Method for the metered application of a biochemical analytical liquid to a target

• US 5,338,688 A
• Filed: 02/19/1993
• Issued: 08/16/1994
• Est. Priority Date: 08/02/1990
• Status: Expired due to Term

• Current Assignee: Nisshin Seifun Group Incorporated
• Original Assignee: Boehringer Mannheim GmbH (Roche Holding AG)
• Inventors: Babiel, Reiner, Deeg, Rolf, Maurer, Eberhard, Klose, Sigmar, Kopfer, Bernhard
• Primary Examiner(s): Housel, James C.
• Assistant Examiner(s): WALLENHORST, MAUREEN
• Application Number:
  US08/019,828
• Time in Patent Office: 543 Days
• Field of Search: 436/44, 436/46, 436/47, 436/54, 436/180, 436/422, 422/63, 422/65, 422/66, 422/81, 422/100, 222/146.5, 222/420, 346/75, 346/222, 239/13, 239/128, 239/133
• US Class Current: 436/180
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/0063 Other, e.g. van der Waals forces, hydrogen bonding
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00641 the porous medium being continuous, e.g. porous oxide substrates
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00677 Ex-situ synthesis followed by deposition on the substrate
• CPC Class Codes: B01L 3/0268 using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: G01N 2035/1041 Ink-jet like dispensers
• CPC Class Codes: G01N 35/00009 provided with a sample supporting tape, e.g. with absorbent zones
• CPC Class Codes: G01N 35/0099 comprising robots or similar manipulators robots per se B25J
• CPC Class Codes: G01N 35/1002 Reagent dispensers
• CPC Class Codes: Y10T 436/110833 Utilizing a moving indicator strip or tape
• CPC Class Codes: Y10T 436/112499 with sample on test slide
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

A method for the metered application of a biochemical analytical liquid to a target, wherein the liquid is ejected in small quantities on to the target through a jet from a jet chamber by a procedure in which a partial volume of the liquid in the jet chamber is evaporated and expanded for a short time whenever a quantity of the liquid is to be ejected. The invention further relates to a device with a disposable jet element which contains prepackaged analytical liquid.

Claims

1. A method for the metered application of a biochemical analytical liquid containing a heat-sensitive protein to a target, comprising the step of successively ejecting a plurality of quantities of the biochemical analytical liquid with high frequency from a jet chamber through a jet associated therewith onto the target by rapidly heating said biochemical analytical liquid by a heating element which is in thermal contact with said chamber for evaporating and expanding a part of the volume of the biochemical analytical liquid in the jet chamber so as to eject a predetermined quantity of the biochemical analytical liquid through the jet, wherein a majority of the heat-sensitive protein is not destroyed or denatured.

2. The method of claim 1, wherein the biochemical analytical liquid is a liquid reagent.

3. The method of claim 2, wherein the target is an analysis element reagent domain, a plurality of quantities of the biochemical analytical liquid reagent are successively ejected in droplet form to form dots in predetermined patterns on the reagent domain, and the jet and the analysis element are moved relative to one another in a manner such that the dots produced by the liquid reagent droplets on the reagent domain form a predetermined pattern in the reagent domain.

4. The method of claim 3, wherein a given dot produced by a droplet of liquid reagent on the reagent domain has a surface area of less than 2 mm².

5. The method of claim 3, wherein a plurality of different liquid reagents are each ejected from a separate jet chamber through separate jets onto the target.

6. The method of claim 5, wherein predetermined patterns produced from respective quantities of different liquid reagents applied to the reagent domain are essentially out of direct contact with adjacent predetermined patterns.

7. The method of claim 6, wherein the quantities of different liquid reagents form a pattern of alternating dots wherein quantities of different liquid reagents are adjacent to but spatially separated from each other.

8. The method of claim 1, wherein the protein contained in the biochemical analytical liquid is a member selected from the group consisting of an enzyme, an antibody, an antibody-enzyme conjugate, an antigen, and a hapten.

9. The method of claim 8, wherein the biochemical analytical liquid contains a binding protein.

10. The method of claim 1, wherein the target is a reaction vessel into which the biochemical analytical liquid is introduced.

11. The method of claim 1, wherein the biochemical analytical liquid which is ejected through the jet is in the form of a droplet and the biochemical analytical liquid which is evaporated and expanded is evaporated and expanded such that the increase in volume of the biochemical analytical liquid caused by the expansion is substantially the same as the volume of the droplet.

12. The method of claim 1, wherein the biochemical analytical liquid is member selected from the group consisting of a body fluid, a liquid reagent reactable with a body fluid, and a calibrating liquid.

13. The method of claim 12, wherein the target is a test carrier.

14. The method of claim 13, wherein the predetermined quantity of liquid ejected through the jet is no more than 2000 picoliters.

15. A method of analyzing a biological sample by measuring a physically measurable change caused by the reaction between a biological sample and a reagent containing a heat-sensitive protein which comprises the steps of:

ejecting a drop of the reagent through a jet of a jet chamber onto an analysis element by rapidly heating, evaporating and expanding a part of the volume of the reagent contained in the jet chamber, wherein said volume part is expanded in volume by an amount substantially corresponding to the volume of the drop and wherein a majority of the heat-sensitive protein in the reagent is not destroyed or denatured,

bringing the sample into contact with the reagent on the analysis element to cause said reaction, and

measuring said change.

16. A method of analyzing a biological sample by measuring a physically measurable change caused by the reaction between a biological sample and a liquid reagent containing a heat-sensitive protein comprising the steps of:

successively ejecting a plurality of quantities of said liquid reagent from a jet chamber through a jet associated therewith onto an analysis element reagent domain by heating, evaporating and expanding a part of the volume of the liquid reagent contained in the jet chamber, the plurality of quantities of the liquid reagent being successively ejected in droplet form to form dots on the reagent domain, the jet and the analysis element being moved relative to one another in a manner such that the dots produced by the liquid reagent droplets on the reagent domain form a predetermined pattern on the reagent domain and a majority of the heat-sensitive protein in the reagent not being destroyed or denatured;

conveying the analysis element to a sample delivery station;

bringing a sample into contact with the dots on the reagent domain; and

measuring any physically measurable change which occurs as a result of a reaction between the sample and the reagent.