Method and apparatus for the discretization and manipulation of sample volumes

Abstract

Embodiments of the present invention relate to methods and apparatuses for the discretization and manipulation of sample volumes that is simple, robust, and versatile. It is a fluidic device that partitions a sample by exploiting the interplay between fluidic forces, interfacial tension, channel geometry, and the final stability of the formed droplet and/or discretized volume. These compartmentalized volumes allow for isolation of samples and partitioning into a localized array that can subsequently be manipulated and analyzed. The isolation of the discretized volumes along with the device's inherent portability render our invention versatile for use in many areas, including but not limited to PCR, digital PCR, biological assays for diagnostics and prognostics, cancer diagnosis and prognosis, high throughput screening, single molecule and single cell reactions or assays, the study crystallization and other statistical processes, protein crystallization, drug screening, environmental testing, and the coupling to a wide range of analytical detection techniques for biomedical assays and measurements. The minimal fluid interconnects and simple flow geometry makes the device easy to use and implement, economical to fabricate and operate, and robust in its operations.

What is claimed is: 
     
         1 . A method comprising:
 providing a fluidic lattice comprising,   a flow channel having a flow axis, and   a plurality of fluidic harbors in fluidic communication with the flow channel and offset from the flow axis;   flowing a volume of a first continuous liquid through the fluidic lattice to provide the first continuous liquid within the plurality of fluidic harbors; and   flowing a second continuous liquid through the fluidic lattice, the second continuous liquid immiscible with the first continuous liquid such that the second continuous liquid displaces the first continuous liquid from the flow channel while allowing the first continuous liquid to remain in the plurality of fluidic harbors wherein the second continuous liquid is flowed at a rate sufficient to displace some of the first liquid from at least one of the plurality of fluidic harbors.   
     
     
         2 . The method of  claim 1 , wherein at least one of the plurality of fluidic harbors is displaced in a vertical direction above the flow axis. 
     
     
         3 . The method of  claim 1 , wherein at least one of the plurality of fluidic harbors is displaced in a vertical direction below the flow axis. 
     
     
         4 . The method of  claim 1 , further comprising causing a contents of one of the plurality of fluidic harbors to mix with a chemical. 
     
     
         5 . The method of  claim 5 , wherein the mixing results from breaking down a wall between the one of the plurality of fluidic harbors, and a chamber containing the chemical. 
     
     
         6 . The method of  claim 6 , wherein the chamber is located out of a plane defined by the flow channel. 
     
     
         7 . The method of  claim 1 , further comprising removing a contents including the first liquid, from at least one of the plurality of fluidic harbors. 
     
     
         8 . The method of  claim 8 , wherein the contents are removed by flowing a third continuous liquid through the fluidic lattice, the third continuous liquid immiscible with the contents. 
     
     
         9 . The method of  claim 9 , wherein a viscosity of the third continuous liquid is different from a viscosity of the contents. 
     
     
         10 . The method of  claim 9 , wherein the third continuous liquid includes a surfactant. 
     
     
         11 . The method of  claim 8 , wherein the contents are removed by an application of force to the contents of the at least one of the fluidic harbors. 
     
     
         12 . The method of  claim 12 , wherein the force is selected from at least one of thermal energy, vacuum, pneumatic pressure, acoustic pressure, ultrasonic pulses, radiation pressure, electromagnetic field, electrowetting, photo-induced surface wetting, electrocapillarity, surface or interface tension, thermal-gradient-derived forces, electrostatic interaction, optical forces, or magnetic forces. 
     
     
         13 . The method of  claim 8 , wherein the contents are removed utilizing a valve. 
     
     
         14 . The method of  claim 8 , wherein the contents are removed by piercing the fluidic lattice with a needle. 
     
     
         15 . The method of  claim 8 , further comprising further manipulating the contents removed from the one of the plurality of fluidic harbors. 
     
     
         16 . The method of  claim 1 , wherein the first continuous liquid comprises an analyte. 
     
     
         17 . The method of  claim 16 , wherein the analyte is selected from the group consisting of a cell, a virus, a prion, a nucleic acid, a protein, a genetic material, an expressed product of a genetic material, a crystallizing molecule, and a particle. 
     
     
         18 . The method of  claim 16 , further comprising performing biochemical analysis on the analyte. 
     
     
         19 . The method of  claim 1 , further comprising performing digital polymerase chain reaction (PCR) within the plurality of fluidic harbors. 
     
     
         20 . The method of  claim 19 , further comprising sequencing a nucleic acid amplified within the plurality of fluidic harbors.