MODULAR IRRADIATION DEVICE AND IRRADIATION METHOD

Abstract

The invention relates to a modular irradiation device having a main module and at least one support cassette, the support cassette being insertable into a receptacle of the main module. The support cassette has at least one pump, and the main module has at least one pump actuator, these being arranged such that the pump is actuatable with the pump actuator when the support cassette is inserted into the receptacle of the main module.

Claims

1-25. (canceled)

26. A modular irradiation device, comprising: a main module and at least one carrier cassette, wherein the at least one carrier cassette comprises: an exposure surface, on which the at least one irradiation line runs, wherein a fluid to be irradiated is conductible in the at least one irradiation line, and at least one pump, which is connected via a first fluid line to the at least one irradiation line; and the main module comprises: at least one receptacle in which the at least one carrier cassette can be inserted so as to be removable without destruction, and at least one pump actuator, which is arranged so as to be able to actuate the at least one pump when the at least one carrier cassette is inserted into the corresponding receptacle.

27. The modular irradiation device according to claim 26, wherein the at least one carrier cassette comprises at least one further pump which is connected via a second fluid line to the irradiation line.

28. The modular irradiation device according to claim 26, wherein the pump actuator comprises a pump coupling element, which is arranged so as to become engaged with a movable element of the corresponding at least one pump in a form-locked manner when the cassette is inserted into the main module.

29. The modular irradiation device according to claim 26, wherein the at least one carrier cassette comprises at least one valve, which is arranged in at least one of the fluid lines and by way of which a fluid flow between the corresponding pump, which is connected via this fluid line to the irradiation line, and the irradiation line can be controlled, and the main module comprises a respective valve actuator for one, several or all of the at least one valves, the valve actuators are in each case arranged so as to be able to adjust the corresponding valve when the at least one carrier cassette is arranged in the corresponding receptacle.

30. The modular irradiation device according to claim 29, wherein the at least one valve comprises a stopcock by way of which the valve can be adjusted for controlling the flow of fluid, the corresponding valve actuator comprising a coupling element, which can be coupled to the stopcock in such a way that a force adjusting the valve or a torque adjusting the valve can be exerted on the stopcock by way of the valve actuator, wherein the coupling element is arranged so as to become engaged with the stopcock when the carrier cassette is inserted into the main module.

31. The modular irradiation device according to claim 29, wherein the at least one valve comprises or is a three-way valve having three ports, one of the fluid lines is connected to a first of the ports, the at least one pump is connected to a second of the ports, and the further pump is connected to the third of the ports.

32. The modular irradiation device according to claim 26, wherein the at least one pump comprises a fluid chamber and a plunger, the plunger sealing the fluid chamber in a fluid-tight manner and being displaceable in the fluid chamber, the at least one pump actuator engaging on the plunger of the pump when the at least one carrier cassette is inserted into the corresponding receptacle, and a force being applicable in a displacement direction of the plunger by way of the pump actuator.

33. The modular irradiation device according to claim 26, wherein the at least one pump is a syringe.

34. The modular irradiation device according to claim 27, wherein the carrier cassette comprises three pumps that are connected to the second fluid line, and two pumps that are connected to the first fluid line.

35. The modular irradiation device according to claim 26, wherein the main module includes a main module surface, and the exposure surface of the carrier cassette and the main module surface are coplanar when the carrier cassette is inserted into the corresponding receptacle of the main module.

36. The modular irradiation device according to claim 26, wherein the main module comprises exactly one actuator for each pump that is connected to one of the fluid lines, the corresponding pump being actuatable by way of the actuator.

37. The modular irradiation device according to claim 27, wherein the main module comprises two movable and/or foldable side parts.

38. The modular irradiation device according to claim 26, wherein the carrier cassette comprises a fluid chip, the fluid chip comprising a base body, the base body including a base body exposure surface in which the at least one irradiation line is formed, the at least one irradiation line being a channel structure including at least one channel, the base body furthermore comprising a first fluid connection to which the first fluid line is connected, and a second fluid connection to which the second fluid line is connected, the base body additionally comprising a film, which is arranged on the base body exposure surface and covers the channel structure, the film sealing the channel structure against egress of fluid onto the base body exposure surface.

39. The modular irradiation device according to claim 38, wherein the channel structure includes a multitude of the channels, which converge at the respective ends thereof in the respective fluid connection.

40. The modular irradiation device according to claim 39, wherein the channels at their ends respectively converge in pairs into combined channels, and the combined channels, in turn, converge in each case in pairs into combined channels until exactly two combined channels converge into one of the fluid connections.

41. The modular irradiation device according to claim 38, wherein the base body is a monolithic block into which the channel structure is embossed and/or cut.

42. The modular irradiation device according to claim 38, wherein the film has a thickness of smaller than or equal to 80 m.

43. The modular irradiation device according to claim 38, wherein a depth of the at least one channel is smaller than or equal to 300 m.

44. An irradiation method for irradiating a fluid in a modular irradiation device according to claim 26, inserting into the main module at least one of the carrier cassettes, and irradiating the exposure surface of the at least one carrier cassette with an ionizing radiation, while moving the fluid to be irradiated through the at least one irradiation line, and removing the carrier cassette from the main module.

45. The irradiation method according to claim 44, wherein at least one further carrier cassette is inserted into the main module once or several times after the respective preceding carrier cassette has been removed from the main module, and the exposure surface of the at least one further carrier cassette is irradiated with ionizing radiation, while a fluid to be irradiated is moved through the at least one irradiation line of this further carrier cassette.

46. The irradiation method according to claim 44, wherein a disinfecting agent is moved through the channel structure of the fluid chip after the at least one carrier cassette has been inserted into the main module, and before the fluid to be irradiated is moved through the irradiation line.

47. The irradiation method according to claim 44, wherein a cell medium is moved into the channel structure after the at least one carrier cassette has been inserted into the main module, and before the fluid to be irradiated is moved through the irradiation line, and/or after the fluid to be irradiated was moved through the channel structure.

48. The irradiation method according to claim 44, wherein the fluid transport through the irradiation line is effectuated in that the corresponding of the pumps generates negative pressure.

49. The irradiation method according to claim 44, wherein the fluid to be irradiated comprises or is a cell suspension, virus suspension, medium, serum and/or blood sample.

50. The irradiation method according to claim 44, wherein the ionizing radiation is electrons or UV radiation.

Description

[0047] In the drawings:

[0048] FIGS. 1A, B, C show a modular irradiation device;

[0049] FIGS. 2A, B, C show a modular irradiation device;

[0050] FIGS. 3A, B, C show a carrier cassette including some elements of a main module;

[0051] FIGS. 4A, B, C show a carrier cassette including elements of the main module;

[0052] FIGS. 5A, B show a carrier cassette;

[0053] FIGS. 6A, B show a fluid chip;

[0054] FIGS. 7A, B, C show an exemplary schematic device in which a method for irradiating a fluid can be carried out;

[0055] FIG. 8 shows an exemplary schematic device in which a method for irradiating a fluid can be carried out;

[0056] FIG. 9 shows an exemplary schematic device in which a method for irradiating a fluid can be carried out; and

[0057] FIG. 10 shows an exemplary schematic device in which a method for irradiating a fluid can be carried out.

[0058] FIGS. 1A, B, C show a modular irradiation device according to the invention, comprising a main module 1 and a carrier cassette 2. In FIG. 1A, the carrier cassette 2 is not arranged in the main module and therefore not shown. In FIGS. 1B and C, the carrier cassette 2 is inserted into a receptacle 3 of the main module. FIGS. 2A, B and C each show the irradiation device of FIG. 1 in a side view. The carrier cassette 2 has an exposure surface 4 on which the at least one irradiation line 13 runs, which is apparent in FIGS. 3, 4 and 5. A fluid to be irradiated can be conducted through the irradiation line 13.

[0059] The carrier cassette 2 furthermore comprises at least one pump 5a, 5b, which is connected via fluid lines to the irradiation line 13. In addition to the receptacle 3, into which the carrier cassette 2 can be inserted so as to be removable without destruction, the main module 1 comprises at least one pump actuator 6a, 6b for each of the pumps 5a, 5b, by way of which the corresponding of the pumps 5a, 5b can be actuated when the carrier cassette 2 is inserted into the receptacle 3. In the example shown in FIGS. 1 and 2, two pumps 5a, 5b are provided, which are configured as syringes here. Accordingly, the main module 2 comprises the actuators 6a, 6b, which are linear actuators here.

[0060] FIGS. 1A and 2A show the main module in each case without the inserted carrier cassette 2. FIGS. 1B and 2B show the main module 1 in each case with the inserted carrier cassette 2. In these examples, the main module 1 comprises two foldable side parts 7a, 7b, which comprise valve actuators 8a, 8b and the linear actuators 6a and 6b. The carrier cassette 2 moreover comprises valves including valve stopcocks 9a, 9b, by which a fluid flow between the pumps 5a, 5b and the irradiation line 13 can be controlled. The linear actuators 6a, 6b and the valve actuators 8a and 8b are arranged at the main module 1 so as to engage on the pumps 5a, 5b and the valve stopcocks 9a, 9b, so that these can be actuated, when the side parts 7a, 7b are being closed after the carrier cassette 2 has been inserted. In the example shown in FIGS. 1C and 2C, the pump 5a is operated by the actuator 6a, while the pump 5b is not actuated, but serves as a reservoir for fluid. The actuator 6b actuates a pump (not shown in the figures) that is arranged behind the pump 5a.

[0061] The pumps 5a, 5b are configured as syringes here, each including a plunger running in a cylindrical cylinder. In the example shown, the syringes are arranged having a vertical plunger movement direction and open with the outlet openings thereof into the valves 9a, 9b at the upper end.

[0062] The main module 1 is configured as a linkage including four parallel rods, which are vertically positioned and carry a main module surface 10, which closes the main module toward the top. The carrier cassette 2 has an exposure surface 11, which is coplanar with respect to the main module surface 10 when the carrier cassette 2 is inserted into the receptacle 3. The foldable side parts 7a, 7b are arranged at the parallel rods of the main module 1 and rotatable thereabout so as to be folded into the closed state shown in FIGS. 1C and 2C.

[0063] FIGS. 3A, 3B and 3C, by way of example, show a carrier cassette 2 as shown in FIGS. 1 and 2 in detail. The carrier cassette comprises four pumps 5a, 5b, 5c, 5d here, of which three are visible. The pumps are again configured as syringes. The pumps 5b and 5c are connected via valves 9a and 9b and a fluid line 12 to an irradiation line 13, which is configured as a channel structure in a fluid chip 14 here. The carrier cassette comprises a support structure 15 here, in which the syringes 5a, 5b, 5c, 5d are removably inserted. The cylinder axes of the syringes 5a, 5b, 5c, 5d are situated parallel to one another.

[0064] The valves 9a, 9b are three-way valves here, which can be adjusted by valve stopcocks. FIGS. 3A, 3B, 3C show valve actuators 8a, 8b, which via coupling elements can engage on stopcocks of the valves 9a, 9b and can rotate these. The actuators 8a, 8b are rotating actuators. The actuators 8a, 8b are not part of the carrier cassette 2, but are part of the main module 1, the other components of which are not shown in FIG. 3 for the sake of clarity. FIGS. 3A, 3B and 3C show the valve actuators 8a, 8b in different positions relative to the valves 9a, 9b. These positions form the closing of that side part of the foldable side parts 7b at which the valve actuators 8a, 8b are arranged. FIG. 3C shows the closed state as well as, indicated by arrows, the rotating actuation of the valves 9a, 9b by the valve actuators 8a, 8b. The valve actuators 8a, 8b transmit the torque onto the valves 9a, 9b in a form-locked manner. In the example shown, the coupling elements of the valve actuators 8a, 8b can have a negative shape of the stopcocks of the valves 9a, 9b. However, it shall be noted that the valves can also be adjusted pneumatically, hydraulically, electrically, magnetically or in another manner. The use of rotatable valves is also only an exemplary option.

[0065] FIGS. 4A, 4B, 4C show the carrier cassette shown in FIG. 3 rotated 90 about a vertical axis. As a result, the pump 5d, which is not apparent in FIG. 3 and which is arranged next to the other pumps 5a, 5b, 5c parallel thereto, becomes visible. Additionally, a valve 9c is apparent here, via which the pump 5a is connected to the irradiation line 13. Unless stated otherwise here, the description for FIG. 3 also applies to FIG. 4.

[0066] In addition to the carrier cassette 2, FIG. 4 shows elements 6a, 6b that are part of pump actuators and therefore part of the main module 1. Of the main module 1, only the components of the valve actuators 6a, 6b that engage on the pumps are shown here, while all other components of the main module 1 are hidden for the sake of clarity. FIGS. 4A, 4B and 4C show the positions of the pump actuators 6a, 6b relative to the carrier cassette 2 as the foldable side part 7a of the main module is being closed.

[0067] The pump actuators 6a and 6b each have a recess 61a and 61b. The syringe 5a has an end face 51a that protrudes over a plunger rod of the plunger of the syringe 5a. The smaller syringe 5e accordingly has an end face 51e that projects beyond the plunger of this syringe. Over the course of FIGS. 5A to 5C, the side part 7a is being closed, and the actuators 6a, 6b move toward the syringes 5e and 5a. In the closed state shown in FIG. 4C, the opening 61a of the actuator 6a engages behind the end face 51e of the syringe 5e so that the syringe can be filled by the actuator 6a, as is indicated by the arrow in FIG. 4C. At the same time, the recess 61b of the actuator 6b engages behind the end face 51a of the syringe 5a so that the syringe 5a can be filled by this actuator, as is identified in FIG. 4C by the corresponding arrow.

[0068] FIGS. 5A and 5B show the carrier cassette shown in FIGS. 3 and 4 again in an enlarged form, in a perspective view and in a side view. The syringe 5a is connected by way of the three-way valve 9c to the fluid line 12a, which, in turn, is connected to a fluid connection of the fluid chip 12 into which the irradiation line 13 is introduced. The syringe 5d is connected via a further fluid line 12b. With respect to the further design, reference shall be made to the description of FIGS. 3 and 4.

[0069] FIG. 6, by way of example, shows a fluid chip 14, as it may be used in FIGS. 1 to 5. The fluid chip 14 can be produced as a monolithic block, for example from polyethylene, into which the irradiation line 13 is embossed or cut. The fluid chip 14 has a base surface exposure surface 16 into which the irradiation line 13 is embossed in the form of a channel structure. The channel structure 13 ends at the fluid connections 15a and 15b. Proceeding from the fluid connection 15a, the channel structure initially splits into two channels, which each in turn split into two channels. Each of these then splits yet again into two channels and they open in this way into a total of eight parallel, straight channel sections. At the opposite end, the straight channel sections combine again in pairs until they open into the shared fluid connection 15b. In the example shown, the fluid connections 15a and 15b are guided out of the fluid chip downwardly in a direction that is perpendicular to the base body exposure surface 16, that is, in the direction away from the base body exposure surface 16, and can be connected there to the fluid lines 12a, 12b. In the example shown, the base body exposure surface 16 is covered with a film 17, which seals the channel structure 13 to prevent the egress of fluid onto the base body exposure surface 16.

[0070] FIGS. 7A, 7B, 7C and 7D, by way of example, show how a method according to the invention can be carried out in the modular irradiation device of the invention. For the sake of clarity, FIGS. 7A, B, C, D only show the syringes 5a, 5b, 5c, 5d, 5e, the valves 9a, 9b, 9c and the fluid chip 14 including the irradiation line 13. These elements can be configured as shown in FIGS. 1 to 6. The arrangement of the elements in FIG. 7 here shall only be understood to be schematically functional.

[0071] The valves 9a, 9b, 9c are three-way valves here, by way of which it is possible to switch which of the syringes 5a to 5e is connected to the fluid chip 14 in a fluid-conducting manner. The syringes 5a and 5b are connected by way of the three-way valve 9a via a first fluid line 12a to a first fluid connection of the fluid chip 14, and the syringes 5c, 5d, 5e are connected by way of the three-way valves 9b and 9c by means of a second fluid line 12b to a second fluid connection of the fluid chip 14.

[0072] Hereafter, it shall be assumed that the syringe 5a is used to receive the irradiated fluid, the syringe 5b is used to receive waste fluid, the syringe 5c contains a cell suspension, the syringe 5d contains a cell medium, and the syringe 5e contains a disinfecting agent, such as ethanol, for example.

[0073] After the microfluid chip 14 has been produced and sealed, microbes and the like may be present in the irradiation lines 13. The fluid chip 14 should therefore advantageously be disinfected. For this purpose, as shown in FIG. 7A, the three-way valve 9a is switched so as to establish a connection between the waste syringe 5b and the fluid chip 14. Moreover, the three-way valves 9b and 9c are configured so as to close the syringes 5c and 5d and establish a fluid-conducting connection between the syringe 5e and the fluid chip 14. The syringe 5b is now being filled, whereby fluid, this being the disinfecting agent, is suctioned out of the syringe 5e and conducted through the fluid chip 14.

[0074] In the next step shown in FIG. 7B, the position of the three-way valve 9a remains unchanged, so that the waste syringe 5b continues to be connected to the fluid chip 14. The three-way valve 9c, by way of which the syringe 5d is connected to the fluid chip, is positioned in such a way that the syringe 5d is connected to the fluid chip 14 in a fluid-conducting manner. The position of the three-way valve 9b at the syringe 5c remains unchanged. The waste syringe 5b now continues to be filled further, as a result of which fluid, this being cell medium here, is suctioned out of the syringe 5d into the fluid chip 14 and through the same.

[0075] In the next step shown in FIG. 7C, the valve stopcock 9a at the first fluid line 12a is now positioned in such a way that the syringe 5a is connected to the first fluid line 12a, and thus to the irradiation line 13 in the fluid chip 14, in a fluid-conducting manner. Moreover, the three-way valve 9b is positioned in such a way that the syringes 5d and 5e are cut off the second fluid line 12b, and the syringe 5c including the cell suspension is connected to the irradiation line 13 in a fluid-conducting manner. Moreover, an irradiation source 18 is activated, which emits radiation onto the exposure surface and the irradiation line 13. Meanwhile, the syringe 5a is being filled, whereby cell suspension from the syringe 5c is suctioned through the fluid chip 14 and received in the syringe 5a. After the irradiation has been completed, the three-way valve 9b can optionally be configured in such a way that the syringe 5d is again connected to the irradiation line 13. In this way, by further filling the syringe 5a, the channel structure 13 can be rinsed with cell medium so as to rinse as many of the irradiated cells as possible from the fluid chip 14 into the syringe 5a.

[0076] If needed, the fluid chip 14 can subsequently be rinsed with ethanol from the syringe 5e again. The configuration, in turn, corresponds to that shown in FIG. 7A. The syringe 5b is again filled, whereby disinfecting agent is suctioned from the syringe 5e through the fluid chip 14.

[0077] FIG. 8, by way of example, shows a very simple embodiment of the invention in which only one syringe 5a for the irradiated sample and one syringe 5b for cell suspension are provided. The syringe 5a is connected via a first fluid line 12a to a fluid connection of the fluid chip 14, and the syringe 5b is connected via a fluid line 12b to a second fluid connection of the fluid chip 14. In this embodiment, it is not necessary for the irradiation device to comprise valves. All that is needed for irradiation is to activate the irradiation source 18 (not shown here) and to then fill the syringe 5a, whereby cell suspension from the syringe 5b is transported through the channel structure 13 into the syringe 5a.

[0078] FIG. 9 shows another simple embodiment of the invention, wherein again only one syringe 5a for the irradiated sample is arranged at the first fluid connection of the fluid chip 14 via the fluid line 12a. A syringe 5b including cell suspension on the one hand and a syringe 5c including cell medium on the other hand are connected via the second fluid line 12b and a three-way valve 9b to the second fluid connection. Similarly to what is shown in FIG. 7, cell suspension can initially be suctioned from the syringe 5b through the fluid chip 14 by filling the syringe 5a. For this purpose, the three-way valve is switched so as to establish a connection between the syringe 5b and the fluid connection of the fluid chip 14. Subsequent to the irradiation, the three-way valve 9b can then be switched so as to establish a connection between the syringe 5c including cell medium and the fluid chip 14, while closing the syringe 5b. If the syringe 5a is then filled further, the channel structure 13 of the fluid chip 14 is rinsed with cell medium, and in this way as many cells as possible are removed from the channel structure 13.

[0079] FIG. 10 shows a variant of the situation shown in FIG. 7. FIG. 10 differs from FIG. 7 in that, instead of the syringe 5d in FIG. 7, an arrangement of four syringes 5ca, 5cb, 5cc and 5cd is arranged at the corresponding valve 9b, which is connected by way of three-way valves 59a, 59b, 59c to the valve 9b. Different suspensions can be provided in the syringes 5ca, 5cb, 5cc, which can be conducted through the channel structure 13. Using a syringe 5cd, moreover cell suspension can additionally be provided, which can be used to rinse the system connected to the valve stopcock 9b. By positioning the valves 59a, 59b, 59c, the syringes 5ca, 5cb, 5cd and 5cd can be selectively connected to the valve 9b. The method can then be carried out analogously to that shown in FIG. 7.

[0080] The invention allows safe and sterile irradiation of fluids. For example, the microfluid chip 14 can be produced from polyethylene as an injection-molded part and subsequently be sealed with a PET/PE film. The sealing with a thin film (for example <60 m) helps to ensure that only a small portion of the radiation is absorbed by the film. All components that come in contact with the cell suspension can advantageously be designed as disposable parts, in particular the fluid chip 14 and the syringes 5. As a result of the modular concept including a main module and a carrier cassette, it is possible to produce multiple carrier cassettes and to load them in parallel. In this way, the process preparation becomes parallelizable. It is possible to automatically vent the system so as to avoid possible elasticities and changes in flow associated therewith. The paths between the pumps and the irradiation line are preferably kept short, so that no additional elasticities, for example due to silicone hoses, arise, which could result in changes in the flow rate. Moreover, the dead volume can be kept small, which is a major advantage when producing personalized medicine. The layer thickness and the flow rate of the fluid in the irradiation line can be precisely set and controlled.