Solid phase system for sequential reactions

• US 5,437,979 A
• Filed: 08/24/1992
• Issued: 08/01/1995
• Est. Priority Date: 07/24/1989
• Status: Expired due to Term

• Current Assignee: Beckman Instruments, Inc. (Danaher Corporation)
• Original Assignee: Beckman Instruments, Inc. (Danaher Corporation)
• Inventors: Rampal, Jang B., Harbaugh, Jon F.
• Primary Examiner(s): Fleisher, Mindy B.
• Application Number:
  US07/934,286
• Time in Patent Office: 1,072 Days
• Field of Search: 435/6, 435/289, 436/43, 436/50, 436/55
• US Class Current: 435/6.16
• CPC Class Codes: 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
• CPC Class Codes: B01J 2219/00286 Reactor vessels with top and bottom openings
• CPC Class Codes: B01J 2219/00292 in the shape of pipette tips
• CPC Class Codes: B01J 2219/00315 Microtiter plates
• CPC Class Codes: B01J 2219/00423 using filtration, e.g. through porous frits
• CPC Class Codes: B01J 2219/00497 Features relating to the solid phase supports
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00502 Particles of irregular geometry
• CPC Class Codes: B01J 2219/0059 Sequential processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00689 using computers
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01L 7/52 with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: C40B 40/06 Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 40/10 Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: G01N 2035/1055 for immobilising reagents, e.g. dried reagents
• CPC Class Codes: G01N 35/028 having reaction cells in the form of microtitration plates
• CPC Class Codes: G01N 35/109 with two horizontal degrees of freedom
• CPC Class Codes: Y10T 436/11 : Automated chemical analysis
• CPC Class Codes: Y10T 436/115831 : Condition or time responsive
• CPC Class Codes: Y10T 436/12 : Condition responsive control

Abstract

Procedures such as oligonucleotide, peptide or protein syntheses or sequencing, or immunological or other biospecific assays involving long sequential series of chemical reactions are performed on a solid phase support retained in a pipette tip. The manipulations involved in bringing the solid support into contact with the various reagents or reactants involved in the procedure are performed and controlled by automated instrumentation.

Claims

1. A method for performing a sequential series of reactions on a chemical species, said method comprising:

(a) immobilizing said chemical species on a solid support retained in a pipette tip mounted on an automated apparatus which is programmable to draw reactants into said pipette tip from receptacles at preselected locations and to expel reactants from said pipette tip in accordance with a preselected time sequence;

(b) placing said reactants in liquid form in said receptacles; and

(c) causing said apparatus to draw said reagents into said pipette tip in accordance with a preselected sequence to contact said chemical species so immobilized, thereby causing said sequential series of reactions to occur.

2. A method in accordance with claim 1 in which said reactants are nucleosides, and said sequential series of reactions are sequential coupling reactions to form an oligonucleotide.

3. A method in accordance with claim 1 in which said reactants are amino acids, and said sequential series of reactions are sequential coupling reactions to form a peptide or protein.

4. A method in accordance with claim 1 in which said reactants are biospecific binding members, and said sequential series of reactions collectively comprise a biospecific binding assay.

5. A method in accordance with claim 1 in which said solid support is selected from the group consisting of polystyrene and silica.

7. A method in accordance with claim 1 further including drawing a reagent into said pipette tip which has the characteristic of reacting with and separating said chemical species which has been subject to said sequential series of reactions from said solid support.

6. A method for automatically performing a sequential series of reactions on a chemical species using an automated laboratory workstation operating on a pipette, comprising the steps of:

configuring a pipette tip on the pipette, said pipette tip retaining a solid phase support therein, said solid phase support being of a material capable of immobilizing a chemical species;

configuring receptacles on the automated laboratory workstation containing different reagents required for a desired sequence of reactions;

programming the automated laboratory workstation to aspirate reagents into and dispense reagents from the pipette tip in sequence to cause the immobilized chemical species to react with the reagents in the pipette tip in accordance with the desired sequence of reactions.