Fraction collector and method for operating same - Patents.com

Abstract

The present invention includes a support system (1, 2), a carrier (42) movably supported by the support system (1, 2), an extension arm (3) connected to the carrier (42), and at least one dispensing head (31) movably connected to the extension arm (3) for dispensing droplets, wherein the dispensing head (31) and the carrier (42) are configured to move relative to the support system in a first plane, a tray area (11) is designed to support at least one rack (6, 7), and the at least one rack (6, 7) is designed to hold at least one collection container (12, 14), and movement of the carrier (42) is achieved by a linear bearing Y-slide unit (41), the linear bearing Y-slide unit (41) is arranged below a linear bearing Y-rail (40), and the carrier (42) is attached to the linear bearing Y-slide unit (41).

Description

[Technical Field]

[0001] The present invention relates generally to the field of column chromatography, and in particular to a fraction collector and a method for operating a fraction collector, a cooling means configured for use in such a fraction collector, a rack configured for use in a fraction collector, and a dispensing head configured for use in a fraction collector. [Background technology]

[0002] Chromatography is a chemical process for identifying and quantifying components retained in a sample of solution. In this process, components in a solution are separated from each other as the solution moves through a stationary material held in a column. One or several chromatography pumps can pump the solution through the stationary material in the column under pressure. Fractions of the components can be collected into a series of individual containers by a fraction collector device. In some cases, the collected fractions in the individual containers / fraction tubes / collection vessels are transported by the fraction collector device and dispensed for further analysis.

[0003] Fraction collector devices are known that are used to receive fluid from a fractionation column and separate fractions of the fluid into containers. A nozzle for dispensing the fractions into the receptacles can be disposed on an arm that can be movable in two dimensions. An electric motor can move the nozzle in first and second directions, which can be orthogonal to each other.

[0004] Known fraction collector devices, however, can be relatively complex and expensive, and they have dimensions that require a significant space (footprint).

[0005] US Pat. No. 8,114,281 discloses a known fraction collector device that suffers from at least the problems of being complex and requiring a significant amount of space. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] U.S. Patent No. 8,114,281 Summary of the Invention [Problem to be solved by the invention]

[0007] The present invention aims to avoid the above-mentioned problems. The main object of the present invention is to provide an improved fraction collector which is simple, inexpensive and requires less space than fraction collectors known in the art. [Means for solving the problem]

[0008] According to the present invention at least the main object is met by an apparatus having the features defined in the independent claims.

[0009] Preferred embodiments of the invention are further defined in the dependent claims.

[0010] According to a first aspect of the present invention, there is provided a fraction collector device comprising a support system, a carrier movably supported by the support system, an extension arm connected to the carrier, and at least one dispensing head configured to dispense droplets and movably connected to the extension arm, wherein the dispensing head and the carrier are configured to move relative to the support system in a first plane, a tray area designed to support at least one rack, the at least one rack designed to include at least one collection container, and movement of the carrier is achieved by a linear bearing Y-slide unit, the linear bearing Y-slide unit being arranged below a linear bearing Y-rail and the carrier being attached to the linear bearing Y-slide unit.

[0011] An advantage of this is that the fraction collector is more compact than prior art fraction collectors. Another advantage of this embodiment is that it is less complex than prior art fraction collectors and therefore more reliable and / or easier to sterilize / clean etc.

[0012] In various example embodiments of the present invention, the linear bearing Y-rail is positioned at a position in the Z direction that is lower than the top surface of the at least one rack positioned above the tray area. For example, the Z direction can be parallel to an axis that is substantially perpendicular to the floor or support surface on which the fraction collector is supported in use. A lower position would therefore be considered closer to the floor or support surface than a position further away along this axis. The X and Y directions can therefore generally follow orthogonal axes in a plane (e.g., the first plane) that is generally parallel to the floor or support surface.

[0013] An advantage of these embodiments is that the fraction collector can be made very compact.

[0014] In various example embodiments of the present invention, the rack may include a cooling means including an enclosed cooling volume containing a cooling medium, the cooling means configured to at least partially surround at least one collection container.

[0015] An advantage of these embodiments is that there is no need to operate the fraction collector in a climate-controlled environment, which would enhance the usefulness of the fraction collector. The operator then simply places the cooling means in a freezer prior to use and uses the cooled cooling means when fractionation begins. The fraction collector can be operated at normal room temperature without risking the fractionated liquid in the collection vessels being destroyed.

[0016] In various example embodiments according to this invention, the dispensing head includes a transmitter and a receiver for detecting droplets, with a communication path between the transmitter and receiver intersecting the path of the droplets.

[0017] An advantage of these embodiments is that the movement of the dispensing head can be performed when it is known that droplets will not be ejected from the dispensing head, thereby minimizing droplet scattering.

[0018] In various example embodiments of the present invention, an aperture is provided in front of the receiver.

[0019] An advantage of these embodiments is that the accuracy of detecting droplet events can be increased.

[0020] In various example embodiments of the present invention, the transmitter is a source of electromagnetic radiation and the receiver is an electromagnetic radiation sensitive sensor.

[0021] An advantage of these embodiments is that different types of electromagnetic radiation sources and corresponding detectors can be used, for example, ordinary white light sources and sensors for detecting white light.

[0022] In various example embodiments of the present invention, the dispensing head further includes a tube that is wider than the droplet and made of a material that is transparent to electromagnetic radiation, and through which the droplet from the dispensing head is dispensed.

[0023] An advantage of these embodiments is that splashing of the dispensing head onto the electronics can be eliminated or at least reduced.

[0024] In various example embodiments of the present invention, the communication path between the transmitter and receiver is transmitted through the tube.

[0025] An advantage of this embodiment is that the detection electronics can be located in a splash-free area.

[0026] In various example embodiments of the present invention, the tray area is configured to support at least two racks of collection bins.

[0027] An advantage of these embodiments is that sequential fractionation can be performed by replacing a first rack with filled collection containers with a rack with empty collection containers while filling the collection containers in a second rack.

[0028] In various example embodiments of the present invention, the collection container is angled relative to a normal to the first plane.

[0029] An advantage of these embodiments is that droplet splatter can be further reduced. Instead of droplets falling onto the surface of the liquid within the collection container, where they may splatter outside the collection container, the droplets will instead be directed toward the interior wall of the collection container with an inclined collection container. Any splatter of droplets from impacting the interior wall will be in a direction toward other interior wall areas of the collection container, thereby keeping the liquid inside the container. Droplets impacting an inclined surface will themselves further reduce splatter compared to impacting a plane perpendicular to the droplet's path.

[0030] In various example embodiments of the present invention, the movably supported carrier and / or the movably connected dispensing head are provided with a splash cover configured to inhibit liquid splashes exiting the at least one collection container from entering the linear movement mechanism of the carrier and / or dispensing head.

[0031] An advantage of these embodiments is that splash contamination of the linear motion mechanism is eliminated or at least reduced to a minimum. Another advantage is that the cover reduces damage to any electrical components hidden inside the cover.

[0032] In various example embodiments of the present invention, the electronics within the dispensing head are provided in a waterproof housing.

[0033] An advantage of these embodiments is that liquid damage to electronic devices is virtually eliminated.

[0034] In various example embodiments of the present invention, the dispensing head is assembled with a snap fit.

[0035] An advantage of these embodiments is that manufacturing of the dispensing head can be kept to a minimum. Another advantage is that assembly and disassembly of the dispensing head can be performed without any tools. Yet another advantage is that servicing the dispensing head is easier than prior art dispensers.

[0036] In another aspect of the present invention, there is provided a method for operating a fraction collector, said method comprising: a. providing a carrier movably supported by a support system; b. providing an extension arm connected to a carrier, wherein at least one dispensing head for dispensing droplets is movably connected to the extension arm, the dispensing head and the carrier configured to move relative to a support system in a first plane; c. providing a detection device configured to detect said droplets from said dispensing head; d. moving the dispensing head in synchronization with the droplets so that the droplets from the dispensing head fall into at least one collection container provided on the tray area, wherein the movement of the carrier is achieved by a linear bearing Y-slide unit, the linear bearing Y-slide unit is disposed under the linear bearing Y-rail, and the carrier is attached to the linear bearing Y-slide unit; Includes:

[0037] The advantage of this method is that it is less complicated than prior art methods of operating fraction collectors.

[0038] In another aspect of the invention, there is provided a cooling means configured for use in a fraction collector, said cooling means comprising an enclosed cooling volume containing a cooling medium, said cooling volume configured to at least partially surround at least one collection vessel.

[0039] One advantage of such a cooling means is that it can eliminate the need to use a fraction collector in a temperature-controlled environment. Such a cooling means can be designed to be used in conjunction with one or more existing microtiter plates, or can be designed as a cooled microtiter plate, i.e., having both wells for collection vessels and a cooled volume inside the microtiter plate that at least partially surrounds the wells for receiving the collection vessels.

[0040] In another aspect of the present invention, there is provided a rack configured to contain at least one collection vessel for use in a fraction collector, said rack comprising cooling means including an enclosed cooling volume containing a cooling medium, said cooling volume configured to at least partially surround said at least one collection vessel.

[0041] An advantage of these embodiments is that the rack may have integrated or removable cooling means which will increase the utility of the fraction collector.

[0042] In yet another aspect of the present invention, there is provided a dispensing head configured for use in a fraction collector device, said dispensing head including a nozzle for delivering droplets of liquid, said droplets being dispensed through a tube, the tube being wider than the droplets and made of a material that is transparent to electromagnetic radiation.

[0043] An advantage of these embodiments is that the electronics within the dispense head can be located in a splash-free area.

[0044] Further advantages and features of the present invention will become apparent from the following detailed description of the preferred embodiments.

[0045] A more complete understanding of the above and other features and advantages of the present invention will become apparent from the following detailed description of the preferred embodiments taken in conjunction with the accompanying drawings. [Brief explanation of the drawings]

[0046] [Figure 1] FIG. 1 is a schematic front perspective view of one example embodiment of a fraction collector according to the present invention. [Figure 2] FIG. 2 is a schematic rear perspective view of the same example embodiment of a fraction collector as shown in FIG. 1. [Figure 3] FIG. 3 is a schematic partial cross-sectional side view of the same example embodiment of the fraction collector as shown in FIG. 2, without the covers on the arms. [Figure 4]FIG. 1 is a perspective view of an example embodiment of a tube rack. [Figure 5] FIG. 1 is a side view of a tilted collection bin. [Figure 6] FIG. 1 is a front perspective view of an example embodiment of a dispensing head according to the present invention. [Figure 7] FIG. 7 is a cross-sectional side view of the dispensing head in FIG. 6. [Figure 8] 1 is a close-up portion of one example embodiment of a drop sensor mechanism in a dispense head according to the present invention. [Figure 9] FIG. 1 is a front perspective view of an example embodiment of a fraction collector with cooling means according to the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0047] In the following description, container, fraction tube, microtiter tube or collection vessel are different names for the same thing, i.e. a means for collecting a predetermined amount of liquid. Said container, fraction tube, microtiter tube or collection vessel can be a cylindrically shaped tube with parallel walls or a conically shaped tube with non-parallel walls.

[0048] FIG. 1 shows a schematic front perspective view of an example embodiment of a fraction collector 100 according to the present invention. The fraction collector 100 includes a support system, an arm 3, and a tube rack 4. The support system can include a bottom frame 1 and a mainboard housing 2. The bottom frame 1 can include a tray area 11 designed to support at least one rack 6, 7 of collection vessels 12, 14. The design intent is to build an open-architecture, robust, low-cost fraction collector 100 that can help prevent flammable liquids from accumulating in dangerous concentrations. In various example embodiments, the support system can be a single unit, two units as disclosed herein, or three or more units.

[0049] Fraction collector 100 is designed to fit in a tunnel below or on a bench next to a column chromatography system, which may be, for example, any one of an adsorption chromatography system, an ion exchange chromatography system, an affinity chromatography system, or a gel permeation chromatography system.

[0050] The fraction collector 100 can have a support system made of cast aluminum or any other suitable rigid material or combination of materials. The fraction collector 100 can also include at least one cover plate, which can be injection molded, 3D printed, etc.

[0051] The fraction collector 100 can have a capacity of two racks or microtiter plates 6, 7. The racks 6, 7 can contain 24 / 48 / 96 or any other suitable number of wells, one each configured to receive a collection vessel 12, 14.

[0052] Collection containers 12, 14 of different volumes may require racks 6, 7 of different heights. Using a low rack or microtiter plate 6 may require the distance plate 5 to maintain the same level from the arm 3 to the microtiter plate surface, i.e., the same height from the opening of the collection container 12, 14 to the origin of the droplet filling it, regardless of the dimensions of the rack 6, 7 itself. In various example embodiments, the collection containers 12, 14 can be Eppendorf tubes. In various example embodiments, the racks 6, 7 can have at least one integrated collection container 12, 14. In various example embodiments, the racks 6, 7 can have at least one integrated collection container 12, 14 and at least one removably attached collection container 12, 14. In various example embodiments, the racks 6, 7 can include only removably attached collection containers. The removably attached collection containers can be of the same volume or at least two different volumes.

[0053] The fraction collector 100 can support X and Y motions for scanning a predetermined area with the dispensing head 31 in a serpentine, linear, or circular fashion. A serpentine fashion can have a long stroke in the X axis and a short stroke in the Y axis, or a short stroke in the X axis and a long stroke in the Y axis. In a machine such as that shown in FIG. 1 , the X axis is considered to be the movement of the dispensing head 31 along the arm 3, and the Y movement is the movement of the arm 3 itself. In a linear fashion, the collection vessels 12, 14 are always filled starting from one side of the racks 6, 7 and ending on the opposite side of the same racks 6, 7; the starting position can be from either the X or Y axis; i.e., the long stroke for filling is in the Y or X direction, respectively, and then the collection vessels 12, 14 can return to fill any one of the other rows. The difference between the linear X and Y movement of the dispensing head 31 and the serpentine X and Y movement of the dispensing head 31 is that the serpentine fashion fills the collection vessels 12, 14 even on the long return stroke, unlike the linear movement. The circular X and Y movement can begin at any position along the outermost X or Y row of the rack or microtiter plate 6, 7. Collection vessels 12, 14 are filled along the outermost X and Y row, then continue along the next outermost X and Y row until the central collection vessel position is reached. Alternatively, the circular movement can work from the central collection vessel position toward the outermost X and Y row of the rack 6, 7.

[0054] Providing at least two racks or microtiter plates 6, 7 on the tray area 11 supports removal of a first, non-working rack or microtiter plate 6 while dispensing on a second rack or microtiter plate 7.

[0055] A tube rack 4 can be removably attached to at least one side of the bottom frame 1. In FIG. 1, the tube rack 4 is attached to the left side of the bottom frame 1 and has five tubes 8, 9 along the X-axis of the machine, i.e., along the stroke of the dispensing head 31. A home position can be above the home tube 9. The home tube can be a 15 ml tube positioned to collect any droplets that can be dispensed by the dispensing head 31 when it is positioned in the home position. Liquid flow-through that does not need to be fractionated can be collected in any one of four flow-through tubes 8. The flow-through tubes 8 can be 50 ml tubes. The flow-through tubes 8 can be filled during linear or serpentine movement of the dispensing head 31.

[0056] 4 shows a perspective view of one embodiment of tube rack 4. Tube rack 4 can be snap-fit ​​into bottom frame 1. In an alternative embodiment, at least two tube racks can be used, either on both sides of tray area 11 or on alternate sides of tray area 11, i.e., along the X and Y axes. In one embodiment, tube rack 4 is positioned between two collection receptacle locations 12 and 14 so that it can be reached without having to move over the other receptacles, thereby avoiding the risk of contamination.

[0057] The tube rack 4 may include two parts: a frame 4' and a top plate 4'' that includes four flow-through holes 8' for receiving flow-through tubes 8 and one home hole 9' for receiving home tube 9. The tube rack may be made of PBT or any other suitable material that is UL94-V0 classified.

[0058] The tube rack 4 can be attached to the bottom frame 1 using two guide hooks and a snap fit with a release button. The tube rack 4 can be dishwasher safe. The frame can have drainage holes to prevent dishwasher water from collecting.

[0059] Fractionation can be performed in one of the collection vessels 12, 14. The first microtiter plate or rack 6 can be removed while fractionation is being performed in any one of the vessels 14 in the second microtiter plate or rack 7.

[0060] The bottom frame 1 can be a die-cast aluminum piece with some machined features. All or most of the components of the fraction collector 100 can be assembled to the bottom frame 1, and therefore it is important that the bottom frame 1 has high tolerances.

[0061] Alignment features for positioning the microtiter plates 6, 7 can be machined on the tray area 11 of the bottom frame 1. High tolerances on the alignment features can be important to allow for high accuracy positioning of the racks or microtiter plates 6, 7. The alignment features can be machined to fit corresponding alignment features in the microtiter plates 6, 7 according to their standard dimensions. There can be markings on the tray area 11 corresponding to different types of microtiter plates, which can increase the usability of the fraction collector 100.

[0062] 1, only the connection portion 30 of the dispensing head 31 is shown, the rest of the dispensing head is hidden by a cover 3' of the arm 3. A flexible tube or capillary 20 can be arranged to attach the dispensing head 31 in the fraction collector 100 to an external column chromatography system.

[0063] 6-8 show various views of the dispensing head 31. The dispensing head 31 comprises a housing 33, a cover 32, a connection part 30, and a support 34 for electronics and / or means for detecting droplets. A nozzle 72 is configured to deliver droplets 74 of liquid from a chromatography system attached to the dispensing head 31.

[0064] To resist splashing of the droplets 74 onto various parts of the dispensing head 31 or any other component of the fraction collector, the droplets 74 are allowed to fall into the transparent pipe 68 before leaving the dispensing head 31 through the outlet passage 35. The cover 32 functions both as splash protection for the electrical and mechanical components and as a protective shield to prevent damage to sensitive components inside the cover 32. The cover 32 can be assembled to the housing 33 with a snap fit. At least a part of the dispensing head 31 can also be removably attachable to the fraction collector device 100. Such a dispensing head 31 can therefore be removable for cleaning and / or replacement during service, as needed.

[0065] The dispensing head 31 may also include at least one flag fork sensor or other type of sensor capable of detecting a home position in the X and / or Y directions. The dispensing head 31 may also include a transmitter and receiver for detecting droplets falling from the dispensing head. Droplet detection may be performed by an electromagnetic radiation source 62 and an electromagnetic radiation detection sensor 66, which are positioned to detect when a droplet 74 is released from the nozzle 72 and passes the sensor, i.e., interrupts the electromagnetic radiation path 37 between the electromagnetic radiation source 62 and the electromagnetic radiation detection sensor 66. To improve the accuracy of the electromagnetic radiation detected from the electromagnetic radiation source 62, an aperture 64 may be positioned in close proximity to the sensor 66. In various example embodiments, multiple apertures 64 may be positioned on the movable plate in front of the sensor 66. Different apertures may be selected depending on the size of the nozzle, and therefore the size of the droplets; i.e., a smaller aperture may be selected for small droplets and a larger aperture may be selected for large droplets. The electromagnetic radiation source 62 may be any suitable light source, such as a white light source, a laser source, or an infrared source. The sensor 66 is selected with respect to the electromagnetic radiation source used. The electromagnetic radiation path 37 between the sensor 66 and the electromagnetic radiation source 62 can pass through the transparent pipe 68.

[0066] Both the support systems 1, 2 and the arm cover 3' have an open design to avoid the possibility of vapors from flammable liquids being captured by the fraction collector, as such captured vapors could present a safety hazard. The surfaces facing the customer / system user can have a smooth, easy-to-clean design. The open architecture also provides good visibility for customers to track / view fractions. The device is minimized in size to provide a small area and / or volume footprint, making it easy to handle. Various embodiments of the present invention can be provided with an area footprint with a width w≦320 mm and a depth d≦270 mm, optionally with a height h≦190 mm (e.g., h≦170 or 180 mm without various inserts / trays / racks inserted). For example, 150 mm≦w≦320 mm, 120 mm≦d≦270 mm, and h≦170 mm. Preferably, various embodiments also have a mass m of 4 kg or less. For example, 1 kg ≦ m ≦ 4 kg, 1 kg ≦ m < 4 kg, 1 kg ≦ m ≦ 3 kg, 2 kg ≦ m ≦ 4 kg, 2 kg ≦ m ≦ 3 kg, etc.

[0067] The arm 3 can include a carrier 42, a linear bearing X-rail 50, a dispensing head 31, motor electronics (not shown), and an arm cover 3'.

[0068] The dispensing head 31 includes a linear bearing X-slide unit at its bottom end. The dispensing head 31 runs on a linear bearing X-rail 50, which is connected to the motor electronics by a flex cable. The arm cover 3' can have a snap fit to the carrier 42. The arm cover 3' has an open design to avoid the possibility of vapors from flammable liquids being captured by the fraction collector, as such captured vapors could present a safety hazard. The arm cover 3' can have a feature to cover the motor electronics and function as a design feature. The movement of the arm 3 can have a zero position for calibration when the arm detects sensors X and Y. This movement can be X or Y only to keep current as low as possible, or X and Y to increase the speed of positioning. The linear bearing X-rail 50 is attached to the carrier 42.

[0069] The carrier 42 includes a linear bearing Y slide unit 41. The carrier 42 is attached to the underside of the linear bearing Y slide unit 41. The linear bearing Y slide unit 41 moves along the linear bearing Y rail 40. The underside of the linear bearing Y slide unit 41 is located below the linear bearing Y rail 40. By attaching the carrier 42 to the linear bearing Y slide unit 41, at least a portion of the carrier 42 is positioned below the linear bearing Y rail 40, i.e., at least a portion of the carrier 42 hangs below the linear bearing Y rail 40, which can be considered an inverted / reversed linear bearing motion. The Y-axis motion is achieved by placing the linear bearing Y slide unit 41 below the linear bearing Y rail 40. The carrier 42 is attached to the linear bearing Y slide unit 41 and is configured to support a linear bearing X rail 50 extending above the linear bearing Y rail 40. The pipe 68 and / or the splash cover 3', 32 can protect the carrier 42 and / or the linear movement mechanism of the dispensing head 31, i.e., the Y rail 40, the X rail 50, the linear bearing Y slide unit 41 and the linear bearing X slide unit, from liquid splashes.

[0070] The carrier 42 may be provided with pins 44 with bushings that run in grooves 45 in the bottom frame 1 to distribute the load from the arm 3 to the support system and reduce torque on the linear bearing Y-rail 40. This provides a smoother ride without vibrations in the arm 3. In an alternative embodiment, the pins are provided on the linear bearing Y-slide unit 41. The pin 44 and groove 45 components provide additional support in a direction perpendicular to the Y-axis motion and are designed to reduce torque loads on the Y-axis bearing components. The pin 44 and groove 45 components may be designed to reduce torque in the clockwise and / or counterclockwise directions relative to the Y-rail 40.

[0071] The linear bearing Y-rail 40 is mounted to a support system on either the bottom frame 1 or the mainboard housing 2. The mainboard housing 2 is shown in Figures 1-3 as including a mainboard base 2' with a mainboard cover 2'' thereon. The mainboard housing has an opening 77 configured to receive the carrier 42 and allow the carrier 42 to move freely between its end positions. The linear bearing Y-rail 40 can be mounted to the mainboard cover 2''. Drive means for X-axis and / or Y-axis movement can be threaded rods, rack and pinions, belt drives, or the like.

[0072] In various exemplary embodiments of the present invention, the linear bearing Y-rail 40 for the linear bearing movement of the carrier 42 can be located below the opening of the collection containers 12, 14. In various exemplary embodiments of the present invention, the linear bearing Y-rail 40 for the linear bearing movement of the carrier 42 can be located below the tray area 11. By providing the linear bearing Y-rail 40 at a low position within the fraction collector, a compact design can be achieved. The low position of the linear bearing Y-rail also allows the bottom frame 1 to be effectively used as a torque reducer for linear movement by distributing the load from the arm 3 to the support system and preventing torque on the linear bearing Y-rail 40 using the pin 44 with a bushing running within the groove 45 in the bottom frame 1. In an alternative embodiment, the groove 45 is located in a support structure 47 attached to the mainboard base 2'.

[0073] On the carrier 42 there may be two fork sensors that move along ridges with openings to detect the end position of the carrier.

[0074] The carrier 42 is the mechanical link between the X and Y linear bearings. This can affect the tolerance chain of the fraction collector 100, especially the perpendicularity between the X and Y travel of the linear bearings. The carrier 42 can be a die-cast aluminum part. Features can be machined that can affect the tolerance chain.

[0075] The cover 3' protects the electronics in the arm 3 from condensation droplets from the carrier 42 and as a mechanical protection to prevent accidental contact with this by the customer.

[0076] The linear slide units for X and Y movement can be modified Stork Drives® 1 / 4" pitch units. The linear bearing X rail 50 and linear bearing Y rail 40 can have the same pitch but different lengths.

[0077] The fraction collector can further be configured to accept a cooled collection vessel to keep the fraction cool. The XY movement can be synchronized with droplet generation, i.e., movement can occur when droplets 74 are not being ejected from the nozzle 72. A beam of electromagnetic radiation 37 between the electromagnetic radiation source 62 and an electromagnetic radiation sensor 66 intersects the path of the droplets exiting the nozzle 72. The beam of electromagnetic radiation 37 can also cross a transparent tube 68 through which the droplets 74 fall. An aperture 64 can be provided in front of the electromagnetic radiation sensor 66. The droplets ejected from the nozzle 72 are collected by one of the collection vessels 12, 14.

[0078] The XY movement of the dispensing head 31 can be synchronized with droplet formation and droplet ejection in such a way that movement is only performed when droplets are safely attached to the nozzle 72. The movement of the dispensing head from one collection vessel 12, 14 to another can also take into account the flow rate of liquid through the nozzle. An increased flow rate will increase droplet formation, and the time slot for moving the dispensing head will decrease due to the increased droplet formation frequency. Acceleration and deceleration of the dispensing head movement can also be taken into account to predict a safe time slot in which movement can be performed without providing droplets in the desired area, i.e., inside or outside of the collection vessel.

[0079] In one example embodiment, movement of the dispensing head 31 can begin after a droplet 74 is detected. Movement of the dispensing head 31 can, in one example embodiment, only be allowed in time slots that are 50% of the previously registered time between two consecutive droplets. A control unit can control the movement of the dispensing head. The control unit can be pre-programmed for different types of racks 6, 7 to be used, i.e., the number of collection vessels, the distance between the collection vessels, the order in which the collection vessels should be filled, etc. The control unit can also receive information about the frequency of droplets and the detection of droplets to determine when movement of the dispensing head can be performed without endangering any liquid outside the collection vessels.

[0080] FIG. 5 shows a side view of tilted collection vessels 12, 14. The axis of symmetry of collection vessels 12, 14 can be angled relative to the trajectory of droplets 74 from nozzle 72, or alternatively, the collection vessels 12, 14 can be angled at an angle α relative to the normal N to the first plane of movement of the dispensing head 31. The first plane in which the dispensing head moves can be a plane essentially parallel to the tray area 11. Collection vessels can be angled by tilting racks 6, 7 or by providing wells in the racks that are not perpendicular to the bottom surfaces of the racks 6, 7. In various exemplary embodiments, the tray area 11 may not be perpendicular to the trajectory of droplets from nozzle 72. When droplets 74 hit a higher point inside collection vessel 12, they have less energy to exit, and the liquid follows the inside of collection vessel 12 to the collected liquid 88. Any small droplets that are ejected will be directed toward other interior walls of collection vessel 12. When droplets from the nozzle 72 hit the liquid surface 89, small droplets may be ejected from the collection vessel due to the energy displacement. This can lead to liquid deposition not only on the nozzle but also around the collection vessels 12, 14, and in the worst case scenario, in adjacent collection vessels. Using an inclined collection vessel can reduce liquid loss from the fraction, reduce deposition on the nozzle and surroundings, and also reduce the risk of contamination of adjacent fractions.

[0081] The detection mechanism for determining the position of the collection containers 12, 14 can be by a reading mechanism on the arm 3 for reading bar codes provided on the racks 6, 7 or other detection signatures on said racks 6, 7. The racks 6, 7 can be provided in aligned positions on the tray area 11. In a calibrated machine, the XY movement of the machine can be known from reading the codes on which the containers are located.

[0082] FIG. 9 is a front perspective view of an example embodiment of a fraction collector equipped with a cooling means / device according to the present invention. The racks 6, 7 can include a cooling means 60, which includes an enclosed cooling volume containing a cooling medium. The cooling means 60 is shown elevated relative to the tray area 11 for illustrative purposes only. The cooling means 60 can be configured to at least partially surround at least one collection vessel 12, 14. In various example embodiments, the cooling means 60 can be removably attached to the racks 6, 7. In various example embodiments, the cooling means 60 can be in the form of a hollow frame that surrounds the racks 6, 7. The frame may or may not include a base plate. The frame can be a single unit for surrounding multiple racks or a separate unit that surrounds only a single rack. In various example embodiments, the cooling means can be an integral part of the rack, i.e., the rack itself is provided with a hollow structure that is at least partially filled with a cooling medium. Also shown in FIG. 9 are example embodiments of alignment features 92, 94 provided in the tray area 11. The alignment features 92 are in the form of protrusions configured to be received by corresponding recesses (not shown) in the racks 6, 7. The alignment features 94 are in the form of protruding elements configured to receive said at least one rack 6, 7 and limit its movement in the X and / or Y directions. Multiple alignment features can be provided on the tray area to receive different types of racks 6, 7 and / or cooling means 60. The cooling means 60 can be provided in a cold area, such as a cooler or freezer, before use. The cooled cooling means can be removed from the cold area immediately before use to cool the dispensed liquid in the collection containers 12, 14.

[0083] Various embodiments may also be provided that include one or more temperature sensors integrated therein. For example, a temperature sensor may be provided in one or more of the support system, carrier, extension arm, dispense head, tray area, rack, etc.

[0084] Various embodiments may also be provided with a cooling element or system within the rack. For example, an air-cooling system may be provided that provides chilled air to at least one rack and / or collection bin. In various embodiments, a cooling block may be provided that is optionally releasably connectable to at least one rack and / or collection bin. Such a cooling block may be manufactured, for example, by 3-D printing and may be filled / fillable with a cooling fluid such as water. The present invention is not limited to the embodiments described above and shown in the drawings, which are primarily for purposes of illustration and description. This patent application is intended to cover all adaptations and modifications of the preferred embodiments described herein, and therefore the present invention is defined by the language of the appended claims and their equivalents. Accordingly, the device may be modified in any manner within the scope of the appended claims.

[0085] Throughout this specification and the claims that follow, unless the context otherwise requires, the word "comprise" and variations such as "comprises" or "comprising" will be understood to mean the inclusion of a stated integer or step or group of integers or steps, but not to the exclusion of any other integer or step or group of integers or steps. [Explanation of symbols]

[0086] 1 Bottom Frame 2 Mainboard Housing 2' Mainboard Base 2'' Mainboard Cover 3 Arm 3' Cover 4 Tube Rack 4' Frame 4'' top plate 5 Distance Plate 6 racks 7 Rack 8 Flow-through Tubes 8' flow-through hole 9 Home Tube 9' Home Hole 11 Tray Area 12 Collection container 14 Collection containers 20 Capillary 30 Connection part 31 Dispensing Head 32 Cover 33 Housing 34 Support 35 Exit passage 37 Electromagnetic Radiation Pathways 40 Linear Bearing Y Rail 41 Linear bearing Y slide unit 42 Career 44 pin 45 Groove 47 Support structure 50 Linear Bearing X-Rail 60 Cooling means 62 Electromagnetic radiation sources 64 aperture 66 Electromagnetic radiation sensor 68 Transparent Pipe 72 nozzles 74 Droplets 77 Aperture 88 liquid 89 Liquid level 92 Alignment Features 94 Alignment Features 100 Fraction Collector

Claims

1. a. a support system (1, 2); b. a carrier (42) movably supported by said support system (1, 2); c. an extension arm (3) connected to the carrier (42); d. at least one dispensing head (31) for dispensing droplets, said at least one dispensing head (31) being movably connected to said extension arm (3), said dispensing head (31) and carrier (42) being configured to move relative to said support system (1, 2) in a first plane; e. a tray area (11) designed to support at least one rack (6, 7), said at least one rack (6, 7) designed to contain at least one collection container (12, 14), movement of said carrier (42) being achieved by a linear bearing Y-slide unit (41), said linear bearing Y-slide unit (41) configured to move along a linear bearing Y-rail (40), said carrier (42) being attached to the underside of said linear bearing Y-slide unit (41); A fraction collector device (100) comprising:

2. 2. The fraction collector device (100) according to claim 1, wherein the linear bearing Y-rail (40) is positioned in a Z-direction position lower than a top surface of the at least one rack (6, 7) arranged on the tray area (11).

3. 3. The fraction collector device (100) according to claim 1, wherein the racks (6, 7) comprise cooling means (60) comprising an enclosed cooling volume containing a cooling medium, the cooling means (60) being configured to at least partially surround at least one collection vessel (12, 14).

4. 4. The fraction collector device (100) according to claim 1, wherein the dispensing head (31) comprises a transmitter (62) and a receiver (66) for detecting the droplets (74), and a communication path (37) between the transmitter (62) and the receiver (66) crosses the path of the droplets (74).

5. 5. The fraction collector device (100) of claim 4, further comprising an aperture (64) in front of the receiver (66).

6. 6. The fraction collector device (100) of claim 4 or 5, wherein the transmitter (62) is a source of electromagnetic radiation and the receiver (66) is an electromagnetic radiation sensitive sensor.

7. 7. The fraction collector device (100) according to any one of claims 1 to 6, wherein the dispensing head (31) further comprises a tube (68) that is wider than the droplets (74) and made of a material that is transparent to electromagnetic radiation, and wherein the droplets (74) from the dispensing head (31) are dispensed through the tube (68).

8. The fraction collector device (100) of claim 7, wherein the communication path (37) between the transmitter and receiver is transmitted across the tube (68).

9. 9. The fraction collector device (100) according to claim 7 or 8, wherein the tube (68) is made of a transparent material.

10. 10. The fraction collector device (100) of any one of claims 1 to 9, wherein the tray area (11) is configured to support at least two racks (6, 7) of collection vessels (12, 14).

11. 11. The fraction collector device (100) of any one of claims 1 to 10, wherein the collection vessels (12, 14) are angled relative to a normal to the first plane.

12. 12. A fraction collector device (100) according to any one of claims 1 to 11, wherein the movably supported carrier (42) and / or the movably connected dispensing head (31) are provided with a splash cover (3', 32) configured to prevent liquid splashes emerging from the at least one collection vessel (12, 14) from entering the linear movement mechanism of the carrier (42) and / or the dispensing head (31).

13. 13. The fraction collector device (100) according to any one of claims 1 to 12, wherein the electronics in the dispensing head (31) are provided in a waterproof housing.

14. 14. The fraction collector device (100) according to any one of claims 1 to 13, wherein the dispensing head (31) is assembled by snap-fit.

15. 15. The fraction collector device (100) according to any one of claims 1 to 14, wherein the dispensing head (31) is removably coupled.

16. 16. The fraction collector device (100) according to any one of claims 1 to 15, further comprising one or more of an air cooler, a cooling block and one or more temperature sensors.

17. A method for operating a fraction collector device (100), comprising: a. providing a carrier (42) movably supported by a support system; b. providing an extension arm (3) connected to the carrier (42), wherein at least one dispensing head (31) for dispensing droplets is movably connected to the extension arm, the dispensing head (31) and the carrier (42) being configured to move relative to the support system in a first plane; c. providing a detection device (66) configured to detect the droplets from the dispensing head (31); d. moving the dispensing head (31) in synchronization with the droplets (74) from the dispensing head (31) so that the droplets (74) enter at least one collection container (12, 14) provided on the tray area (11), wherein the movement of the carrier is achieved by a linear bearing Y-slide unit (41), the linear bearing Y-slide unit (41) is configured to move along a linear bearing Y-rail (40), and the carrier (42) is attached to the underside of the linear bearing Y-slide unit (41); A method comprising:

18. e. providing said linear bearing Y-rail (40) in a Z-direction position below a top surface of a rack disposed above said tray area (11) designed to hold said at least one collection container; 18. The method of claim 17, further comprising:

19. f. cooling the at least one collection vessel (12, 14) with a cooling device (60) including an enclosed cooling volume containing a cooling medium configured to at least partially surround the at least one collection vessel; 19. The method of claim 17 or 18, further comprising:

20. g. detecting the droplets (74) by transmitting electromagnetic radiation across the droplet path (68) to an electromagnetic radiation sensitive sensor; h. restricting said electromagnetic radiation passing through an aperture (64) before being detected by said electromagnetic radiation sensitive sensor; 20. The method of any one of claims 17 to 19, further comprising:

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