Classifications

• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
  • G01N2035/00178—Special arrangements of analysers
  • G01N2035/00277—Special precautions to avoid contamination (e.g. enclosures, glove- boxes, sealed sample carriers, disposal of contaminated material)

Definitions

• the present invention relates to a system for performing chemical, biological and/or medical processes, preferably following respective protocols.
• the present invention aims at the provision of a system that prevents such contamination of containers by aerosols, vaporized substances or the like.
• the invention aims in particular at the provision of a compact, fully-enclosed system applicable as laboratory equipment.
• the present invention aims at the provision of a system that reduces or even fully prevents such contamination. It is thus an object of the present invention to provide a system for performing chemical, biological and/or medical processes which is capable of reducing such contamination in an effective and efficient manner, whereby the corresponding system components should be easy to control and non-complex.
• the system should preferably be a compact, fully-enclosed laboratory-size system.
• a system for performing chemical, biological and/or medical processes.
• processes can include analyses of specific substances or other reactions that may follow protocols such as chemical, biological and/or medical protocols.
• protocols such as chemical, biological and/or medical protocols.
• a chemical, biological or medical protocol is a sequence of steps performed e.g. during an analysis process or a reaction process.
• the system comprises holding means for holding a plurality of containers.
• the holding means can e.g. comprise holes or different means for receiving the containers or can be integrally formed with the containers.
• the containers are suitable for holding substances relevant for the process in question such as reagents or reaction products.
• the processes can thus be performed in these containers or recipients.
• reagents and/or reaction products can be inserted into and taken out from said containers using e.g. pipettes during the process as required e.g. by the respective protocol.
• typical reagents of interest may exemplarily be samples, buffers, solutions or the like.
• Suitable containers may be test tubes, vials, plates, flasks, channels, surfaces or the like.
• the holding means is configured and/or arranged such that the containers are arranged in at least two essentially parallel rows along a first direction when held by the holding means.
• a perfect parallelism may not be achieved such that the term essentially parallel is to be understood as parallel within the usual constructional tolerances.
• the holding means can comprise a suitable frame structure or the like to hold the containers or into which containers can be inserted.
• the containers can similarly be formed integrally with such frame structure.
• the containers are arranged in at least two (or more) rows along a first direction.
• said direction may be a direction of movement of the containers to a position for interaction with a pipette.
• a plurality of pipettes corresponding to a plurality of containers within one row or all rows may be provided to allow for simultaneous treatment of the containers.
• the holding means may be a frame structure adapted to hold a plurality of containers so that the containers form a grid (i.e. the containers being arranged in essentially parallel rows and essentially parallel columns).
• the system further comprises a gas outlet arranged to provide a gas flow along the first direction.
• the gas is air.
• suitable gases encompass nitrogen, argon and helium.
• a suitable gas outlet may be a simple hole, multiple, i.e. at least two holes, a matrix of holes and a suitable nozzle.
• the outlet may have an essentially circular shape or an elongated shape as desired.
• the gas outlet comprises a matrix of holes. Such matrix is advantageous as it can be adapted to the needs of the system and can in particular be used to extend the gas flow to a desired height as described below.
• the gas outlet comprises a matrix of circular holes, preferably with diameters between 1 mm and 3 mm, separated between 1 .5 mm and 3.5 mm measured from center to center.
• the gas outlet is adapted to provide a gas flow, in an area in between 1 cm to 10 cm in length times a length in between 1 cm to 15 cm.
• the gas outlet is preferably provided at a distance in between 1 cm and 5 cm before the openings of containers.
• the gas outlet is arranged to provide the gas flow along openings of containers of at least one of the at least two rows of containers.
• the gas outlet is arranged to provide the gas flow along openings of containers of a plurality of rows of containers. This may be achieved by providing the gas outlet comprising a matrix of holes.
• At least one flow barrier is arranged along the first direction and in between the at least two rows of containers for separating openings of one of the at least two rows of containers from openings of the other one of the at least two rows of containers.
• the flow barrier is adapted to prevent a flow or transfer of gas, aerosols, vaporized reagent, or the like from one of the at least two rows of containers to openings of the other one of the at least two rows of containers.
• the holding means is configured such that at least within each row, openings of the containers are arranged within a common plane along the first direction when held by the holding means, whereby the gas outlet is arranged to provide the gas flow along at least all of the openings within one row.
• part of the containers or all of the containers may be held by the holding member such that openings of the containers are held essentially in a common plane.
• Flow barriers are arranged in between pairs of rows of containers extending in parallel along the first direction and in a height direction perpendicular to the first direction and perpendicular to said common plane of the openings. Due to the arrangement of the at least one flow barrier in between the at least two rows of containers, the at least two rows of containers are mutually separated.
• the present invention further provides a method for performing chemical, biological and/or medical processes comprising holding a plurality of containers in at least two essentially parallel rows along a first direction.
• the method further comprises providing a gas flow along the first direction and at least along openings of containers of one of the at least two rows of containers.
• the method further comprises separating openings of one of the at least two rows of containers from openings of the other one of the at least two rows of containers using at least one flow barrier arranged along the first direction and in between the at least two rows of containers.
• Fig. 1 shows a three dimensional view of a system for performing chemical, biological and/or medical processes
• Fig. 2 shows a holding means for holding a plurality of containers
• Fig. 3 is a three dimensional illustration of holding means holding a plurality of containers, flow barriers and a gas flow along openings of containers of one row of containers;
• Fig. 4 shows a further holding means for holding a plurality of containers.
• FIG. 1 shows an example of a system 100 for performing chemical, biological and/or medical processes.
• the system 100 comprises a main housing 101 which covers internal components such as a controller (microprocessor) which is configured to control operations of the system components.
• a controller microprocessor
• the housing 101 of the system 101 encloses a partially open process space 103 within which the above discussed processes are performed.
• a pipette 105 is visible through an opening in a side wall of housing 101.
• the pipette is mounted to an arm 106 which is controlled by a controller (microprocessor) of the system.
• a door 107 is provided in a front wall of the housing 101 which can be opened by an operator to insert containers into the system for further processing.
• holding means 200 e.g. suitable frame structures, not visible in the figure
• a suitable algorithm can be provided for the controller such that using arm 106, chemical, biological and/or medical processes can be performed automatically following a suitable protocol e.g. implemented as software for the controller.
• the system comprises a means 106, 105, preferably at least one pipette 105, for adding or removing a substance to or from at least one of the plurality of containers.
• the system further comprises a controller configured for automatically controlling said means, preferably said pipette.
• Fig. 2 shows a frame 201 as an exemplary part of holding means 200. Inserted into the system 100, such frame extends along the first direction 601 (see also Fig. 3 below) and includes a plurality of essentially circularly shaped recesses 203 or holes 203, each recess 203 for receiving a container 300. Alternatively, the containers 300 may be formed integrally with the frame 201.
• the containers 300 shown in Fig. 2 (the frame 201 exemplarily holds eight containers 300 of which only one is indicated with a reference numeral) thus are a plurality of containers being arranged in a row along a first direction being held by a part of the holding means.
• the holding means 200 comprises at least two frames 201 which extend along the first direction 601 , the frames 201 being removably insertable into the main housing 101 of the system 100, each frame 201 having a plurality of essentially circularly shaped recesses 203, each recess 203 being for holding a respective container 300 of the plurality of containers 300.
• openings 301 of the containers 300 are arranged within a common plane along the first direction 601 , whereby in the shown example said common plane is essentially a plane also including the recesses 203 of the frame 201.
• said common plane is essentially a plane also including the recesses 203 of the frame 201.
• an opening 301 of a respective container 300 of the plurality of containers 300 is arranged essentially at a same height 603 (see Fig. 3 below) as the essentially circularly shaped recess 301 when the respective container 300 is held by the corresponding frame.
• the frame can be provided with a two-dimensional code, e.g. a QR-code, at a suitable position such as e.g. on a top surface at the left end of the frame 201 in Fig. 2.
• the frame 201 is provided with a two-dimensional code, preferably with a QR (Quick Response) - code, for identifying substances per container or processes performed in each container 300 held by the frame 201 .
• the system 100 preferably comprises means for reading said two-dimensional code, when the frame 201 is inserted in the system and the controller is configured to automatically perform a process in accordance with information stored in the two-dimensional code.
• the frame may hold one or more different containers or recipients 313 which may be used for holding further substances as desired.
• Fig. 3 schematically illustrates holding means 200 holding a plurality of containers 300.
• the holding means 200 are configured such that the plurality of containers 300 is arranged in at least two essentially parallel rows along the first direction 601 when held by the holding means 200.
• the first two rows parallel to the direction 601 visible in the figure are indicated by reference numerals 350 and 360.
• the holding means 200 may for example be realized by multiple (in the example shown in Fig. 3 three) frames 201 as shown in Fig. 2.
• the holding means 200 may also be realized as a holder for holding a grid of containers 300 so that rows of containers along the first direction 601 are formed as illustrated.
• the system further comprises a gas outlet (not shown) arranged to provide a gas flow (illustrated by arrows forming groups 501 , 503) along the first direction 601 and at least along openings of containers of one of the at least two rows of containers.
• the gas flow is along the openings of containers of row 350.
• the gas flow may be restricted to a single row such as said row 350 but may also be along more than one or all of the rows.
• two flow barriers 400 in the shown example wall-shaped members 400, are arranged along the first direction 601 and in between at least two rows of containers 300 for separating openings 301 of one of the at least two rows of containers from openings 301 of the other one of the at least two rows of containers.
• a first flow barrier 400 is provided between row 350 and row 360 to prevent a transfer of gas, gaseous substances, aerosols and the like, between openings 301 of containers 300 e.g. of row 350 to openings 301 of containers 300 of row 360, and vice versa.
• the at least one flow barrier 400 extends along the first direction 601 from a first position 801 before the containers along the first direction 601 until a second position 803 behind the containers 300 along the first direction 601 so as to be positioned between all of the containers 300 of the at least two rows 350, 360 of containers 300.
• each flow barrier extends along the first direction and along a second direction 603, i.e. a height direction.
• the at least one flow barrier is essentially wall-shaped and the height of the at least one flow barrier is measured in a direction essentially perpendicular to said common plane.
• the at least one flow barrier 400 has an essentially uniform height along its length which is in between 0,5 cm and 10 cm, preferably in between 0,8 cm and 9 cm, more preferably in between 0,9 cm and 8 cm and most preferably in between 1 cm and 7 cm.
• a length of the at least one flow barrier in the first direction is in between 0,5 cm and 50 cm, preferably in between 0,8 cm and 40 cm, more preferably in between 1 cm and 30 cm, and most preferably in between 1 cm and 20 cm.
• two flow barriers 400 are exemplarily provided to separate containers or rows of containers.
• the horizontal flow goes from a gas outlet (not shown) which is arranged at a distance ahead of the barriers. It turned out that a distance between the gas outlet and the flow barriers should not be too small so that a uniform non-turbulent fully developed gas flow is applied.
• a distance between the at least one flow barrier and the gas outlet is not less than 1 cm, preferably not less than 2 cm, more preferably not less than 3 cm, even more preferably not less than 4 cm, and most preferably not less than 5 cm. It turned out that keeping such distance supports a desirable flow development helping to prevent turbulences. Turbulences are undesirable as they may promote exchange e.g. of aerosols over the flow barriers.
• the system comprises at least three, preferably a plurality of rows of containers and at least two, preferably a plurality of flow barriers arranged respectively between pairs of rows of containers, whereby the gas outlet is arranged such that the gas-flow comprises a first portion which flows along at least all of the openings of the containers within each row in between the flow barriers and a second portion which flows above the flow barriers.
• part of the gas flow (a first portion) is channelled by said barriers, i.e. flows in between the two barriers, and a part (a second portion) flows on top of or over the barriers at a higher speed.
• the velocity difference is due to the fluidic resistance caused by the aspect ratio (height/separation) of the space between the barriers.
• the gas or air flow is extracted downwards or, alternatively, upwards, lateral, diagonal or in the direction of the flow.
• the system 100 comprises at least two flow barriers 400 and a negative pressure source 700, preferably a pump 700, for creating a pressure difference between the negative pressure source 700 and the gas outlet such that gas provided by the gas outlet moves towards the negative pressure source 700.
• a negative pressure source 700 preferably a pump 700
• the negative pressure source 700 it becomes possible to generate a directed gas flow (preferably air flow) from the gas outlet towards the negative pressure source.
• This configuration turned out to be advantageous as by directing the gas flow in this way, turbulences which otherwise could promote undesirable exchange e.g. of aerosols between rows can be efficiently prevented with a simple non-complex construction.
• the gas outlet is arranged to provide the gas flow to flow along an initial flow direction (e.g. along the first direction 601 ), whereby after having passed at least the openings of all of the containers of one row 350, the gas flow is directed in a predetermined direction different from an initial direction, e.g. downwards as shown in Fig. 3.
• the system 100 further comprises a controller for controlling the negative pressure source 700 such that a gas flow rate in between the at least two flow barriers is in between 100 and 200 cm 3 /s, preferably in between 120 and 180 cm 3 /s, more preferably in between 140 and 170 cm 3 /s, and most preferably in between 160 and 170 cm 3 /s.
• the system is scalable, i.e. can comprise a larger number of rows of containers whereby these values are essentially constant per row, essentially independently of the number of rows, i.e. the size of the system.
• the values of the flow rate are such that the gas speed in between the gas outlet and the at least one flow barrier is in between 0.3 m/s and 0.5 m/s. It turned out that above this value, the flow was no longer laminar but started to be turbulent. Furthermore, high speeds over the openings 301 of the tubes 300 can cause the pressure to drop locally, thus promoting evaporation. This can occur in high pressure systems such as jets of air
• the negative pressure source is a pump configured to pump gas at a flow rate which per row of containers is not lower than that of the gas outlet.
• a preferably low-pressure gas flow is locally conducted along a series of flow barriers, placed parallel to the direction of the gas flow, i.e. along the first direction.
• the airflow is preferably extracted by a negative pressure source, which causes the flow to be directed (upwards, downwards, lateral, diagonal or along its initial).
• this solution ensures that turbulence will not cause accidental transport of aerosols or other elements (such as small particles) into containers of adjacent rows.
• Alternative solutions, like high-pressure jets are more expensive and complex (e.g.
• the use of parallel flow barriers ensures a desirable flow development and more predictable air conditions.
• the barriers avoid lateral transfer of aerosols.
• the relationship between the width and the height of the barriers can be chosen such that the airflow is stronger on top of the barriers than along the barriers.
• two simultaneous phenomena may develop.
• the aforementioned localized unidirectional transport of aerosols parallel to the barriers is possible.
• a higher speed gas or air lid develops on top of the barriers, which further avoids aerosol transfer across barriers. It turned out that this solution is ideal for manipulation of the containers with liquid handling devices, robots, pipettes or fluid manipulation tools that may be introduced and removed from the tubes.
• the gas flow speed can be kept also low, it is possible to extract this gas or air at a short length after the barriers with low turbulence and in any direction, by means of a negative pressure source.
• This source re-directs the flow towards itself, prevents aerosol spreading mechanisms, such as impingement and minimizes circulation to avoid build-up of contamination reservoirs.
• the negative source and the gas outlet may be part of the same gas/air circulation system, which helps equilibrate the positive and negative pressures required to direct the gas flow and to extract it.
• a filter is provided (e.g. HEPA or other) in the circulation system that removes the aerosols continuously and helps improve gas quality inside the device.
• Fig. 4 shows a holding means 200 comprising a further embodiment of a frame 201 '. Inserted into the system 100, such frame extends along the first direction 601 (see also Fig. 3 below) and is adapted to hold at least two rows, in the shown example three rows 350, 360, 370 of containers 300.
• Flow barriers 400 are arranged in between the rows 350, 360, 370 of containers.
• the flow barriers are arranged to channel or guide a gas flow (not shown) at least along the holes 203 for removing gaseous substances, aerosols or the like.
• the flow barriers may be separate members attached to the frame 201 ' or may be an integral part of a structure including also frame 201 '.
• the containers may be removably inserted into corresponding holes of the frame 201 ' but may also be integrally formed with the frame 201 '.
• Fig. 4 shows further containers 313, one further container 313 being arranged per row 350, 360, 370 of containers. Such further containers 313 may be used for holding a different reagent as containers 300.
• further flow barriers 401 are provided in between the further containers 313 fulfilling the same purpose as the flow barriers 400 which are arranged in between the rows 350, 360, 370 of containers 300.
• the system may be characterized by: -
• the gas outlet is located 3 cm ahead of the flow barriers 400, with an outlet airspeed of 0,5m/s and a flowrate of 165 cm 3 /s per space between barriers.
• the height of the barriers 400 is 3 cm over the plane formed by the openings 301 of the containers 300 and the separation between the barriers 400 is 1 cm.
• the containers 300 are placed in rows in the separation space between barriers 400.
• the length of the barriers 400 is 12 cm
• the negative pressure source has a cross section of 6 cm x 12 cm, starting 1 cm after the length of the barriers 803.
• the outlet airspeed is 0.5m/s and the flowrate is 165cm3/s per space between barriers 400.

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• Physics & Mathematics (AREA)
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• Life Sciences & Earth Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Analytical Chemistry (AREA)
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• General Health & Medical Sciences (AREA)
• General Physics & Mathematics (AREA)
• Immunology (AREA)
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• Apparatus Associated With Microorganisms And Enzymes (AREA)
• Feeding, Discharge, Calcimining, Fusing, And Gas-Generation Devices (AREA)

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Citations (5)

• 2017
  • 2017-11-13 DE DE112017005675.6T patent/DE112017005675T5/de active Pending
  • 2017-11-13 WO PCT/EP2017/079086 patent/WO2018087372A1/en active Application Filing
  • 2017-11-13 ES ES201990036A patent/ES2715518B2/es active Active

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