Chemical treatment station for use with cassette having individually addressable sample mini-columns

• US 6,168,760 B1
• Filed: 02/25/1999
• Issued: 01/02/2001
• Est. Priority Date: 07/09/1996
• Status: Expired due to Fees

• Current Assignee: Amersham Pharmacia Biotech AB
• Original Assignee: Amersham Pharmacia Biotech AB
• Inventors: Horn, Marcus J.
• Primary Examiner(s): Noland, Thomas P.
• Application Number:
  US09/258,009
• Time in Patent Office: 677 Days
• Field of Search: 422/67, 422/63, 422/70, 422/101, 422/102, 436/54, 734/55, 141/130
• US Class Current: 422/67
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• CPC Class Codes: B01L 3/50255 Multi-well filtration
• CPC Class Codes: B01L 3/50855 using modular assemblies of strips or of individual wells
• CPC Class Codes: B01L 9/06 Test-tube stands; Test-tube holders
• CPC Class Codes: G01N 2030/027 Liquid chromatography
• CPC Class Codes: G01N 2030/8804 automated systems
• CPC Class Codes: G01N 2030/8831 involving peptides or proteins
• CPC Class Codes: G01N 2030/8881 Modular construction, specially adapted therefor
• CPC Class Codes: G01N 2035/00752 bar codes
• CPC Class Codes: G01N 30/24 Automatic injection systems
• CPC Class Codes: G01N 30/36 in high pressure liquid systems
• CPC Class Codes: G01N 30/466 with separation columns in parallel
• CPC Class Codes: G01N 30/6043 in parallel
• CPC Class Codes: G01N 30/88 Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
• CPC Class Codes: G01N 35/00732 Identification of carriers, materials or components in automatic analysers
• CPC Class Codes: Y10T 436/119163 with aspirator of claimed structure

Abstract

This invention is directed to a cassette chemical chemical treatment station. The system with the cassette performs various complex chemistries with minimal human intervention, near-zero dead volume, and flow-through protocols pursuant to a predetermined instruction set encoded on a multiple-address chemical treatment cassette assembly. The cassette assembly having a high pressure interface capability to permit direct insertion of the mini-column into a high-pressre solvent line for use as a support column for HPLC analysis. A sample loader loads analyte samples either singly or simultaneously into the multiple, addressable mini-columns without the need to load the sample funnel/column assembly into a separate reaction chamber. The inventive system reads the machine readable instruction code and performs chemistries on the analyte, including mixing solvents, reactants and buffers; detaching and shuttling the analyte back and forth performing complex chemistries either on or off-column; salvation of powdered or lyophillized reagents; and performing in-line, on-board analysis. These protocols are performed automatically pursuant to instructions contained on a bar code, without having to remove the cassette or interface from the CTS, or otherwise require human intervention. The same chemistries may be performed on all sample mini-column addresses, or a separate completely independent set of protocols may be defined for each address, or for each block of addresses pursuant to the instructions contained in the machine readable code on the cassette.

Claims

1. A chemical treatment station for performing predetermined chemistries on a plurality of preselected retained chemical samples located in a chemical treatment cassette having a plurality of individually addressable sample mini-columns for retaining preselected chemical samples, the mini-columns having tapered inlet ports and outlet ports, said chemical treatment station comprising:

a) a code reader for reading a machine readable code disposed on the chemical treatment cassette to identify the predetermined specific chemistry protocols to be performed on the retained chemical samples;

b) a scanner to identify mini-column addresses wherein said central chamber of said mini-column is populated;

c) a micro-controller interface for communicating from said code reader to a micro-controller said identified specific chemistry protocols, said micro-controller accessing specific process algorithms pursuant to the specific identified chemistry protocols, said process algorithms defining and communicating to said micro-controller interface step-wise micro-controller control instructions to enable execution of said identified specific chemistries at said populated mini-column addresses;

d) a cassette/treatment station interface for enabling near-zero dead volume flow-through communication of the chemical treatment cassette with said chemical treatment station, said cassette/treatment station interface comprising;

i) a cassette interface dock for precision alignment of the chemical treatment cassette,

ii) a first nozzle array comprising a plurality of nozzles spatially arrayed to be congruous with mini-column inlet ports and reagent well inlet ports for flow-through localized interfacing with the mini-column inlet ports and the reagent well inlet ports,

iii) a second nozzle array having a plurality of nozzles spatially arrayed to be congruous with the mini-column outlet ports and reagent well outlet ports for flow through communication with the mini-column outlet ports and the reagent well outlet ports,

iv) said first nozzle array positioned above said cassette interface dock, said nozzles in said first array having nozzles tips extending downward towards said cassette interface dock,

v) said second nozzle array position below said cassette interface dock, said nozzles in said second nozzle array having nozzle tips extending upwards to said cassette interface dock, and

vi) said nozzles in said first array and said nozzles in said second array establishing a flow-through localized interface by first aligning said chemical treatment cassette in said cassette interface dock and by fitting said nozzle tips in said first nozzle array against said tapered opening of said mini-column inlet ports, and by fitting said nozzle tips in said second nozzle array against said tapered opening of said mini-column outlet ports; and

e) a chemical delivery subsystem for providing automatic flow through chemistries on the preselected chemical samples further comprising;

i) a solvent bank for providing a plurality of reagents and solvents for solubilizing said reagents retained therein and for reaction with the preselected chemical samples pursuant to said identified predetermined specific chemistry protocols,

ii) a rotary valve array further comprising a mini-column inlet port rotary valve array for individual addressing of mini-column inlet ports, a mini-column outlet port rotary valve array for individual addressing of mini-column outlet ports, said mini-column inlet port rotary valve array and said mini-column outlet port rotary valve array being synchronized to a single mini-column address to permit active, flow-through localized interface with only one mini-column at a time, and a reagent well inlet port rotary valve array for individual addressing of reagent well inlet ports, a reagent well outlet port rotary valve array for individual addressing of reagent well outlet ports, said reagent well inlet port rotary valve array and said reagent well outlet port rotary valve array being synchronized to a single reagent well address to permit active, flow-through localized interface with only one reagent well at a time,

iii) a plurality of accumulators for temporary storage of solvents and reagents, and temporary storage of detached chemical sample to enable chemistries to be performed on said detached samples, and to enable collateral chemistries not including said detached samples as a reagent to be performed in the mini-columns,

iv) a mixer/diluter reservoir in communication with said solvent bank, reagent wells, and mini-columns for temporary retention of at least one of a solvent, reagent, sample, and mixtures thereof, and

v) a pneumatic pressurizing system for bi-directional transfer of solvents, reagents, and chemical samples to and from said reagent wells, said mini-columns, said accumulators, and said mixer/diluter, and for supplying inert gas to said chemical treatment delivery subsystem.

2. A chemical treatment station as in claim 1 wherein said analyzer subsystem is a high performance liquid chromatograph.

3. The chemical treatment station according to claim 2 comprising:

the mini-columns having a plurality of reagent wells for retaining reagents, the reagent wells having tapered inlet ports and outlet ports;

said nozzles in said first array and said nozzles in said second array establishing a flow-through localized interface by further fitting said nozzle tips in said first nozzle array against said reagent well inlet ports;

the solvent bank for providing a plurality of reagents and solvents to said reagent wells for solubilizing said reagents retained therein; and

the chemical delivery subsystem for providing automatic flow through chemistries on the preselected chemical samples further comprising a valve for integration of an analyzer subsystem into said chemical delivery subsystem to permit automatic analysis of the sample retained in said mini-columns without removal of said mini-columns from said chemical treatment cassette and without disengaging said cassette/treatment station interface.

4. A chemical treatment station for performing predetermined chemistries on a plurality of preselected retained chemical samples located in a chemical treatment cassette having a plurality of individually addressable sample mini-columns for retaining preselected chemical samples, the mini-columns having tapered inlet ports and outlet ports, and capable of accepting a plurality of reagent wells for retaining reagents, the reagent wells having tapered inlet ports and outlet ports, said chemical treatment station comprising:

a) a code reader for reading a machine readable code disposed on the chemical treatment cassette to identify the predetermined specific chemistry protocols to be performed on the retained chemical samples;

b) a scanner to identify mini-column addresses wherein said central chamber of said mini-column is populated;

c) a micro-controller interface for communicating from said code reader to a micro-controller said identified specific chemistry protocols, said micro-controller accessing specific process algorithms pursuant to the specific identified chemistry protocols, said process algorithms defining and communicating to said micro-controller interface step-wise micro-controller control instructions to enable execution of said identified specific chemistries at said populated mini-column addresses;

d) a cassette/treatment station interface for enabling near-zero dead volume flow-through communication of the chemical treatment cassette with said chemical treatment station, said cassette/treatment station interface comprising;

i) a cassette interface dock for precision alignment of the chemical treatment cassette,

ii) a first nozzle array comprising a plurality of nozzles spatially arrayed to be congruous with mini-column inlet ports and reagent well inlet ports for flow-through localized interfacing with the mini-column inlet ports and the reagent well inlet ports,

iii) a second nozzle array having a plurality of nozzles spatially arrayed to be congruous with the mini-column outlet ports and reagent well outlet ports for flow through communication with the mini-column outlet ports and the reagent well outlet ports,

iv) said first nozzle array positioned above said cassette interface dock, said nozzles in said first array having nozzles tips extending downward towards said cassette interface dock,

v) said second nozzle array position below said cassette interface dock, said nozzles in said second nozzle array having nozzle tips extending upwards to said cassette interface dock, and

vi) said nozzles in said first array and said nozzles in said second array establishing a flow-through localized interface by first aligning said chemical treatment cassette in said cassette interface dock and by compression fitting said nozzle tips in said first nozzle array against said tapered opening of said mini-column inlet ports and said reagent well inlet ports, and by compression fitting said nozzle tips in said second nozzle array against said tapered opening of said mini-column outlet ports and said reagent well outlet ports; and

e) a chemical delivery subsystem for providing automatic flow through chemistries on the preselected chemical samples further comprising;

i) a solvent bank for providing a plurality of reagents and solvents to said reagent wells for solubilizing said reagents retained therein and for reaction with the preselected chemical samples pursuant to said identified pre-determined specific chemistry protocols,

ii) a valve array further comprising a mini-column inlet port valve array for individual addressing of mini-column inlet ports, a mini-column outlet port valve array for individual addressing of mini-column outlet ports, said mini-column inlet port valve array and said mini-column outlet port valve array being synchronized to a single mini-column address to permit active, flow-through localized interface with only one mini-column at a time, and a reagent well inlet port valve array for individual addressing of reagent well inlet ports, a reagent well outlet port valve array for individual addressing of reagent well outlet ports, said reagent well inlet port valve array and said reagent well outlet port valve array being synchronized to a single reagent well address to permit active, flow-through localized interface with only one reagent well at a time,

iii) a plurality of accumulators for temporary storage of solvents and reagents, and temporary storage of detached chemical sample to enable chemistries to be performed on said detached samples, and to enable collateral chemistries not including said detached samples as a reagent to be performed in the mini-columns,

iv) a mixer/diluter reservoir in communication with said solvent bank, reagent wells, and mini-columns for temporary retention of at least one of a solvent, reagent, sample, and mixtures thereof,

v) a pneumatic pressurizing system for bi-directional transfer of solvents, reagents, and chemical samples to and from said reagent wells, said minicolumns, said accumulators, and said mixer/diluter, and for supplying inert gas to said chemical treatment delivery subsystem, and

vi) a valve for integration of an analyzer subsystem into said chemical delivery subsystem to permit automatic analysis of the sample retained in said mini-columns without removal of said mini-columns from said chemical treatment cassette and without disengaging said cassette/treatment station interface.

5. A chemical treatment station as in claim 4 wherein said analyzer subsystem is a high performance liquid chromatograph.

6. A high performance liquid chromatograph for performing predetermined liquid chromatography tests on a plurality of preselected retained chemical samples located in a chemical treatment cassette having a plurality of individually addressable sample mini-columns for retaining preselected chemical samples, the minicolumns having tapered inlet ports and outlet ports, said chemical treatment station comprising:

a) a code reader for reading a machine readable code disposed on the chemical treatment cassette to identify the predetermined specific chemistry protocols to be performed on the retained chemical samples;

b) a scanner to identify mini-column addresses wherein said central chamber of said mini-column is populated;

c) a micro-controller interface for communicating from said code reader to a micro-controller said identified specific chemistry protocols, said micro-controller accessing specific process algorithms pursuant to the specific identified chemistry protocols, said process algorithms defining and communicating to said micro-controller interface step-wise micro-controller control instructions to enable execution of said identified specific chemistries at said populated mini-column addresses;

d) a cassette/treatment station interface for enabling near-zero dead volume flow-through communication of the chemical treatment cassette with said chemical treatment station, said cassette/treatment station interface comprising;

i) a cassette interface dock for precision alignment of the chemical treatment cassette,

ii) a first nozzle array comprising a plurality of nozzles spatially arrayed to be congruous with mini-column inlet ports and reagent well inlet ports for flow-through localized interfacing with the mini-column inlet ports and the reagent well inlet ports,

iii) a second nozzle array having a plurality of nozzles spatially arrayed to be congruous with the mini-column outlet ports and reagent well outlet ports for flow through communication with the mini-column outlet ports and the reagent well outlet ports,

iv) said first nozzle array positioned above said cassette interface dock, said nozzles in said first array having nozzles tips extending downward towards said cassette interface dock,

v) said second nozzle array position below said cassette interface dock, said nozzles in said second nozzle array having nozzle tips extending upwards to said cassette interface dock, and

vi) said nozzles in said first array and said nozzles in said second array establishing a flow-through localized interface by first aligning said chemical treatment cassette in said cassette interface dock and by aligning said nozzle tips in said first nozzle array against said tapered opening of said mini-column inlet ports; and

e) a chemical delivery subsystem for providing automatic flow through chemistries on the preselected chemical samples further comprising;

i) a solvent bank for providing a plurality of reagents and solvents for solubilizing said reagents retained therein and for reaction with the preselected chemical samples pursuant to said identified pre-determined specific chemistry protocols,

ii) a valve array for individual addressing of mini-column inlet ports, individual addressing of mini-column outlet ports, individual addressing of reagent well inlet ports, and individual addressing of reagent well outlet ports, said valve array being synchronized to a single mini-column address to permit active, flow-through localized interface with only one mini-column at a time and to permit active, flow-through localized interface with only one reagent well at a time,

iii) a plurality of accumulators for temporary storage of solvents and reagents, and temporary storage of detached chemical sample to enable chemistries to be performed on said detached samples, and to enable collateral chemistries not including said detached samples as a reagent to be performed in the mini-columns,

iv) a mixer/diluter reservoir in communication with said solvent bank, reagent wells, and mini-columns for temporary retention of at least one of a solvent, reagent, sample, and mixtures thereof, and

v) a pneumatic pressurizing system for bi-directional transfer of solvents, reagents, and chemical samples to and from said reagent wells, said minicolumns, said accumulators, and said mixer/diluter, and for supplying inert gas to said chemical treatment delivery subsystem.