# US 7,608,222 B2 · Assembly and method for performing parallel chemical experiments, in particular crystallisation experiments

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- Number: US 7,608,222 B2
- Document ID: US7608222B2
- Status: Granted
- Kind: B2
- Application number: 10/523,732
- Filed: 2003-08-02
- Published: 2006-07-13
- Granted: 2009-10-27
- Earliest claimed: 2003-08-02
- Assignees: Avantium International B.V.
- Inventors: Erwin Blomsma; Adriaan Jan van Langevelde; Danny Dirk Peter Willem Stam
- Web page: https://patentgrep.com/patent/US7608222B2

## CPC

- B01J 19/0046: {Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays (synthesis methods per se C40B50/00)}
- B01D 9/0031: {by heating (B01D9/0022, B01D9/0027 take precedence)}
- B01D 9/0072: {Crystallisation in microfluidic devices}
- B01D 9/0077: {Screening for crystallisation conditions or for crystal forms}
- B01L 3/06: Crystallising dishes
- B01L 3/50255: {Multi-well filtration}
- B01L 3/5085: {for multiple samples, e.g. microtitration plates}
- B01J 2219/00286: Reactor vessels with top and bottom openings
- B01J 2219/00308: interchangeably mounted in racks or blocks
- B01J 2219/00333: Closures attached to the reactor vessels
- B01J 2219/00335: Septa
- B01J 2219/00373: Hollow needles
- B01J 2219/00376: in multiple or parallel arrangements
- B01J 2219/00423: using filtration, e.g. through porous frits
- B01J 2219/00495: Means for heating or cooling the reaction vessels
- B01J 2219/00585: Parallel processes
- B01J 2219/00599: Solution-phase processes
- B01J 2219/00756: Compositions, e.g. coatings, crystals, formulations
- B01L 7/52: {with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples}
- B01L 2200/026: Fluid interfacing between devices or objects, e.g. connectors, inlet details
- B01L 2200/0684: Venting, avoiding backpressure, avoid gas bubbles
- B01L 2300/044: pierceable, e.g. films, membranes
- B01L 2300/0681: Filter
- B01L 2300/0829: Multi-well plates; Microtitration plates
- B01L 2300/10: Means to control humidity and/or other gases
- B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01D: SEPARATION (separating solids from solids by wet methods B03B, B03D; by pneumatic jigs or tables B03B; by other dry methods B07; magnetic or electrostatic separation of solid materials from solid materials or fluids, separation by high-voltage electric fields B03C; centrifuges, vortex apparatus B04; presses per se for squeezing-out liquid from liquid-containing material B30B9/02; treatment of water C02F, e.g. softening by ion-exchange C02F1/42; {arrangements of air intake cleaners in gas turbine plants F02C7/05} ; arrangements or mounting of filters in air-conditioning, air-humidification or ventilation F24F13/28)
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE

## Abstract

An assembly and method for performing parallel chemical experiments, in particular crystallisation experiments. The assembly has a main body having a first and a second face on opposite sides thereof. Multiple bores extend through said main body between said first and second face. Tubular liners are provided having openings at opposite ends thereof, each liner removably fitting in a bore in the main body. First closure means close the openings of the liners at the first face of the main body. Second closure means close the openings of the liners at the second face of the main body. The first and second closure means are fastenable to said main body, so that an experimentation chamber is defined within each liner.

## Claims

### Claim 1

An assembly for performing parallel chemical experiments, said assembly comprising:
a main body having a first and a second face on opposite sides thereof, multiple bores extending through said main body between said first and second face,
liners each having an opening at the first face of the main, each liner removably fitting in a bore in the main body, the liners are each provided at the first face of the main body with at least one outwardly directed support projection, and the bores in the main body are each provided with a corresponding recess for receiving the support projection, and
first closure means for closing the openings of the liners at the first face of the main body, which first closure means comprise one or more elastic first sealing members and a first cover plate, so that said first sealing members are interpositioned between the ends of the liners and the first cover plate,
said first closure plate being fastenable to said main body, so that a closed experimentation chamber is defined within each liner,
wherein the liners are tubular liners, each liner also having openings at opposite ends thereof, and wherein second closure means are provided for closing the openings of the liners at the second face of the main body, said second closure means comprising one or more second elastic sealing members and a second cover plate which is fastenable to the main body, so that said second sealing members are interpositioned between the ends of the tubular liners and the second cover plate.

### Claim 2 (depends on 1)

Assembly according to claim 1, wherein said first closure means comprise multiple first sealing members, each first sealing member engaging an end face of a liner.

### Claim 3 (depends on 2)

Assembly according to claim 2, wherein at least one of the first face of the main body and the first cover plate is provided with recesses at the locations of the liner ends for receiving a first sealing member.

### Claim 4 (depends on 1)

Assembly according to claim 1, wherein said second closure means comprise multiple sealing members, each second sealing member engaging an end face of a liner.

### Claim 5 (depends on 4)

Assembly according to claim 4, wherein at least one of the second face of the main body and the second cover plate is provided with recesses at the locations of the liner ends for receiving a second sealing member.

### Claim 6 (depends on 1)

Assembly according to claim 1, wherein at least one of the first and the second cover plate is provided with bores extending in line with the bores of the main body, and wherein at least one of the first and second sealing members are pierceable.

### Claim 7

A method for performing parallel chemical experiments, wherein use is made of a system comprising:
an assembly for performing parallel chemical experiments, said assembly comprising:
a main body having a first and a second face on opposite sides thereof, multiple bores extending through said main body between said first and second face,
tubular liners having openings at opposite ends thereof, each liner removably fitting in a bore in the main body, the liners are each provided at the first face of the main body with at least one outwardly directed support projection, and the bores in the main body are provided with a corresponding recess for receiving the support projection, and
first closure means for closing the openings of the liners at the first face of the main body, which first closure means comprise one or more elastic first sealing members and a first cover plate, so that said first sealing members are interpositioned between the ends of the liners and the firs cover plate,
second closure means for closing the openings of the liners at the second face of the main body, and said second closure means comprising one or more second elastic sealing members and a second cover plate which is fastenable to the main body, so that said second sealing members are interpositioned between the ends of the tubular liners and the second cover plate,
said first and second closure means being fastenable to said main body, so that an experimentation chamber is defined within each liner, and
a filtration device having channels with inlets corresponding to the bores in the main body of the experimentation assembly and a filter in each channel, which method comprises the steps of:
removing of the top cover plate of the experimentation assembly when in horizontal position and of the associated at least one sealing member,
bringing said filtration device against the top face of the main body, and
subsequently reversing said system such that the contents of the experimentation chambers enters said channels in the filtration device and is filtered.

### Claim 8 (depends on 7)

A method according to claim 7, wherein said channels in said filtration device have outlets and wherein said system further comprises a collecting device having collecting chambers with inlets corresponding to the outlets of the filtration device, such that the filtered contents of the experimentation chambers enters said collecting chambers.

### Claim 9 (depends on 7)

A method according to claim 7, wherein the parallel chemical experiments are crystallisation experiments and crystallisation is effected in the experimentation chambers.

### Claim 10 (depends on 7)

A method according to claim 7, wherein the parallel chemical experiments include solid form screening of molecules.

### Claim 11 (depends on 10)

A method according to claim 10, wherein the solid form screening of molecules is for active pharmaceutical ingredients.

### Claim 12 (depends on 10)

A method according to claim 10, wherein the solid form screening of molecules is selected from the group consisting of salt screening, polymorph screening, and enantiomer separation screening.

### Claim 13 (depends on 1)

Assembly according to claim 1, wherein the parallel chemical experiments are crystallisation experiments.

### Claim 14 (depends on 7)

A method according to claim 7, wherein:
the main body of said assembly for performing parallel chemical experiments is a solid body of a heat conducting material, and
at least one of the first and second closure means comprise sealing members which are pierceable, and
said method further comprising the steps of:
heating the content in the experimentation chambers using heating means, wherein said heating means are mounted in contact with at least one of said main body and cover plate, thereby creating a vapor in at least one of the experimentation chambers, and
discharging said vapor from the system using a vapor discharge assembly, said vapor discharge assembly comprising multiple hollow needle members, each adapted to be pierced through a sealing member so that vapor discharges via said hollow needle members.

### Claim 15 (depends on 14)

A method according to claim 14, wherein said needle members are upwardly directed and arranged to pierce through the sealing members sealing the bottom face of the experimentation assembly in horizontal orientation.

### Claim 16 (depends on 14)

A method according to claim 14, wherein the system that is used further comprises a feed assembly for feeding a substance into the experimentation chambers, said feed assembly comprising at least one hollow needle member adapted to be pierced through a sealing member.

### Claim 17

An assembly for performing parallel chemical experiments, said assembly comprising:
a main body having a first and a second face on opposite sides thereof, multiple bores extending through said main body between said first and second face,
liners each having an opening at the first face of the main body, each liner removably fitting in a bore in the main body, the liners are each provided at the first face of the main body with at least one outwardly directed support projection, and the bores in the main body are provided with a corresponding recess for receiving the support projection, and
first closure means for closing the openings of the liners at the first face of the main body, which first closure means comprise one or more elastic first sealing members and a first cover plate, so that said first sealing members are interpositioned between the ends of the liners and the first cover plate,
said first closure plate being fastenable to said main body, so that a closed experimentation chamber is defined within each liner,
wherein the liners are tubular liners, each liner also having openings at opposite ends thereof, and wherein second closure means are provided for closing the openings of the liners at the second face of the main body, said second closure means comprising one or more second elastic sealing members and a second cover plate which is fastenable to the main body, so that said second sealing members are interpositioned between the ends of the tubular liners and the second cover plate, and
a filtration device, separate from the main body, said filtration device comprising a plate having multiple channels, with inlets corresponding to the bores in the main body of the experimentation assembly and a filter in each channel.

### Claim 18 (depends on 17)

Assembly according to claim 17, wherein the parallel chemical experiments are crystallisation experiments.
