Devices, systems and methods for ultra-low volume liquid biopsy

Abstract

Provided herein are devices, systems, kits and methods for obtaining genetic information from cell-free fetal nucleic acids in ultra-low amounts of biological samples. Due to the convenience of obtaining ultra-low amounts of samples, devices, systems, kits and methods can be at least partially employed at a point of need.

What is claimed is: 
     
         1 . A method comprising:
 (a) obtaining or providing capillary blood comprising cell-free nucleic acids obtained from a subject;   (b) separating plasma or serum from the capillary blood or a portion thereof, thereby generating a plasma or serum sample;   (c) extracting cell-free nucleic acids from the plasma or serum sample; and   (d) detecting an overrepresentation, an underrepresentation, or a normal representation of at least one target nucleic acid sequence in the cell-free nucleic acids.   
     
     
         2 . The method of  claim 1 , wherein the extracting of (c) comprises binding the cell-free nucleic acids to a solid support. 
     
     
         3 . The method of  claim 2 , wherein the solid support is selected from the group consisting of: a bead, a nanoparticle, a magnetic particle, a chip, a microchip, a fibrous strip, a polymer strip, a membrane, a matrix, a column, a plate, and any combination thereof. 
     
     
         4 . The method of  claim 2 , further comprising, eluting the cell-free nucleic acids from the solid support. 
     
     
         5 . The method of  claim 4 , further comprising, purifying the cell-free nucleic acids. 
     
     
         6 . The method of  claim 1 , wherein the separating of (b) comprises centrifuging the capillary blood, filtering the capillary blood, or both. 
     
     
         7 . The method of  claim 1 , wherein the detecting of (d) comprises sequencing the at least one target sequence in the cell-free nucleic acids. 
     
     
         8 . The method of  claim 1 , wherein the plasma or serum sample is generated upon or after obtaining the capillary blood sample from the subject. 
     
     
         9 . The method of  claim 1 , wherein a total volume of the capillary blood is from about 5 μL to about 1 mL. 
     
     
         10 . A method comprising:
 (a) obtaining or providing a capillary blood sample comprising cell-free nucleic acids obtained from a subject;   (b) enriching for cell-free nucleic acids thereby generating enriched cell-free nucleic acids; and   (c) detecting an overrepresentation, an underrepresentation, or a normal representation of at least one target sequence in the enriched cell-free nucleic acids.   
     
     
         11 . The method of  claim 10 , wherein the enriching comprises removing a first amount of blood from the capillary blood sample. 
     
     
         12 . The method of  claim 10 , wherein the enriching comprises enriching for a target sequence present in the cell-free nucleic acids. 
     
     
         13 . The method of  claim 10 , wherein the enriching comprises enriching for fetal cell-free nucleic acids. 
     
     
         14 . The method of  claim 10 , wherein the enriching comprises removing white blood cells and/or cellular nucleic acids from the capillary blood sample. 
     
     
         15 . The method of  claim 10 , wherein a total volume of the capillary blood is from about 5 μL to about 1 mL. 
     
     
         16 . A method comprising:
 (a) obtaining or providing capillary blood comprising cell-free nucleic acids obtained from a subject;   (b) separating plasma or serum from the capillary blood or a portion thereof;   (c) extracting cell-free nucleic acids from the plasma or serum;   (d) detecting at least one target nucleic acid sequence present in the cell-free nucleic acids; and   (e) identifying one or more genetic or chromosomal abnormalities based on the detecting of (d).   
     
     
         17 . The method of  claim 16 , wherein the detecting of (d) comprises sequencing the at least one target nucleic acid sequence. 
     
     
         18 . The method of  claim 16 , wherein the subject is pregnant with a fetus. 
     
     
         19 . The method of  claim 18 , wherein the cell-free nucleic acids comprise fetal cell-free nucleic acids. 
     
     
         20 . The method of  claim 19 , wherein the one or more genetic or chromosomal abnormality comprises a fetal aneuploidy or a fetal chromosomal abnormality. 
     
     
         21 . The method of  claim 16 , wherein the subject has, is suspected of having, or is at risk of developing cancer. 
     
     
         22 . The method of  claim 16 , wherein the capillary blood is obtained from the subject by use of a transdermal puncture device.