Various embodiments are directed to using nuclease expression in tissues that influences cell-free DNA end signatures/motifs and size of overhang between DNA strands. Embodiments can identify a nuclease that is being differentially regulated in abnormal cells relative to normal cells. Embodiments can determine that the nuclease preferentially cuts DNA into DNA molecules having: (i) a particular sequence end signature; or (ii) a specified length of overhang between a first strand and a second strand. A parameter can be determined for a biological sample based on an amount of DNA molecules that include an end sequence corresponding to the particular sequence end signature and/or a measured property correlating to the specified length of overhang. The parameter can be used to determine a characteristic of a tissue type, a fractional concentration of clinically-relevant DNA molecules, or a level of abnormality of a tissue type in the biological sample.

A novel combinatorial and high-throughput platform that enables rapid screening of complex and heterogeneous copolymer brushes as enzyme immobilization supports named Combinatorial High-throughput Enzyme Support Screening (CHESS). Using a 384 well-plate format, we synthesized arrays of three-component polymer brushes in the microwells using photo-activated surface-initiated polymerization, and immobilized enzymes in situ. The utility of CHESS to identify optimal immobilization supports under thermally and chemically denaturing conditions was demonstrated using Bacillus subtilis Lipase A (LipA). The identification of supports with optimal compositions was validated by immobilizing LipA on polymer-brush modified biocatalyst particles. We further demonstrated that CHESS could be used to predict the optimal composition of polymer brushes a priori for the previously unexplored enzyme, alkaline phosphatase (AlkP). Our findings demonstrate that CHESS represents a predictable and reliable platform for dramatically accelerating the search of chemical compositions for immobilization supports and further facilitate the discovery of biocompatible and stabilizing materials.