Microdroplet dispensing for a medical diagnostic device

• US 6,830,934 B1
• Filed: 12/03/1999
• Issued: 12/14/2004
• Est. Priority Date: 06/15/1999
• Status: Expired due to Term

• Current Assignee: Cilag Gmbh International (Johnson & Johnson), LifeScan IP Holdings, LLC
• Original Assignee: Lifescan Incorporated (Duv Holding Corporation)
• Inventors: Harding, Ian A., Leung, Lewis, Shartle, Robert Justice, Renowitzky, Glenn
• Primary Examiner(s): ALEXANDER, LYLE
• Application Number:
  US09/454,196
• Time in Patent Office: 1,838 Days
• Field of Search: 422/56, 422/58, 422/61, 436/164, 436/169, 436/166, 347/98, 427/2.11, 530/351, 435/174
• US Class Current: 436/166
• CPC Class Codes: B01L 2200/0621 Control of the sequence of chambers filled or emptied
• CPC Class Codes: B01L 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0822 Slides
• CPC Class Codes: B01L 2300/0825 Test strips
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/087 Multiple sequential chambers
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0688 surface tension valves, capillary stop, capillary break
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/502707 characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: B05D 3/00 Pretreatment of surfaces to which liquids or other fluent materials are to be applied; After-treatment of applied coatings, e.g. intermediate treating of an applied coating preparatory to subsequent applications of liquids or other fluent materials successively applying liquids or other fluent materials B05D1/36; drying ovens F26B
• CPC Class Codes: G01N 21/8483 Investigating reagent band test-element handling not specific to a test method G01N33/4875; analytical elements specific to chemical analysis of biological material G01N33/52; autometer with reagent band G01N35/04
• CPC Class Codes: G01N 2333/7454 Tissue factor (tissue thromboplastin, Factor III)
• CPC Class Codes: G01N 2333/96447 Factor VII (3.4.21.21)
• CPC Class Codes: G01N 33/4905 Determining clotting time of blood by chemical methods G01N33/86, C12Q1/56
• CPC Class Codes: G01N 33/521 Single-layer analytical elements
• CPC Class Codes: G01N 33/525 : Multi-layer analytical elements
• CPC Class Codes: G01N 33/5304 : Reaction vessels, e.g. agglutination plates for solid-phase systems G01N33/543
• CPC Class Codes: G01N 33/54386 : Analytical elements
• CPC Class Codes: G01N 33/54388 : based on lateral flow
• CPC Class Codes: G01N 33/558 : using diffusion or migration of antigen or antibody immunochromatographic test strips G01N33/54387
• CPC Class Codes: G01N 33/86 : involving blood coagulating time or factors, or their receptors

Abstract

A medical diagnostic device has a non-absorbent substrate that has a hydrophilic target area on which a reagent is deposited by non-impact printing of microdroplets. During deposition, the device is moved relative to the stream of microdroplets to form a substantially uniform reagent layer on the substrate. The device is particularly well adapted for measuring blood coagulation times. In a preferred embodiment, coagulation times are determined by monitoring the optical transmission of light through the target area as an applied blood sample interacts with the reagent.

Claims

1. A diagnostic reagent device for measuring an analyte concentration or characteristic of a biological fluid, including a non-absorbent substrate comprising:

a) a sample application area for accepting a sample of the biological fluid for analysis; and

b) a predetermined hydrophilic surface area for receiving, by nonimpact printing, a pulsed stream of microdroplets of a diagnostic reagent liquid comprising thromboplastin that interacts with the sample to cause in the sample a physically-measurable change that can be related to the analyte concentration or characteristic of the fluid.

2. The device of claim 1, in which the sample application area is located on said at least one hydrophilic surface area.

3. The device of claim 1, in which the substrate comprises a substantially transparent planar sheet.

4. The device of claim 1, in which the substrate comprises a substantially transparent thermoplastic sheet.

5. The device of claim 1, in which the reagent liquid comprises a colorant.

6. The device of claim 1, in which the predetermined hydrophilic surface area has a water contact angle of no more than about 60°

.

7. The device of claim 6, in which said water contact angle is about 25°

.

8. The device of claim 1, further comprising means for conveying the sample from the application area to the reagent area.

9. The device of claim 8, in which the means for conveying the sample from the application area to the reagent area comprises a top layer, separated from the substrate by an intermediate layer that has a through hole and adjoining channel cut into it, wherein the top layer, intermediate layer, and substrate form a bladder that, when compressed, and released causes a reduced pressure in the channel that draws blood into the reagent area.

10. The device of claim 9, in which the top layer has a hydrophobic surface facing the substrate, at least in the channel and reagent area.

11. A method for preparing a medical diagnostic reagent device, comprising the steps of

(a) providing a non-absorbent substrate having at least one hydrophilic target surface area,

(b) providing from a nonimpact print head onto a point within the hydrophilic surface area a pulsed stream of microdroplets of a diagnostic reagent liquid, in which the reagent liquid comprises thromboplastin,

(c) moving the substrate relative to the steam, and

(d) repeating steps b) and c) at least enough times to provide a substantially uniform layer of the liquid over the hydrophilic surface area.