A method for detecting nucleic acid sequences in two or more collections of nucleic acid molecules, the method comprising: (a) providing an array of modified polynucleotides bound to a solid surface, each said modified polynucleotide comprising a determinable nucleic acid; (b) contacting the array of modified polynucleotides with: (i) a first collection of labeled nucleic acid comprising a sequence substantially complementary to a nucleic acid of said array, and (ii) at least a second collection of labeled nucleic acid comprising a sequence substantially complementary to a modified polynucleotide of said array; wherein the first and second labels are distinguishable from each other; and (c) detecting hybridization of the first and second labeled complementary nucleic acids to nucleic acids of said arrays; wherein the modified oligonucleotides are characterized by a characteristic selected from the group consisting of (a) a binding affinity of at least about 1.25 times that of a corresponding, non-modified oligonucleotide, (b) a pH stability of at least one hour at 37 C at a pH in a range of about 0.5 to 10; and (c) a nuclease resistance of at least twice that of a naturally occurring oligonucleotide having the same sequence and number of bases.