FLUIDICS SYSTEM FOR SEQUENTIAL DELIVERY OF REAGENTS

• US 20100300559A1
• Filed: 05/24/2010
• Published: 12/02/2010
• Est. Priority Date: 10/22/2008
• Status: Active Grant

• Current Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Original Assignee: ION Torrent Systems Incorporated (Thermo Fisher Scientific Incorporated)
• Inventors: Schultz, Jonathan, Marran, David
• Granted Patent: US 8,546,128 B2
• Time in Patent Office: Days
• US Class Current: 137/561A
• CPC Class Codes: B01J 2219/00389 Feeding through valves
• CPC Class Codes: B01J 2219/00394 in multiple arrangements
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/0874 Three dimensional network
• CPC Class Codes: B01L 2300/0877 Flow chambers
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/502 with fluid transport, e.g. in multi-compartment structures centrifugal-type cuvettes G01N21/07; analysis by separation into components G01N30/00; automatic analysers G01N35/00
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 3/502738 characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B01L 3/502746 characterised by the means for controlling flow resistance, e.g. flow controllers, baffles B01L3/502738 takes precedence
• CPC Class Codes: B01L 3/502769 characterised by multiphase flow arrangements
• CPC Class Codes: B01L 3/502776 specially adapted for focusing or laminating flows
• CPC Class Codes: B01L 3/52 Containers specially adapted for storing or dispensing a reagent B01L3/02 takes precedence; containers for medical or pharmaceutical purposes A61J1/00; containers in general B65D; storing or dispensing test elements G01N33/4875; automated reagent dispensing G01N35/1002
• CPC Class Codes: C12Q 1/6869 Methods for sequencing
• CPC Class Codes: C12Q 2527/119 : pH
• CPC Class Codes: C12Q 2565/629 : being a microfluidic device
• CPC Class Codes: G01N 27/447 : using electrophoresis
• CPC Class Codes: G01N 35/1002 : Reagent dispensers
• CPC Class Codes: G01N 35/1097 : characterised by the valves valves in general F16K
• CPC Class Codes: Y10T 137/0318 : Processes
• CPC Class Codes: Y10T 137/0424 : Liquid cleaning or flushing
• CPC Class Codes: Y10T 137/85938 : Non-valved flow dividers

Abstract

The invention provides a passive fluidics circuit for directing different fluids to a common volume, such as a reaction chamber or flow cell, without intermixing or cross contamination. The direction and rate of flow through junctions, nodes and passages of the fluidics circuit are controlled by the states of upstream valves (e.g. opened or closed), differential fluid pressures at circuit inlets or upstream reservoirs, flow path resistances, and the like. Free diffusion or leakage of fluids from unselected inlets into the common outlet or other inlets at junctions or nodes is prevented by the flow of the selected inlet fluid, a portion of which sweeps by the inlets of unselected fluids and exits the fluidics circuit by waste ports, thereby creating a barrier against undesired intermixing with the outlet flow through leakage or diffusion. The invention is particularly advantageous in apparatus for performing sensitive multistep reactions, such as pH-based DNA sequencing reactions.

Claims

1. A fluidics circuit for controlling a plurality of fluid flows, the fluidics circuit comprising:

a fluidics node having an outlet and a plurality of fluid inlets; and

at least one waste port in fluid communication with the fluidics node by one or more passages each having a fluid resistance, the fluid resistances of the passages being selected so that whenever a fluid flows solely through a single fluid inlet to form a flow in the fluidics node a portion of such fluid exits the fluidics node through the outlet and the remainder of such fluid exits the fluidics node through the one or more passages, such that any fluid entering the fluidics node from unselected inlets is directed through the one or more passages to the one or more waste ports.

2. The fluidics circuit of claim 1 wherein said fluid inlets of said plurality are radially disposed about said outlet.

3. The fluidics circuit of claim 1 wherein said flow formed in said fluidics node is a laminar flow.

4. The fluidics circuit of claim 3 wherein said fluidics node has opposing and perpendicular surfaces.

5. The fluidics circuit of claim 4 wherein said plurality of said inlets are disposed in a surface of said node perpendicular to said surface in which said outlet is disposed.

6. The fluidics circuit of claim 4 wherein said plurality of said inlets are disposed in a surface of said node opposite to said surface in which said outlet is disposed.

7. The fluidics circuit of claim 6 wherein said passages in communication with said one or more waste ports are disposed in surfaces perpendicular to those in which said outlet and said plurality of said fluid inlets are disposed.

8. The fluidics circuit of claim 1 further comprising a waste conduit providing fluid communication to said one or more waste ports and a plurality of said passages radially disposed about said fluidic node and providing fluid communication between said fluidics node and the waste conduit, each said passage having a single said fluid inlet, and each portion of said passage distal to said node from said fluid inlet having a fluid resistance selected so that whenever a fluid flows solely through a single fluid inlet to form said laminar flow in said fluidics node a portion of such fluid exits the fluidics node through said outlet and said remainder of such fluid exits said fluidics node through said passages without fluid flows to the waste conduit.

9. An apparatus for sequentially delivering a plurality of reagents to a common volume, the apparatus comprising:

a fluidics circuit comprising a fluidics node having an outlet and a plurality of reagent inlets;

and at least one waste port in fluid communication with the fluidics node by one or more passages each having a fluid resistance, the fluid resistances of the passages being selected so that whenever a reagent flows solely through a single reagent inlet to form a laminar flow in the fluidics node a portion of such reagent exits the fluidics node through the outlet and the remainder of such reagent exits the fluidics node through the one or more passages, thereby directing any reagent entering the fluidics node from inlets without reagent flows through the one or more passages to the one or more waste ports;

a plurality of reagent valves each disposed in a conduit connecting a reagent inlet and a reagent reservoir; and

a control system for generating signals to open or close each of the plurality of reagent valves so that preselected reagent valves are opened for preselected durations with all other reagent valves closed, thereby delivering a predetermined sequence of reagent flows through the outlet.

10. The apparatus of claim 9 further including a wash inlet and a wash valve, the wash inlet being connected to said outlet so that the wash inlet is in fluid communication with said fluidics node through said outlet, and the wash valve being operationally associated with said control system and being disposed in a conduit connecting the wash inlet to a wash fluid reservoir, such that whenever said control system opens the wash valve and simultaneously closes all of said reagent valves, wash solution flows through said fluidics node, through said one or more passages, and to said one or more waste ports.

11. The apparatus of claim 10 further comprising a waste conduit providing fluid communication to said one or more waste ports and a plurality of said passages radially disposed about said fluidics node and providing fluid communication between said fluidics node and the waste conduit, each said passage having a single said fluid inlet, and each portion of said passage distal to said fluidics node from said fluid inlet having a fluid resistance selected so that whenever a fluid flows solely through a single fluid inlet to form said laminar flow in said fluidics node a portion of such fluid exits the fluidics node through said outlet and said remainder of such fluid exits said fluidics node through said passages without fluid flows to the waste conduit.

12. An apparatus for performing multi-step electrochemical processes, the apparatus comprising:

a reaction vessel coupled to an electronic sensor for monitoring products in the reaction vessel;

a fluidics system including a fluidics circuit for sequentially delivering a plurality of different electrolytes including a selected electrolyte to the reaction vessel; and

a reference electrode in contact with the selected electrolyte for providing a reference voltage to the electronic sensor, the reference voltage being provided without the reference electrode contacting the unselected electrolytes.

13. The apparatus of claim 12 wherein said fluidics circuit comprises a fluidics node having an outlet and a plurality of fluid inlets, and at least one waste port in fluid communication with the fluidics node by one or more passages each having a fluid resistance, the fluid resistances of the passages being selected so that whenever an electrolyte flows solely through a single fluid inlet to form a flow in the fluidics node a portion of such electrolyte exits the fluidics node through the outlet and the remainder of such electrolyte exits the fluidics node through the one or more passages, such that any electrolyte entering the fluidics node from unselected inlets is directed through the one or more passages to the one or more waste ports.