Single channel continuous flow system

• US 4,853,336 A
• Filed: 02/02/1987
• Issued: 08/01/1989
• Est. Priority Date: 11/15/1982
• Status: Expired due to Term

• Current Assignee: Technicon Instruments Corporation
• Original Assignee: Technicon Instruments Corporation
• Inventors: Smith, John L., Cassaday, Michael M., Herron, Rand E., Saros, Stephen, Pelavin, Milton H.
• Primary Examiner(s): NOT, DEFINED
• Application Number:
  US07/010,236
• Time in Patent Office: 911 Days
• Field of Search: 422/82, 422/81, 436/53, 436/52, 73/864.12, 73/864.21, 73/864.22, 73/861.05, 138/26, 366/106, 366/262, 366/139, 366/341, 324/453, 324/439, 55/15, 55/158
• US Class Current: 436/53
• CPC Class Codes: G01N 2035/0415 moving in two dimensions in a horizontal plane
• CPC Class Codes: G01N 2035/0443 for reagents
• CPC Class Codes: G01N 35/025 having a carousel or turntable for reaction cells or cuvettes
• CPC Class Codes: G01N 35/08 using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
• CPC Class Codes: Y10T 436/117497 with a continuously flowing sample or carrier stream
• CPC Class Codes: Y10T 436/118339 with formation of a segmented stream

Abstract

A continuous flow system is disclosed in which successive liquid segments are established containing different related components of a fluid package, such as an analysis mixture, separated by at least one immiscible segment, passed along a first section of a conduit, combined in a second section of the conduit and mixed while passing along a third section of the conduit, so as to provide a completely mixed segment. This system permits the delayed on-line mixing of different components of an analysis mixture, such as samples with reagents or diluents, as well as mixing and interaction of such components in a single conduit.

Claims

1. A method of reacting discrete liquid segments passing through sequential first, second and third sections of a single conduit, which method comprises the steps of:

(a) introducing and passing a first segment of a liquid sample and a second segment of a liquid reagent separated by a first gas segment into and along said first conduit section;

(b) forming the first gas segment to occlude said first conduit section to maintain the first and second liquid segments separate while in said first conduit section;

(c) rendering the first gas segment ineffective to occlude said second conduit section to combine in said second conduit section the first and second liquid segments, which had been previously maintained separate in said first conduit section, to provide a combined liquid segment;

(d) completely mixing the combined liquid segment in said third conduit section;

(e) receiving the completely mixed combined liquid segment and the gas segment from said third conduit section; and

(f) analyzing the completely combined liquid segment.

2. The method of claim 1 wherein said rendering step comprises removing the first gas segment through valving means in said second conduit section.

3. The method of claim 1 wherein said rendering step comprises forming said second conduit section of a diameter sufficient to render the first gas segment non-occlusive therein.

4. The method of claim 1 wherein said rendering step comprises removing a portion of the first gas segment from said second conduit section without removing liquid from the first and second liquid segments.

5. The method of claim 1 wherein said introducing step comprises introducing the first and second liquid segments and the first gas segment into a single probe connected to the inlet of said first conduit section.

6. The method of claim 5 wherein said introducing step comprises:

(a) introducing the first liquid segment mixed with a first reagent therefor;

(b) then introducing the first gas segment;

(c) then introducing the second liquid segment;

which comprises the additional steps of forming the second gas segment to occlude said first and second conduit sections and which combines with said first gas segment to occlude said third conduit segment and analyzing the completely mixed combined liquid segment.

7. A method for reacting and analyzing liquid segments in a stream of an alternating sequence of gas and liquid segments flowing along a single conduit, which method comprises:

(a) maintaining a continuous film of liquid fluorocarbon on the inner surface of a conduit having a single inlet and sequential first, second and third sections;

(b) introducing into said inlet a first liquid segment of about 1 ul of a blood serum sample to be analyzed and mixed with about 7 ul of a first reagent which is reactive therewith;

(c) following (b), introducing into said inlet a first air segment which is occlusive in said inlet and said first conduit section;

(d) following (c), introducing into said inlet a second liquid segment of about 7 ul of a second reagent which is reactive with a reaction product of the sample and the first reagent to give a detectable response;

(e) following (d), introducing into said inlet a second air segment which is occlusive in said inlet and said first, second and third conduit sections;

(f) maintaining the first and section liquid segments separated by the first gas segment while in said inlet and first conduit section;

(g) passing said first and second liquid segments which had been maintained separate in said first conduit section into said second conduit, said second conduit section being formed to have a diameter sufficient to render the first gas segment non-occlusive in said second conduit section;

(h) combining the first and second liquid segments in said second conduit section to provide a combined liquid segment;

(i) coalescing the first and second gas segments in said second conduit section to form a coalesced gas segment which is occlusive in said second and third conduit sections;

(j) completely mixing the combined liquid segment in said third conduit section; and

(k) analyzing the completely mixed combined liquid segment while passing through said third conduit section.

8. A single channel analytical system for analysis of selected liquid segments in a continuously flowing stream of an alternating sequence of gas and liquid segments, which system comprises:

(a) a single solid fluorocarbon conduit having an inner surface and having first, second and third sequential sections and a single inlet;

(b) a single probe in fluid communication with said conduit inlet;

(c) means cooperating with said conduit and said probe for maintaining on said inner surfaces of said conduit and said probe a continuous film of a liquid fluorocarbon;

(d) a pump cooperating with said conduit for introducing a fluid stream into said probe and passing said stream along said conduit through said inlet;

(e) a metering apparatus for introducing into said probe and first conduit section a plurality of test packages, each of which comprises a first liquid segment of about 1 ul of a blood serum sample to be analyzed mixed with 7 ul of a first reagent which is reactive therewith, a first air segment, which is occlusive in said first conduit section, a second liquid segment of about 7 ul of a second reagent which is reactive with a reaction product of said sample and said first reagent to give a detectable response, and a second air segment;

(f) means for combining the first and second liquid segments and for coalescing the first and second air segments comprising said second conduit section having a diameter sufficiently greater than that of said first conduit section to render the first gas segment non-occlusive, thereby combining the first and second liquid segments, which had been separately introduced into said inlet and previously maintained separate along said first conduit section to provide a combined liquid segment;

(g) said third conduit section comprising means for completely mixing the combined liquid segments; and

(h) means for analyzing the combined liquid segments along said third conduit section and comprising at least one colorimeter.

9. A system for continuous flow of an alternating sequence of gas and liquid segments, which system comprises:

(a) a conduit having an inner surface and having first, second and third sequential sections and a single inlet;

(b) means cooperating with said conduit for maintaining on said inner surface of said conduit a continuous film of an immiscible liquid which preferentially wets said inner surface to the exclusion of the gas and liquid segments;

(c) means for passing a fluid package comprising in sequence a first liquid segment, a first gas segment, a second liquid segment and a second gas segment through said inlet and along said first conduit section, one of the first and second liquid segments being a reagent or diluent liquid for the other of the first and second liquid segments which defines a liquid sample to be analyzed;

(d) means for combining the first and second liquid segments of the fluid package, which had been separately passed into said first conduit section and previously maintained separate therein, along said conduit section having completely closed walls, thereby permitting mixing of the first and second liquid segments while passing along said third conduit section to provide a combined liquid segment;

(e) said third conduit section comprising means for completely mixing the combined liquid segment therein; and

(f) means for receiving and analyzing the completely mixed liquid segment from said third conduit section.

10. The continuous flow system of claim 9 wherein the ratio range of the inner diameter of said first conduit section to said third conduit section is from about 1:

1.5 to about 1;

3, said first conduit section sized such that the first gas segment is occlusive therein, said second conduit section sized such that the first gas treatment is non-occlusive in at least a portion thereof and said third conduit section sized such that the first gas segment is non-occlusive therein.

11. The continuous flow system of claim 10 wherein said second conduit section is of a diameter greater than that of said first conduit section and sufficient to render the first gas segment non-occlusive.