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WO-2026093545-A1 - CELL AVIDITY ANALYSIS APPARATUS

WO2026093545A1WO 2026093545 A1WO2026093545 A1WO 2026093545A1WO-2026093545-A1

Abstract

The invention is directed to Cell avidity analysis apparatus (100). The apparatus comprises a housing (110) for housing components of the apparatus (100). The apparatus comprises a centrifuge unit (200) located inside the housing (110). The centrifuge unit (200) is arranged for holding and centrifuging a sample holder (802), preferably a sample holder (802) held within a substantially hermetically sealed casing (803). The apparatus also comprises an imaging device (300), preferably a microscopy device, for imaging at least a first section of the sample holder (802), preferably said first section being formed by a section of a flow channel (851, 852, 853) of said sample holder (802). The imaging device (300) is located inside the housing (110) and outside the centrifuge unit (200). The apparatus (100) further comprises a handling system (400) located inside the housing (110). The handling system (400) is arranged for placing the sample holder (802) inside the centrifuge (200) and/or arranged for taking the sample holder (802) out of the centrifuge (200) and towards the imaging device (300).

Inventors

  • VAN LOENHOUT, Marinus Theodorus Johannes
  • DAVOLI, Serena Alba
  • VAN DAM, Bart
  • DE SÁ VIVAS, Aisen Gabriel

Assignees

  • LUMICKS CA HOLDING B.V.

Dates

Publication Date
20260507
Application Date
20251031
Priority Date
20241031

Claims (15)

  1. 1. Cell avidity analysis apparatus (100), comprising: a housing (110) for housing components of the apparatus (100); a centrifuge unit (200) located inside the housing (110), said centrifuge unit (200) being arranged for holding and centrifuging a sample holder (802), preferably a sample holder (802) held within a substantially hermetically sealed casing (803); and an imaging device (300), preferably a microscopy device, for imaging at least a first section of the sample holder (802), preferably said first section being formed by a section of a flow channel (851 , 852, 853) of said sample holder (802), wherein said imaging device (300) being located inside the housing (110), wherein said imaging device (300) is located outside the centrifuge unit (200), and wherein the apparatus (100) further comprises a handling system (400), the handling system (400) being located inside the housing (110), and the handling system (400) being arranged for placing the sample holder (802) inside the centrifuge (200) and/or arranged for taking the sample holder (802) out of the centrifuge (200) and towards the imaging device (300).
  2. 2. Cell avidity analysis apparatus (100) according to claim 1 , wherein the apparatus (100) comprises a first sample holder support (501), the first sample holder support (501) being located inside the housing (110), and the first sample holder support (501) being for supporting the sample holder (802) when the imaging device is imaging at least the first section of the sample holder (802), wherein the handling system (400) is arranged for removing the sample holder (802), in particular when held in the casing (803), from the centrifuge unit (200) and placing the sample holder (802) at, on and/or in the first sample holder support (501).
  3. 3. Cell avidity analysis apparatus (100) according to claim 2, wherein the first sample holder support (501) being provided with a first stop surface or abutment against which the sample holder (802) can rest, said sample 37 holder further being provided with an opposing element arranged for applying pressure or force against the sample holder such as to press in against said first stop surface; and/or wherein the first sample holder support (501) and the imaging device (300) are movable with respect to each other in order to enable bringing a respective one of multiple sections of the sample holder (802), preferably multiple sections of multiple ones of multiple flow channels (851 , 852, 853) of the sample holder (802), into a field of view of the imaging device (300); and/or wherein the handling system (400) is arranged for turning the sample holder (802) upside down, preferably when said sample holder (802) is not located inside the casing (803), if any.
  4. 4. Cell avidity analysis apparatus (100) according to any one of the preceding claims wherein the apparatus (100), preferably its handling system (400), is arranged for removing the sample holder (802) from the casing (803).
  5. 5. Cell avidity analysis apparatus (100) according to any one of the preceding claims, wherein the sample holder (802) comprises at least one flow channel (851), and preferably multiple flow channels (851 , 852, 853), each extending between a respective channel inlet (851A, 852A, 853A) and a respective channel outlet (851 B, 852B, 853B), wherein the apparatus (100) further comprises a loading station (700), located inside the housing (110), wherein the loading station (700) is provided with a second sample holder support for holding the sample holder (802), which for instance may be present in an opened casing (803) or part (831) of said casing (803), more preferably a casing of which a second casing part (832), which may form a lid of the casing, has been temporarily removed, and wherein the loading station (700) is further provided with at least one liquid handling module (710), such as for example a pipetting robot, said at least one liquid handling module (710) being located inside the housing (110), said liquid handling module (710) being arranged for loading a liquid into at least one of the one or multiple flow channels (851 , 852, 853) of the sample holder (802), for instance a sample holder in the form of a 96-well, 384-well or 1536-well microplate conforming to the ANSI SLAS standards, preferably wherein the liquid handling module comprise at least one set including a liquid dispenser for liquid insertion into the flow channel and a liquid remover for liquid removal from said flow channel, in particular wherein the liquid handling module (710) is arranged such that said liquid dispenser can dispense into the channel inlet (851A, 852A, 853A) while said liquid remover simultaneously aspirates from the channel outlet (851 B, 852B, 853B) of the same flow channel (851 , 852, 853), for example in particular to facilitate achieving a relatively constant flow and/or facilitate counteracting overflow or emptying of said flow channel, and/or preferably wherein the loading station (700) is arranged to load liquid into multiple ones of multiple flow channels (851 , 852, 853) of the sample holder (802) at least partly simultaneously, more preferably wherein the multiple ones comprise at least four flow channels, more preferably at least eight flow channels.
  6. 6. Cell avidity analysis apparatus (100) according to any one of the preceding claims, wherein the centrifuge unit (200) comprises a rotor (210) provided with multiple receptacles (220, 230), each one of which is arranged for receiving and holding a sample holder (802), preferably a sample holder held within a cassette’s casing (803) said receptacles (220, 230) being arranged equidistantly and/or rotationally symmetrically about the rotational axis (211) of the rotor (210), preferably wherein each receptacle (220, 230)is hingedly mounted with respect to the rotor (210) in order to enable to hinge or swing about a hinging axis (A220, A230), said hinging axis extending transverse to the rotational axis (211) of the rotor (210) and more preferably also extending substantially tangential to a virtual circle surrounding said rotor (210).
  7. 7. Cell avidity analysis apparatus (100) according to claim 6, wherein each of the receptacles (220, 230) comprises a tray (221 , 231) for receiving and holding the respective sample holder (802), which preferably may be part of a cell avidity analysis cassette (801), and the centrifuge unit (200) is arranged such that, in a rest position of the centrifuge (200), said tray (220, 230) extends in a substantially flat or horizontal position; and/or wherein at least one of the receptacles (220, 230) holds a releasably received counterweight, preferably one substantially dimensioned and/or substantially shaped as the casing (803) of the sample holder (802).
  8. 8. Cell avidity analysis apparatus (100) according to any one of the preceding claims, wherein said apparatus (100) further comprises an opening device (600) arranged for opening a casing (803) which houses the sample holder (802), said opening device being located inside the housing (110) of the apparatus (100), wherein the opening device is arranged for receiving and engaging a first casing part (831) of the casing (803), wherein the apparatus (100), for instance its handling system (400), is arranged for engaging a second casing part (832) of the casing (803) and removing the second casing part (832) from the first casing part (831), preferably wherein the opening device (600) is further provided with an opening mechanism (610) for unlocking one or multiple locks (804) or locking mechanisms (804), if any, for releasably locking the first casing part (831) with respect to the second casing part (832).
  9. 9. Cell avidity analysis apparatus (100) according to claim 8, wherein the opening mechanism (610) comprises at least one, and preferably at least three, such as for instance four, push elements (611 , 612, 613, 614), preferably push rods, for unlocking or disengaging a respective lock (804) formed as a releasable snap lock (840).
  10. 10. Cell avidity analysis apparatus (100) according to any one of the preceding claims, wherein the apparatus (100) further comprises one or more storage racks (910) for storing a sample holder, preferably for storing a cassette (801) comprising a casing (803) housing the sample holder (802) therewithin, said one or more storage racks (910) being located inside the housing (110) of the apparatus (100), and wherein the handling system is arranged to move the sample holder (802), preferably the cassette provided with said sample holder, from the storage rack (910) to the loading station and/or the opening device (600), if any, which opening device (600) may be part of the loading station (700), and/or wherein the handling system (400) is arranged to move the sample holder, preferably the cassette (901) provided with said sample holder, from the loading station (700) and/or the opening device (600), if any, which opening device may be part of the loading station, to the storage rack (910).
  11. 11. Cell avidity analysis apparatus (100) according to any one of the preceding claims, wherein the handling system (400) is arranged to move the sample holder, preferably the cassette provided with said sample holder, from the loading station and/or the opening device to the first sample holder support and/or vice versa, and/or wherein the handling system (400) is arranged to move the sample holder, preferably the cassette provided with said sample holder, from the centrifuge unit (200) to the first sample holder support (501) and/or vice versa, and/or wherein the handling system (400) is arranged to move the sample holder, preferably the cassette (801) provided with said sample holder, from the centrifuge unit (200) to the storage rack (910) and/or vice versa, and/or wherein the handling system (400) is arranged to move the sample holder, preferably the cassette provided with said sample holder, from the centrifuge unit (200) to the loading station (700) and/or the opening device (600) and/or vice versa, and/or wherein the handling system (400) is arranged to move the sample holder, preferably the cassette provided with said sample holder (802), from the storage rack (910) to the first sample holder support (501) and/or vice versa.
  12. 12. Cell avidity analysis apparatus (100) according to any one of the preceding claims, further comprising at least one of a heater or a cooler for adapting and/or 41 controlling the temperature in at least a part or section (900) of the apparatus (100), preferably for at least adapting and/or controlling the temperature in a part or section in which the storage rack (910) is provided.
  13. 13. Cell avidity analysis apparatus (100) according to any one of the preceding claims, wherein the apparatus comprises a non-transitory computer-readable medium with instructions encoded thereon, and one or multiple processors configured to, when executing the instructions, perform the operations of: inverting the sample holder, in particular by means of the handling system (400), from a starting position, such as an upside up position, of the sample holder (802) into an inverted position, such as for example the upside down position of the sample holder, preferably while the sample holder (802) is inside the casing (803); and timing how long the sample holder is in its inverted position.
  14. 14. Cell avidity analysis apparatus (100) according to claim 13, wherein the one or multiple processors are further configured to, when executing the instructions, perform the operation of: once a predetermined period of time has lapsed while the sample holder (802) is in its inverted position, preferably while inside the casing (803), re-inverting the sample holder (802), preferably the entire cassette (801), in particular by means of the handling system (400), from said inverted position of the sample holder (802) back to the starting position of the sample holder (802), preferably wherein the one or multiple processors are further configured to, when executing the instructions, perform the operation of placing the sample holder (802), preferably the entire cassette (801), in the centrifuge unit (200) and centrifuging said sample holder (802).
  15. 15. Cell avidity analysis apparatus (100) according to any one claims 1-12, wherein the apparatus (100) comprises a non-transitory computer-readable medium with instructions encoded thereon, and one or multiple processors configured to, when executing the instructions, perform the operations of: 42 inverting the sample holder (802), in particular by means of the handling system (400), from a starting position, such as an upside up position, of the sample holder (802) into an inverted position, such as for example the upside down position, of the sample holder (802), preferably while the sample holder (802) is inside the casing (803); placing the sample holder (802), preferably while it (802) is inside the casing (803), into the centrifuge unit (200) in its inverted position, in particular by means of the handling system (400); centrifuging said sample holder (802), preferably while it (802) is inside the casing (803); reinverting the sample holder (802) into its starting position, in particular by means of the handling system (400), wherein said reinverting for example is performable within the centrifuge unit (802) and/or after, or at least partially simultaneously with, an optional step of removing the sample holder (802) from the centrifuge unit (802); and controlling and/or measuring the duration of centrifuging of the sample holder (802), and preferably also controlling and/or measuring at least one of: the time interval between the moment the sample holder (802) is inverted from its initial starting position to its inverted position and the moment it (802) is reinverted to its original position, such as the upside up position; and the time interval between the moment the sample holder (802) is inverted from its initial starting position to its inverted position and a later moment at which a further centrifuging starts after said sample holder (802) has been re-inverted to its original position, such as the upside up position, preferably wherein the one or multiple processors are further configured to, when executing the instructions, perform the operations of: placing the sample holder (802), preferably the entire cassette (801), unit (200) in its original position in the centrifuge; and further centrifuging said sample holder (802) after said sample holder (802) has been re-inverted to its original position.

Description

Title: Cell avidity analysis apparatus TECHNICAL FIELD The invention relates to a cell avidity analysis device. BACKGROUND In cell avidity analysis, which for instance may be performed to facilitate cell therapy drug development, the overall cellular binding strength, i.e. the cell avidity, is often analysed in vitro by applying a force to bound cells, e.g. effector cells bound to target cells. An in vitro cell avidity analysis may for example be performed in order to provide a relatively relevant prediction reflecting an in vivo interaction between effector cells, for instance T cells, and target cells, in particular target antigens or immune cells. It will be appreciated that analysing the cell avidity for different effector cells, which are provided with different candidate receptors, can allow one to compare different effector cells. Implementing cell avidity analysis at a relatively early stage of cell therapy drug development may thus facilitate relatively early identification of relatively good lead candidates, which thereby may accelerate the development process and/or make the development more time and/or cost effective. In cell avidity analysis processes, control over fluids and cells to be analysed and/or control over interaction and/or incubation time may be of high importance. For example, in order to obtain reproducible results, it may be important to tightly control incubation time and/or other parameters. Known methods for handling samples usually tend to require elaborate manipulation, in particular in manners requiring relatively much manual labour. Cell avidity analyses may predict cellular responses relatively well, and may drive relatively good and/or relatively well informed decisions at relatively early stages of drug selection and may improve clinical outcomes. And, although there are already processes and devices to perform cell avidity analysis, there still is a desire for devices and/or methods for further improving cell avidity analysis. It is an object of the present invention to provide a novel cell avidity analysis device, in particular one wherein samples can be analysed relatively precisely and/or wherein multiple, preferably relatively many, samples can be analysed simultaneously and/or in relative hight throughput format. SUMMARY OF THE INVENTION The present disclosure provides for a new and improved device for cell avidity analysis. In particular, the present invention provides for a cell avidity analysis apparatus according to claim 1 . In a first aspect, the cell avidity analysis apparatus comprises a housing for housing multiple components of the apparatus. The apparatus comprises a centrifuge unit located inside the housing, which may also be referred to as a so-called enclosure. Said centrifuge unit being arranged for holding and centrifuging a sample holder, preferably a sample holder held within a substantially hermetically sealed casing. The apparatus further comprises an imaging device, preferably a microscopy device, for imaging at least a first section of the sample holder, preferably said first section being formed by a section of a flow channel of said sample holder. Said imaging device is located inside the housing and outside the centrifuge unit. Further, the apparatus comprises a handling system located inside the housing. The handling system is arranged for placing the sample holder inside the centrifuge and/or arranged for taking the sample holder out of the centrifuge and bringing it towards the imaging device. For instance, the handling device may be arranged to place the sample holder on a first sample holder support for supporting the sample holder when the imaging device is imaging at least a first section of the sample holder. By providing an apparatus in which both a centrifuge unit and an imaging device is provided, as well as a handling device which can bring a sample holder from the centrifuge unit towards the imaging device and/or vice versa, a cell avidity analysis device can be provided which as a single device can be used for centrifugation and imaging, in particular microscopy. By allowing the handling system to place the sample holder in the centrifuge unit, it can be enabled that the centrifuge unit can start operating at the exact intended moment. As a result, samples may be analysed relatively precisely. Besides, samples may be analysed in relative high throughput format. By providing the imaging device outside of the centrifuge unit, the imaging device does not need to spin together with sample holder, which may make the apparatus less complex and/or relatively reliable/durable. It has-been found that imaging samples only after the centrifuging action has performed and the sample holder has already been removed from the centrifuge unit can provide for relatively good predictions reflecting an in vivo interaction between effector cells, for instance T cells, and target cells, in particular target antigens or immune cells. Surpris