DEVICES, SYSTEMS AND METHODS FOR ULTRA-LOW VOLUME LIQUID BIOPSY
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.
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.