Abstract: A secondary plasma device (SPD) and methods for its use with apheresis machines or similar extracorporeal blood processing systems and capable of collecting cell-free nucleic acids (cfNA) directly from a subject's circulating plasma, the SPD comprising: i. a sterile capsule having an inlet port and an outlet port and enclosing a filtration/adsorption medium, and configured to receive plasma from the extracorporeal blood processing circuit through the inlet port, such that plasma enters under pressure and flows through the filtration/adsorption medium then exits through the outlet port to a return path of the extracorporeal blood processing circuit leading back to the subject; and ii. the filtration/adsorption medium bearing fixed positive charge that captures cfNA from plasma by anion exchange, and from which cfNA can be subsequently recovered in quantities 10 to 1000-fold greater than the amount of cfNA contained in a 5 ml venipuncture specimen of the subject's blood.