which the disposable tip (15) becomes inserted in the nozzle (11), becoming the disposable tip (12) that is ready for the operation of aspirating / dispensing. The pipetting system can be a mobile nozzle, when the nozzle (11) goes towards the disposable tip (15), and then it is inserted at the end of the nozzle (11), or it can be a fixed nozzle, when there is a subsystem that carries the disposable tip (15) towards the mouthpiece (11) and is responsible for inserting it. Then, there is a gate P3, on the ligature (26) of the terminal block insertion tip disposable (10B), because it is representing the two options mentioned for the nozzle (11): that is mobile(open door) or fixed (closed door). The insertion angle (a) mentioned above, according to whether the pipetting system is mobile or fixed nozzle, can also be interpreted in two ways:1. it establishes the angle at which the nozzle (11) must be positioned above the disposable tip (15) so that it can be inserted at its end (movable nozzle), just as the disposable tip (12) is located,2. it is the angle at which the module or components that are inside the terminal insertion block (10B) must position, and which take charge of the disposable tip (15), and then take it up and insert it at the end of the mouthpiece (11). ) (fixed nozzle).
The displacements of the nozzle (11) take place from two terminal blocks: angular positioning (5A) and nozzle movement (5B). The angular positioning (5A) is known, and is an ergonomic property, given by the ligature (24B) and can be an isolated block if the door P10 is open. In the case of the terminal block of movement (5B), there are two doors P6 and P7, both of which can be closed, indicating that the functions of the nozzle movement (11) are in the axial direction by means of P6 and the ligature (24C). ), as well as movement of the nozzle (11) towards the box (13), with closed P7 and ligature (24A), being in such a case a mobile nozzle pipetting system (P3 open).
The nozzle tip / tip fitting block (10A) acts with tie (27) and has the gate P4 to indicate that when closed it can be part of a subsystem and when it is open it can be only one module orfixing component between the nozzle (11) and the disposable tip (12) which is isolated from the central block (20). The same happens with the terminal block for the location / section of disposable tips (9), through the door P5 (isolated when it is open).
We see that in Fig. 1 the pipetting system is defined at a general level, and this means that it represents the totality of functions that can be developed. But the architecture, that is, the structure of intermediate blocks and the connections defining the subsystems, is not established in Fig. 1. That is, the way in which the intermediate blocks interact with each other, within the central block (20), and towards terminal blocks, this being what defines an architecture of the pipetting system. It is clear then that, in the block diagram of Fig. 1, the terminal blocks are the most important since they define the development of the functions and operations of the pipetting system, and that at this level 1 the subsystems are defined with the set of intermediate blocks, terminal blocks and connections. In levels 2 and 3 within each of these terminal blocks we can find components, sets or groups of components and / or modules, which can be of the types mentioned above.
Below we give a brief explanation of the known subsystems associated with the corresponding terminal blocks, which are traditionally part of a pipetting system, without thereby being limited (in any way) to them.
• Subsystem of interaction with the user, on the terminal block (1): From here, the functions of the pipetting system are programmed, the volumes of liquid aspiration / dispensing are established and / or some of the operations are executed and controlled. The user can operate the pipetting system interacting with the terminal block (1) manually (mechanical or electronic), both for the development of the functions and for programming them. This subsystem can be activated by manually operated buttons or levers, with mechanical, pneumatic, electronic or electromagnetic transmissions, by a drive through the user's voice or by remote action control. In Fig. 1 we see that the terminal block (1) has a two-way connection with the central block (20), interacting in its interior with other subsystems. The subsystem of interaction with the user is, in some way, present in all known systems and is necessary to be able to indicate to the device the operations to be performed and obtain the results.
· Communication and interconnection subsystem, on the terminal block (2): It allows the interaction of the pipetting system with other equipment, or with some other type of device. You can use wireless communication means (bluetooth, WLAN, infrared, radiofrequency), communication interfaces with peripheral devices through cables or ports such as USB to a computer or control console and data processing, without being limited to these cases. In Fig. 1 it is also seen that the communication and interconnection terminal block (2) interacts and connects with other systems within the central block (20). Eastsubsystem is present in some cases of electronic and hybrid pipetting systems, or in automated equipment, being especially suitable in the latter case to coordinate the work of different equipment in the laboratory.
• Disposable tip ejection subsystem, on the terminal block (3): The ejection of the disposable tip (12), inserted at the end of the nozzle(11), it is done once it has been used in order to be discarded and to avoid contamination between different samples. Most of the pipetting systems that currently exist have an ejection subsystem consisting of a hollow tube that is located outside the nozzle (11), so that it can rise and fall in relation to it, and its purpose is to transmit the force (that the user or the equipment exerts) to expel the disposable tip (12). Although most of the ejection subsystems are mechanical, they exist of another type such as the pneumatic or electronic case. Automated pipetting systems have no problems in terms of the force involved in the ejection, but they develop the same process as the manual case. In Fig. 1 the disposable tip ejection terminal block (3) has a two-way connection to the central block(20), and acts directly towards the disposable tip (12) by ligature(twenty-one) . All pipetting systems have an ejection subsystem, some interesting variants having appeared in recent years regarding the type of components used.
• Aspiration / dispensing subsystem, on the terminal block (4): Through it the pipetting devices carry out their essential function, which is thetransfer of liquids between different containers, vessels or containers. This is, by suction or aspiration of a liquid in a precise manner, according to a volume previously determined by the user, which is then dispensed (all in parts) with the same volumetric precision in another container (s). This subsystem is usually composed of a piston that moves air inside a pressure chamber, driven by a motor or manually, transmitting pressure changes to the inside of the disposable tip. The intermediate component that allows connecting the pressure chamber and the disposable tip is the nozzle (11), is located at a certain angle ß with respect to the axial direction and allows to define the pipetting system as axial (ß = 0) and non-axial (ß? 0). The nozzle is a plastic tube, but without being limited, with an inner channel in its axial direction, through which the mentioned connection is established (between pressure chamber and disposable tip). But it can also be that the disposable tips are replaced (for certain applications) by micro syringes, which have internally a plunger. The suction / dispensing terminal block (4) has a two-way connection with the central block (20) and interacts directly with the nozzle (11) by means of the ligature (25). This way of dispensing liquids is the most efficient in relation to the volumes involved, so pipettes are usually classified as piston pipettes, although when it comes to dispensing drops accurately they are no longer as effective.
• Subsystem for control and data processing, on the terminal block (6): In order to carry out the functions performed by the different subsystems, such as suction / dispensing, insertion / ejection of disposable tip, data exchange, drive, processing and control in general, a subsystem that receives as input the signals generated by the remaining subsystems and by the sensors, to process them and generate outputs that regulate and perform the functions necessary for the proper functioning of the pipetting system. This subsystem contains an electronic processor and a memory, and concentrates all the input signals (suction / dispensing volume, position of the disposable tip and nozzle, state of the signal for ejection and disposable tip replacement, etc.). generate actions accordingly: suction of liquid, dispensing of liquid, replacement (insertion and expulsion) of the disposable tip (12), variation of the volume of aspirated / dispensed, among others. From the control and data processing terminal block (6) there is interaction with the remaining subsystems through the connections within the central block (20) and receives as a data the position of the nozzle (11) and the disposable tip (15). ) by sensors (17A) and (17B), with ligatures (22) and (23). The control and data processing subsystem may not be present in the pipetting system, and in this case it is of the manual mechanical type, but when it is present it may be electronic or hybrid, as well as manual or automatic. This subsystem is not found in mechanical manual devices, although since the tendency is to hybridizePipetting systems, this subsystem is being incorporated into many of the already known.
• Subsystem of energy and power, on the terminal block (7): Through this, the energy and power necessary for the operation of the other subsystems is provided, as well as for the operation of the sensors and couplings involved in the operation of the pipette. The energy and power subsystem has a rechargeable battery, passive and active electronic components, and a connection with input from the power grid, solar cells or another type of power source that can be used for recharging. Obviously, due to its characteristics, it is not present in fully mechanical pipetting systems.
• Adjustment subsystem between the nozzle (11) and the disposable tip (12), on the terminal block (10A): In the tables with references to patents, especially Table 4, it can be verified that there is much done in relation to the nozzle / tip attachment. For this, the mouthpiece (11) usually has a frustoconical end at its distal end to facilitate the insertion of the disposable tip. To further promote the sealing nozzle / tip disposable or facilitate the expulsion of it, you can use o-rings, components or elastic walls or various materials with deformation properties, pneumatic components, improvement in the materials from which they are made disposable tip and nozzle, components for threading the nozzle on the disposable tip, without for that reason being limited in any way to this list. A better performance is achieved in the grip by friction or in the sealing between bothcomponents as well as less force in the ejection, since we must emphasize that there is a relationship between the forces of insertion and expulsion that then establishes a relationship between both subsystems and makes the final performance of the device or pipetting equipment. The terminal block for adjusting the nozzle / disposable tip (10A) acts through the ligature (27) and may not be connected to the remaining blocks, forming an isolated subsystem, when the door P4 is open. The adjustment or sealing between the nozzle (11) and the disposable tip (12) is present in all pipetting systems, with different variants and levels of complexity.
· Angular positioning subsystem of the nozzle (1), on the terminal block (5A): When the pipetting system is axial it has the angle ß = 0 that is fixed, but when it is non-axial ß? 0 and can take any value between 0 and 90 degrees. There are some manual systems that have certain angular positions, so that the angle ß can be varied at the user's discretion. This is important as ergonomic property. In an automated pipetting system, it is a function that can be set automatically for each individual aspiration / dispensing operation. In the pipetting system of Fig. 1, the variable angular position is represented from the terminal block (5A), through the ligature (24B). As seen in Fig. 1 it is connected to the remaining subsystems but it can also be isolated from the central block (20) if the door P10 is open. So, we see that this subsystem can be used not onlyin manual systems but also automatic, and from this point of view also has a degree of originality introduced in the present invention.
These subsystems have the property of characterizing the type of pipetting system, according to the nature of their components, and some or all may be present (as already mentioned for the terminal blocks), so that the pipetting system can be mechanical, electronic or hybrid. In addition, from another point of view it can be manual or automatic, or even semiautomatic. That is, Fig. 1 contemplates all the possibilities and variants of a pipetting system as it is conceived today, and other additional considerations that are the object of this invention, and which are also presented as subsystems. The subsystems that we introduce here and present as part of a hybrid pipetting system, but that can also be (as special cases) mechanical or electronic, are:• Nozzle movement subsystem, on the terminal block (5B): To perform the replacement of a disposable tip in a semi-automated or automated manner, it is necessary to have a subsystem that inserts, in some way, a disposable tip from a container at the end of the nozzle (11). This can be done by moving the disposable tip (15) towards the nozzle (11) (fixed nozzle) or by moving the nozzle (11) toward the disposable tip (15) (mobile nozzle). The subsystem described here considers the second possibility, since it establishes a movement of the nozzle (11) towards a suitable position above the disposable tip (15). This is represented by the ligature (24A) with the gate P7 closed. That is, the nozzle (11) is carried by the blockmovement terminal (5B), or some of its components, developing movements of rotation and / or translation that allow it to be located above the disposable tip (15), aligning both axially, to insert it at the end of the mouthpiece ( eleven). Since there is another possibility, moving the disposable tip (15) towards the nozzle (11), being fixed in this case, is that the gate P7 is included that allows enabling or disabling the ligature (24A) of the terminal block (5B). But also the nozzle (11), through this subsystem, can have a movement in the axial direction to facilitate insertion and ejection of the disposable tip (12). This movement can be present for both movable nozzle and fixed nozzle, and is given by the ligature (24C) with the gate P6 closed. The subsystem with nozzle movement is not present in any type of pipetting system. Although it can be said that the automatic pipetting systems have movement of the nozzle (11), this is due to the movement of the head and there is no movement of the nozzle in the reference system fixed to the head.
• Subsystem of box coupling, on the terminal block (8): It consists of flexible locks, plastic material, magnetic, electromagnetic couplings or mechanical hooks that allow to firmly support the base structures (C) and (D) between them and the box (13) about them. In known systems, the cage is separated from the pipetting device or head, and the disposable tips therein are kept in position so that they can be inserted in the simplest manner on the end of the nozzle of the pipetting device or head. But in the present case the box with disposable tips is partof the coupling base (C), or container, and can be coupled and uncoupled in a simple manner either the single box of both bases or the box together with the coupling base (C) of the pipetting base (D). The important thing is that at least the box (13) can be easily removed to be replaced or reloaded with other disposable tips inside. In Fig. 1 it is seen that from the terminal block (8) the ligature (32) goes directly on the couplings (16) attached to the box (13), but also has a ligature (31) with the door P2, which it makes it optional, on the structure (C) and another ligature (30) on the basis of pipetting (D), acting through the couplings (19A) and (19B). Gate P1 (when open) indicates that this terminal block can by itself form the coupling subsystem and have no connections with the central block. This subsystem is not present in the current pipetting devices.
• Subsystem of location / section of disposable tips, on the terminal block (9): It has connection with the central block (20) to coordinate the movements of the set of disposable tips (14), located inside the box (13) ), with other functions and operations of the pipetting system. It can also be isolated from the other subsystems, through the open gate P5, since it can be a subsystem similar to a bullet magazine. In this way some functions can be developed in parallel. The terminal block (9) acts on the set of disposable tips, guiding the assembly through the ligature (29A) so that one of the disposable tips is placed in position to be set apart from the rest and aids in the separation of the disposable tip (15). ) by ligature (29B). In current systems the arrangement of the tipsDisposable is static, that is to say that they do not have a positioning inside the box, so this type of subsystem is not present.
• Disposable tip insert subsystem, on the terminal block (10B): This subsystem facilitates the insertion of disposable tips, such as (12), at the end of the nozzle (11) of the pipetting system. The function of these disposable tips is to avoid contamination by carry between different samples. This subsystem is directly related to the nozzle tip / disposable tip subsystem, defined by the terminal block (10A), of which there are several today. In the insertion of the disposable tip (15) on the nozzle (11) it must be ensured that the disposable tip (15) is inserted with sufficient force to guarantee a seal that ensures the precision of the volume of aspirated and dispensed, but that a at the same time, the user demands (in the case of a manual system) the least possible force to perform the ejection of the disposable tip, that is, that there is also a relationship with the disposable tip ejection subsystem, defined by the terminal block (3). ). Until now, the insertion of the disposable tips in the manual pipetting devices is performed by the user, and the force exerted for the insertion is not controlled and only depends on the experience, expertise and perception of the user. With this subsystem the process is done with a minimum and homogeneous force, for each disposable tip (ergonomic property). In the case of automated equipment, since it performs the same movements as in the manual case, the head must insert a disposable tip over the nozzle (11), prior to the aspiration / dispensing operation. With this insertion subsystem, we intend to carry out thisParallel task in order to give greater speed to the pipetting equipment, which is generally used when there are many samples. In Fig. 1 the terminal block (10B), which has a direct relationship with the terminal block (5B), represents the option that the disposable tip (15) is moved to the end of the nozzle (11) and inserted in this. This is manifested by the ligature (26), which for this reason has a gate P3 that can be closed in case the gate P7 is open, but obviously can not both be closed or open. The other ligature (28), from the terminal block (10B), goes towards the disposable tip (15) since also the subsystem is responsible for exerting the appropriate force in the direction of insertion on the nozzle (11), either for Fixed nozzle as mobile. This subsystem is not present in the current pipetting systems.
• The control subsystem also has extended functions since it intervenes in the movement of the nozzle, the disposable tip location, communication and interaction, as well as controlling the positions of the moving elements such as the nozzle (11) and the disposable tips, which is done through the sensors (17A) and (17B), from the ligatures (22) and (23) respectively. All of these are functions of the new terminal blocks introduced in the present invention.
As already mentioned, all these subsystems act directly or indirectly on the nozzle (11) and the disposable tip (12) that is located at its end, but some also act on the box (13) and on the disposable tip (15) , as well as with the couplings (16). They also interact with the outside and,internally to the central block (20), they interact with each other (if none is isolated). In addition to the subsystems mentioned there are two important components with innovative aspects within the scheme of Fig. 1: the box coupled to the entire system and the mobile nozzle, which are called external components, since they do not belong to a single subsystem. The novel aspects in relation to them are:• There are two base structures (D) and (C) that can be attached to each other: The pipetting base (D) can be identified with what is now the manual pipette or the pipetting head in automated equipment, whereas the coupling base (C) is the container of disposable tips, which is separate from the previous ones. By being able to fit (D) and (C), a more complete and more complex system is formed than those that currently exist. In addition, the container concept is different since it may also include terminal block parts of the subsystems and a box (13) with disposable tips.
«There is a movement nozzle (mobile nozzle) or an insert module with transfer of the disposable tip (fixed nozzle). These are the two options that exist so that a new disposable tip can be inserted at the end of the nozzle (11), and this will be seen in more detail in the examples of Figs. 2a and 2b. Likewise, if the nozzle (11) has several angular positions (fixed ß in each operation of aspiration / dispensing) it is the same case of a fixed nozzle. In the mobile case, the nozzle can be moved with rotations (on an axis or on a point) and / or translations in space, driven by components or modules located inthe inside of the pipetting and coupling bases, to be positioned from there above one of the disposable tips that are inside the box (13). • A box (13) with disposable tips is included within the base structure (C), which can be attached to the base structure (D), directly or through the base structure (C). This box is the equivalent to the container (rack in English) of today, and there is also the possibility that the box (13) remains separate from the pipetting base as it occurs in such cases.
Now we must consider certain important aspects regarding the system shown in Fig. 1:1) at level 1, when the block diagram is defined, the subsystems mentioned above are characterized by the terminal block that interacts directly in relation to the function developed by the subsystem, with an external component or with the external one. This point of view is not strict or determinant, since different subsystems can be taken according to the interaction of the components and modules within the intermediate blocks involved. That is to say, when you go to levels 2 and 3, two or more subsystems (as they were previously considered) have components in common, except for some components or modules corresponding to the terminal block, they can be included in a more general subsystem and more complete that includes them.2) We use a different point of view from what is normally used, since for example, the subsystem of interaction with the user must be connected to the other subsystems that exert action on an external component or with thecontrol subsystem, and even the latter is also connected to the corresponding terminal block of any of the remaining subsystems. This makes a subsystem more complex in its definition at level 2 and 3, and is not characterized only by its terminal blocks. But the concept here is different, since the subsystem is complete if from the same component of the subsystem of interaction with the user different actions can be executed (corresponding to different terminal blocks), then the most general subsystem involves more than one terminal block , since it has an intermediate block that allows linking them.
EXAMPLES WITH A SCHEMATIC DIAGRAM.
The two above aspects are considered in Figs. 2a and 2b, where two different schematic diagrams for an insertion / ejection subsystem can be observed that contemplate the two possible ways of introducing a new disposable tip at the end of the nozzle (11). As already mentioned, this can be done by positioning the nozzle (11), as indicated in Fig. 2a, over the disposable tip (15) and inserting it over the (mobile nozzle case) or carrying the disposable tip ( 15) towards the end of the nozzle (11) and inserting it into it, as shown in Fig. 2b (case of fixed nozzle). In both figures the modules and the connections between them are specified, which are the constituents of the blocks of Fig. 1, also specifying the type of ligature that exists between the terminal blocks and the external components. In Figs. 2a and 2b have some common characteristics. There is a structurebase (28) that supports the modules and connections and on which the box (13) is coupled with disposable tips. It can be seen that there is no coupling base (C), or that at most this is the same box (13). In addition, we can see the set of disposable tips (14), and the selected disposable tip (15) to be inserted at the end of the nozzle (11). The box (13) and the disposable tip (15) are located at an angle a, and there are also the couplings (16), one of which enters on the base structure (28) directly and another on a bridge (44) which also sits on the base structure (28). The nozzle (11) is at an angle ß to the main direction Dp, and the central block (20) internally has an intermediate block of common components (40) or (42), for each of Figs. 2a and 2b respectively, from which the various connections to the modules and action components exit, corresponding to the terminal blocks of Fig. 1. The terminal ejection block (3) of Fig. 1 is the same for Figs. . 2a and 2b, and consists of an ejection module (38) that is located in an extreme or resting position and has a connection (50) to the block of common components (40) or (42) mentioned above, and can be move to the position (38A) by acting directly on the disposable tip (12) to separate it from the nozzle (11) (ligature (21) in Fig. 1). From the block of common components (40) or (42) first activates the ejection module (38) which, as indicated by the double-direction arrow, passes to position (38A), separates the disposable tip (12) from the nozzle (11) and returns to its initial position at (38), as indicated by the double arrow. This is not shown in Fig. 2b for a matter of clarity with the remaining specified modules, but themovement from (38) to (38A) is present in this case in the same manner as in Fig. 2a. There is also a selection module (43) for separating the disposable tip (15) from the assembly (14), and another pushing module (45) acting on the assembly (14) to move and guide it. Both modules are connected to each other, through the connection (56), and connected to the set of common components (40) or (42) by the connection (55).
Fig. 2a shows that the insertion block (10B) of Fig. 1 is formed in this case by an insertion module (41) that is fixed and acting directly (ligature (28) in Fig. 1) on the disposable tip (15), the module (41) being able to be coupled to the box (13) or seated on the base (28). In addition, the module (41) has a connection (52) with the block of common components (40). The position in which the nozzle (11) is initially is an extreme or resting position, but can be moved to the position (11A) at an angle a and aligned axially with the disposable tip (15). This movement is also activated from the block of common components (40). The movement module (39) acts by performing a combination of translation and rotation movements, transmitting these movements to the nozzle (11), and then positioning itself at (39A), with the nozzle at (11A). In this position, the insert module (41), which is trapped to the disposable tip (15), inserts this at the end of the nozzle (1 A). From this action, two processes are performed in parallel, both activated from the block of common components (40). One action is that the nozzle returns to its initial position completing the movement cycle (as indicated by the arrow withdouble direction) to remain at an angle ß, in the pipetting direction DB (see Fig. 1). The other action (in parallel to the previous one) is that of the set of disposable tips (14) one of them is again selected to be positioned in (15), which is also done from the block of common components (40) through the action of the push modules (45) and selection (43), which belong to the blocks (9) and (10B), shown in Fig. 1, respectively. The push module (45) moves and guides the assembly (14), so that the selection module (43) can push a disposable tip and separate it from the rest by positioning it in (15), and is trapped by the insertion module ( 41).
In the case of Fig. 2b the nozzle (11) is fixed and disconnected from the block of common components (42), which is inside the central block (20), and the insertion action is different from the previous case. As already mentioned, the ejection module (38) is the same and performs the same operation as in the case of Fig. 2a, having to exert the force necessary to overcome the friction between the disposable tip (12) and the nozzle ( 1 1) to separate them. Here the manner in which the disposable tip (15) becomes positioned in (12) is changed, since there is a mobile insertion module (46), which is in an intermediate position, and goes to the position (46A) to take the disposable tip (15) and then to the position (46B), that is to say bringing it towards the position (12) and inserting it in the mouthpiece (11). In parallel to the previous action, the action of positioning a new disposable tip in (15) from the set of disposable tips (14), through the push module (45) and the selection module (43), is also performed. such that the moduleof insert (46) arrives at position (46A) at just the right moment to catch the disposable tip (15).
The two previous examples show the aspects considered prior to the description of both figures. Especially it can be seen that several of the terminal blocks of Fig. 1 have been grouped into a single subsystem, which we call insertion / ejection subsystem, due to the existence of the common components modules (40) and (42), since where the activation of the modules corresponding to the terminal blocks of Fig. 1 is carried out., we must clarify that, since in the operation and in the control of this subsystem, components or modules of the terminal blocks (1), (2), (7) and (6) of Fig. 1 can also intervene, when such components or modules are already specified, as would be the case with a more general schematic diagram than that of Figs. 2a and 2b, and the complete insertion / ejection subsystem also includes components of such terminal blocks.
PIPETEO METHOD OR FORM OF USING THE PIPETEO SYSTEM. The general method for the case of the pipetting system of Fig. 1 is applicable to both manual devices and automated pipetting equipment. The steps followed in the general pipetting method, ie when the system is defined at level 1, are:a) the user operates on the coupling terminal block (8), and is responsible for coupling the two base structures (C) and (D), so that the box (13) is at an angle,b) the user programs the development of functions and operations to be performed through the terminal block of interaction with the user (1), or data can be entered or sent through the communication terminal block (2), c) in both previous cases the actions are recorded and the necessary data are taken inside the terminal block of control and data processing (6), d) the terminal block of location / section (9) together with the terminal block of insertion (10B) selects a disposable tip (15) of the assembly (14) that is inside the box (13),e) a disposable tip (12) is inserted in the end of the nozzle (11) activating the insert terminal block (10B) of disposable tip, also having one of the following options:• mobile nozzle: the nozzle movement terminal block (5B) positions it above the detachable disposable tip (15), which is inside the box (13), aligning both in the axial direction,· Fixed nozzle: the insertion terminal block (10B) with a disposable tip takes it to the position below the nozzle (11), aligning both in the axial direction,f) the pipetting system is ready for the first liquid pipetting operation, which is performed through the suction / dispensing terminal block (4),g) the disposable tip (12) already used is separated from the nozzle (11) and discarded, through the terminal ejection block (3).
The Pi pipetting method, which is established at level 2, can be seen in Fig. 3. In the corresponding pipetting system, the insertion / ejection subsystem is specified, and several modules and components are defined. The steps should be divided, as for the general case, for when using mobile nozzle or fixed nozzle. For the first case (mobile nozzle) the steps that follow are.(130): carry out preparation and conditioning, prior to the pipetting procedure: selection of the volume to be dispensed, choice of the appropriate disposable tip, preparation of containers, material and liquids to be transferred, as well as the coupling of the device or head of pipetting with the disposable tip container,(131): start of the process of inserting the disposable tip at the end of the nozzle (11) from the activation of the insertion / ejection subsystem, from the subsystem of interaction with the user or from the communication and interconnection subsystem.(132A): from the block of common components (40) and with the action of the movement module (39), which performs a combination of translation and / or rotation movements, the nozzle (11) moves to position (axially aligned ) over a disposable tip that is inside the box (13),(132B): a new disposable tip (15) is selected inside the box (13), by means of the selection module (43), acting in conjunction with the push module (45), which also guides the assembly (14) so that the insert module (41) can catch it and hold it in position,(133): when the mouthpiece and the disposable tip are facing, by means of the action of the insertion module (41), the disposable tip (15) is inserted in the mouthpiece (11A),(134): the nozzle (11), with the disposable tip inserted at its end, moves until it is positioned again at an angle ß, again with the intervention of the movement module (39A) to its initial position at (39), ending thus the insertion process of the disposable tip.(135): start of the liquid aspiration / dispensing process, by operating the suction / dispensing subsystem. Vacuuming liquid from a container into the disposable tip (12).(136): dispensing of liquid from the disposable tip to another container, and completion of the aspiration / dispensing process.(137): start of the process of ejection and replacement of disposable tips through the ejection module (38), which has a movement activated from the block of common components (40), which allows the separation of disposable tip (12) from the nozzle (11),(138): Question: Are disposable tips in the container and more tests are required ?. The possible answers are: YES or NO. YES: the process starts again from step (131). NO: End of the pipetting process and continue with the next step.
E4: End of the Pi pipetting method.
In the case of a fixed nozzle, the following steps are modified:(132A): from the block of common components activation of the insertion / ejection subsystem is performed, which allows the insertion module (46) to take the disposable tip away (15), taking it in position (46A), to position it as the disposable tip (12), inserted in the end of the mouthpiece (11).(133): when the mouthpiece and the disposable tip are facing, by means of the insertion module in (46B), the disposable tip is inserted in the mouthpiece (11),(134): the insertion module is positioned in (46) to allow the completion of the aspiration / dispensing process.
EXAMPLES WITH DEVICE DIAGRAM.
EXAMPLE 1. Manual pipetting system with vertical movement of the nozzle, with a handle, with an insert / ejection subsystem and a box with disposable tips attached.
Fig. 4a shows a schematic representation of a manual pipetting system, which has been cut at the average height of the three-dimensional structure along the axial direction DA. This corresponds to the main direction DP of the pipetting system of Fig. 1, and reference point R must be taken as reference. In this case the pipetting system has a housing (71) with an upper extension (75) per above and to one side of the buttons (73) and (74), which allows the displacement of the nozzle (78) in the axial direction thereof. It also has a handle (72), a button (73) ofdrive for aspiration / dispensing, a push button (74) for insertion / ejection of disposable tip, and a display (86) where the volumes of aspiration and dispensing of liquid can be seen. There is a box (76) which is located at an angle a = 0 and is held by the flexible locks (80), whereby the nozzle (78) moves downward and upward to be able to insert a new disposable tip, as (79), and for the aspiration / dispensing operation. On the housing (71) most of the components seat, with a suction / dispensing module (85) and an insertion / ejection module (88). The suction / dispensing module (85) is activated from the button (73) by the connection (69), and then connected to the pressure chamber (84), and this is connected in turn, by means of a flexible hose ( 83), with the mouthpiece (78). The insertion / ejection module (88) is activated from the button (74) through the connection (96), and is extended by a rod (91), which has a return spring (89), and can push a pair of heads, such as (92), which are located on both sides of the plane through which the disposable tips (from right to left of the page) that are inside the box (76) are displaced. These heads have (each) a drive spring, such as (93) and rest on a base, such as (94). The nozzle (78) has a rack (95) that engages the gear (87), which is controlled by the impeller (90) (mechanical or electronic), connected in turn to the insertion / ejection module (88) by connecting (97).
We highlight in this case the following subsystems:• the insertion / ejection subsystem consists of the button (74), the connection (96), the insertion / ejection module (88), the connection (97) to the impeller (90), which act on the gear (87) connected to the rack (95) of the nozzle (78), the stem (91) with the spring (89), the pair of heads (92) to one side and to both sides of the nozzle (77), the pair of springs with shank (93) and base (94), a push subsystem for the disposable tips inside the box (76),• the interaction subsystem with the user consists of the activation buttons (73) and (74), the display (86) to display the volumes of aspiration / dispensing, the connections (69) and (96), the module aspirated / dispensed (85) and the insertion / ejection module (88).
When the user operates the button (74), the insertion / ejection module (88) causes the ejector (77) to come down first, ending in the form of a tube surrounding the nozzle (78), which pushes and separates the disposable tip (79) of the nozzle (78). Once this happens, and the ejector (77) reaches a certain position where ejection is ensured, the insertion / ejection module activates the impeller (90) that moves the gear (87), causing the nozzle (78) rise to a position above the box (76), as seen in Fig. 4b. The position of the ejector (77) is restored with the spring (82) which is on the base (81). While the user continues to operate the button (74) a little lower, the rod (91) moves the pair of heads (92) also downwards, compressing the corresponding springs (93) and allowing a disposable tip to be locatedbelow the nozzle (78), trapped by the pair of heads (92) and separated from the rest (see Fig. 4b). In such conditions, when the user releases the button (74) the nozzle (78) lowers a little and the pair of heads (92) are also free and, driven by the pair of springs (93), insert the disposable tip over the end of the nozzle (78). When the pair of heads return to their initial position, the nozzle (78) moves downward with the disposable tip (79) at its end. Both pass inside the tube of the ejector (77), since it has components inside that allow the passage of the disposable tip (79) down but not up. The disposable tips on the inside of the box (76) are then ready to locate a new disposable tip in position when the nozzle (78) goes back up. The set of components for performing this operation can have a wall with springs inside the box (76), in a similar way to the magazine of a rifle or by a band rotating with pulleys, which drag the disposable tips. Already in the final position, with the disposable tip (79) at the end of the nozzle (78) the system is again ready for the aspiration / dispensing operation (as in Fig. 4a).
EXAMPLE 2. Manual pipetting system with fixed nozzle, with movement of insert / ejection subsystem components, a handle and a box with disposable tips attached.
This case is shown in Fig. 5a, where we see a schematic representation with a cut at the average height of the three-dimensional device, when viewed from R, and with the axial direction DA as in the previous example. It canto see that it consists of a casing (100), a lower cavity (114), with a curved wall, through which the insertion rod (115) and a handle (72) move (rotationally). There are also a couple of buttons (73) and (74) that activate the central modules of the suction / dispensing (85) and insertion / ejection (101) sub-systems, through the connections (69) and (102) respectively. The suction / dispensing subsystem is extended with the chamber (113) and a connection tube (119) that connects to the nozzle (118), which is inside the ejector (117). This ejector is moved from the interface (103) which is next to the central insertion / ejection module (101). The interface (103) makes the head move (105), which also has a spring (104) that restores it to its initial position. In the extension of the right, corresponding to the sector with dotted line, the detail of the components is seen. Said head (105) has a flange (1 0), and a lock (107) located internally on a cylindrical hole of the head (105) which, by means of a transverse axis, moves on the guide (), and also has a spring (106) that sits on the wall of the hollow in the head, which restores the lock (107) to its initial position. The initial position of the head (105) and of the lock (107) is that shown in Fig. 5a. From the head (105) comes a side arm (109) that ends with the ejector (117). In the same figure the box (76) with disposable tips inside it is also observed, at an angle a = 90 degrees, which is coupled on the handle (72) by means of the flexible locks (80). The insertion stem (115) has a return spring (116) and canrotate around the axis (121) located in the base (120). This rotation is activated by the switch or knob (112) that is part of the drive module (108). The insertion rod (15) terminates as a clamping head (124), for the disposable tip that remains inside it, and enters the cavity (123), on the base of the handle (72), and its position is detected by the sensor (122), which is connected to the insertion / ejection module (101). This disposable tip will be moved from the inside of the box (76) to the end of the nozzle (118), being located in position (79).
We highlight here the following subsystems:· The suction / dispensing subsystem is extended with the chamber (113) and a connection tube (119) that connects to the nozzle (118), which is inside the ejector (117),• the insertion / ejection subsystem is prolonged with an interface (103), a head (105), with a spring (104) that returns it to its initial position, and has a flange (110) and a latch (107), located inside a cylindrical hollow of the head (105) and having a spring (106), a guide (111), on which the head (105) moves, a lateral arm (109), which leaves from the head ( 05) and ends with the ejector (117), an insertion stem (115), which has a return spring (116) and can rotate about the axis (121) located in the base (120), ends like a head of holding (124), for the disposable tip that remains inside, and enters the cavity (123), on the base of the handle (72),Pressing the button (74) downwards with a force F, as shown in Fig. 5b, activates the insertion / ejection subsystem and the head (105) moves downwardly stretching the spring (104). Firstly, the result is to separate the disposable tip (79) from the nozzle (118), being pushed by the ejector (117), since this is directly connected to the arm (109) seated in the head (105) . Upon reaching the end of the path down, the head (105) operates, through the switch (112), the driver module (108), which can have a motor. The driving module (108) is responsible for moving the shaft (121) and causing the clamping head (124), which has one of the disposable tips that are in the box (76), to have a rotation of 90 degrees (in the direction of the arrow) to get upright. The latter can be seen in Fig. 5c, where the clamping head (124) has a cut, and is already positioned below the nozzle (118), with its upper end engaged in the head (105) through the tab (110) and the lock (107). This lock is protruding from the transversal hole that the head (105) has and the return spring (106) is compressed, forced by the movement on the guide (111). On the enlarged part on the right, the arrows indicate the directions of movement that the components driven by the springs (104) and (106) will have, while the spring (116), which is on the rod (115), is stretching. Upon releasing the button (74) the spring (104) exerts the greatest force of the insertion / ejection subsystem and also pulls the clamping head (124), then stretching the spring (116). The head (105) returns to its initial position and the lock (107), by the force exerted by the spring(106), follow the guide (111) to its position in Fig. 5a and release the end of the rod (115). In the position shown in Fig. 5d the effect obtained is that the disposable tip, contained in the clamping head (124), is inserted in the nozzle (118) due to the vertical force that the spring (104) develops . The upper end of the rod (115) has been released and the spring (116) will cause it to move downward, and finally the driver module (108) will cause the clamping head (124) and the rod (115) to perform the movement of rotation, around the axis (121), to position again in the manner indicated in Fig. 5a. The enlarged sector shows that when the lock (107) reaches the upper position on the guide (111), the spring (106) locates it towards its rest position and the head (105) is free, allowing the movement of the stem ( 115) in the direction indicated by the arrow, in the enlarged sector to the right of Fig. 5d, by the action of the spring (116). In this way, the pipetting system is ready for the aspiration / dispensing operation. Once this operation has been completed, the process is repeated again if necessary to insert a new disposable tip such as (79) into the end of the nozzle (118).
MODALITIES AND VARIANTS OF THE INVENTIONAs a matter of simplicity in the presentation of Fig. 1, it was previously established that each terminal block is associated with a single subsystem, however it can also occur in a different way. That is, depending on the architecture of the pipetting system, a terminal block may be associated with more than one subsystem or a subsystem may have several of the terminal blocks shown in Fig. 1. At the three different levels of definition it may happen that some elements corresponding to the diagram of that level are shared, either through intermediate blocks, components or modules. But in level 3, when there is a greater specification of the components, some of these, corresponding to a terminal block of level 1, may be shared in different subsystems as well. In short, the number of combinations and possible subsystems is also very varied. Fig. 1 clearly specifies the terminal blocks that act on the external components, interacting with the outside and inside of each other so that the pipetting system can perform its functions. But it can also happen that two subsystems act coordinated and therefore can be grouped as a subsystem more representative and more complete for the function or functions they develop. Examples of this were seen in Figs. 2a and 2b for mobile and fixed nozzle.
We should mention that, although Fig. 1 represents a single nozzle that takes a disposable tip each time, the system can be extended to the case ofNxM nozzles with N = 1, 2, M = 1, 2, taking the same number of disposable tips with the distances between nozzles that can be variable. Then, we should consider the following derived questions:• the box (13) now has the disposable tips arranged in an array of N x M x K, where K = 1, 2, ... the number of times that the pipetting system can be used with this box or the number maximum number of tests to be performed,• A total of N x M disposable tips are inserted and ejected at each pipetting operation, all at once, on and from the N x M nozzles.
These facts are also reflected in the different modalities and variants that we will see below.
Some variants and modalities arising from Fig. 1 are shown in Figs. 6a and 6b. In Fig. 1 is considered the block (5B) located within the base structure (D) and the terminal blocks of box coupling (8), location / section of disposable tips (9), and disposable tip insertion (10B) placed between the pipetting base (D) and the coupling base (C), that is to say that there is a part of the terminal blocks within it. However, there are other extreme possibilities, as well as several possible combinations between them, for the location of said blocks. In Fig. 6a the possibility is shown that the aforementioned blocks are all included within the coupling base (C), also considering that some intermediate block, which is inside the central block (20) in Fig. 1, also It may be partially within this structure. This implies a modification in the form of the device, in theTerminal blocks and connections that are in both structural bases (D) and (C). The other possibility is that shown in Fig. 6b, with the same blocks previously considered within the structure (D), so that the structure (C) is only a base for the box (13) or is directly the box (13). Between both cases, different combinations can be located with some blocks within the structure (C), others within the structure (D) and others shared between both structures.
The following modality shown in Figs. 7 refers to the possibility that the disposable tip (12), when ejected, is not thrown into an external container. An enlargement of the right part of Fig. 7 is shown in Fig. 7a., with a cut at height AA 'to be able to visualize the terminal blocks and ligatures in more detail. For this, the box (13) is now divided into two parts. One part is the box section (13A) with unused disposable tips, where the set (14) and the selected tip (15) are, such as the description given in Fig. 1. The other part is the box section Disposal / recycling (13B), which stores the disposable tips already used, for disposal or to enable the completion of a recycling process of the plastic involved in the disposable tips and in the double box (13A) / (13B). Now we have a new subsystem.
· Discard / recycling subsystem, on the terminal block (3A): For this, there is a block (3A) in replacement of the ejection block (3) of Fig. 1, which is responsible for separating the disposable tip (12 ) of the nozzle (11). It has the ligature (21A) for the case of pipetting systems with fixed nozzle, and when theDoor P9 is closed. From there it is carried by the terminal block (10B) to the box section (13B). For the case of mobile nozzle (P9 open) is responsible for locating the disposable tip discarded inside the box section (13B) and separate it there from the nozzle (11). In both cases we must also observe that there is a new angle? which defines the direction DG for discarding the disposable tip already used within the box section (13B). The terminal control block (6) also has a sensor for detecting the positioning of the nozzle and / or disposable tip with respect to the box section (13B). This process represents something new and very suitable for the handling of consumables within the laboratory, being simpler and direct (for the user) the handling of such materials. We do not find it today, and it is applicable to automated equipment and manual devices.
• Disposable tip location / insert subsystem, on the terminal block (9A): When the box is divided into two sections, the section (13A) containing disposable tips that have not yet been used, and the section (13B) initially empty and where the disposable tips already used will be placed, then the terminal block (9) retains the functions and ligatures on the box section (13A). But now there is a new terminal block for placing / inserting disposable tips (9A), with ligatures (33A) and (33B), which perform the function of positioning and guiding the set of disposable tips (14A) within the box section (13B) The inserted disposable tip (15A), inside the box section (13B), is inserted into it with thecontribution of the discarding / recycling terminal blocks (3A), by means of the ligature (21 B), and of location / introduction of disposable tips (9A), by means of the ligature (33B). In addition, the introduced disposable tip (15A), inside the box section (13B), becomes part of the assembly (14A) through the joint action of the ligatures (33A) and (33B) of the terminal block of location / introduction (9A), and also has the ligature (23A) with the sensor (17B), on the box section (13A). The terminal block for control and data processing has the ligature (23B) with the sensor (17C), to determine the position of the inserted disposable tip (15A) in the box section (13B). In short, the terminal block (9A) is similar and has almost the same components as the terminal block (9), and can share several components between them, except that instead of fitting into the nozzle or taking the disposable tip ( 15), remove from the nozzle or deposit the disposable tip (15A), which is the disposable tip (12) when positioned over the box section (13B). This subsystem is not present in any type of device or pipetting system.
Figs. 8a and 8b are the two variants with double box, equivalent to the cases shown in Figs. 2a and 2b, where the modules of location / section (153) and location / discard (152) of disposable tips for boxes (13A) and (13B) respectively are shown. Both modules also guide the set of disposable tips within the box sections (3A) and (13B). The location / section module (153) has, in both Figs. 8a and 8b, a connection (166) to the block of shared components (157) and (158). In each of Figs. 8a and 8b, the location / discard module (152) has connectionsdifferent, (165) and (175) towards these blocks (157) and (158) respectively, since as the system is different (movable or fixed nozzle) the way in which it is introduced in the box section is different (13B ). In both cases, there is a different base structure (128) compared to Figs. 2a and 2b, since it requires a different distribution in the components and to cover the movement of the nozzle (11) or of the disposable tip (15), due to the double box. There is also a bridge (144) with greater extension or more robust, the couplings (151) located on the two sections of box (13A) and (13B), but no longer the disposable tip ejection module. We must also consider that now we have three positions in relation to the angles, ß and.. For the case of Fig. 8a the nozzle (11) moves to two positions (11 A) and (11 B) to face the two box sections (13B) first and then (13A), following the path of the arrows, but with a movement module (139), with positions (139A) and (139B) leading to the nozzle (11) to perform more travel than in the case of Fig. 2a. The modules are connected to the block of shared components (157) and (158), for Figs. 8a and 8b respectively, within the central block (20), with connections (163), (164) and (165) for Fig. 8a and (173), (174) and (175) for Fig. 8b, toward the corresponding modules that have functions similar to the cases of Figs. 2a and 2b. In Fig. 8a there is the insertion module (150), with a connection (170) to the location / section module (153), and in Fig. 8b it is called the insertion / disposal module (154). The latter takes four definite positions: in (154), (154A), (154B), (154C), moving in theaddresses indicated by the arrows, and is in replacement of the insertion module (46) having three defined positions: (46), (46A) and (46B).
From the variants presented in Figs. 7 and 7a, and the special cases of Figs. 8a and 8b also arise modalities for the method established in Fig. 3. The method described in the previous section (Fig. 3) also has its variants for the case of having a double box. In steps (131), (132A) and (132B) an insert / discard subsystem is activated, with the box having two sections: one with unused disposable tips (13A) and another with the disposable tips that have already been used (13B)For the case of mobile nozzle is modified:(137): Begin the process of discarding / recycling and replacing disposable tips, since the nozzle (11) with the disposable tip inserted at its end is positioned at (11 A), so that the location / discard module ( 152) separates the disposable tip from the nozzle and introduces it into the box section (13B), then positioning it as part of the assembly (14A).
For the case of a fixed nozzle, the following is modified:(137): Start of the process of discarding / recycling and replacement of disposable tips, since the insertion / disposal module (154) traps and separates the disposable tip (12) in the position (154B), to then take it to the position (154B) where the location / discard module (152) separates the disposable tip from the nozzle and introduces it into the box section (13B), then positioning it as part of the assembly (14A).
As is to be expected, the modification in the steps to be followed is also given in the case of the method at level 1 (Fig. 1), as described in the previous section, and in step g) where the disposable tip is separated ( 12) already used of the nozzle (11), it is also necessary to consider the cases of movable and fixed nozzle, for the double box of Fig. 7.