We　report　on　a　simple　and　sensitive　protocol　for　quantitative　assay　of　Hg(II)　ions.　The　process　involves　the　following　steps:　A　thymine　(T)-rich　single-stranded　DNA(1)　is　used　to　modify　the　surface　of　a　well　of　a　microplate　by　the　use　of　biotin-avidin　interface　chemistry.　In　parallel,　clusters　of　gold　microspheres　with　a　core　containing　the　enzyme　invertase　were　prepared　and　modified,　via　thiol　chemistry,　with　a　second　T-rich　oligomer　(DNA(2)).　If　the　gold　clusters　incorporating　invertase　and　carrying　DNA(2)　are　added　to　the　DNA(1)　immobilized　in　the　wells　of　the　microplate,　no　interaction　will　occur　and　the　gold　cluster　will　be　removed　in　the　subsequent　washing　step.　If,　however,　Hg(II)　is　present　in　the　sample,　the　DNA　on　the　gold　clusters　incorporating　the　enzyme　invertase　will　bind　to　the　DNA　in　the　wells　due　to　the　formation　of　strong　T-Hg(II)-T　links　between　the　two　DNA　strands.　The　encapsulated　invertase　will　not　be　removed　in　the　following　washing　step.　Sucrose　is　added　in　the　next　step　along　with　invertase　which　will　hydrolyze　it　to　form　glucose　and　fructose.　The　quantity　of　glucose　formed　increases　with　the　quantity　of　Hg(II)　ions　present　in　the　sample.　The　glucose　generated　is　then　quantified　by　using　a　commercial　personal　glucometer.　Under　optimal　conditions,　the　signal　for　glucose　increases　with　Hg(II)　concentration　in　the　range　from　0.05　to　80　nM,　and　the　detection　limit　is　as　low　as　10　pM.　The　assay　has　good　repeatability　and　shows　an　intermediate　precision　of　down　to　7.5　%.　The　method　is　highly　specific　for　Hg(II)　over　other　metal　ions.　It　was　applied　to　the　determination　of　Hg(II)　in　naturally　contaminated　sewage　and　in　spiked　samples　of　drinking　water.　This　approach　has　a　wide　scope　of　application　in　that　it　may　be　extended　to　numerous　other　kinds　of　nanoparticles,　oligomer　interactions,　enzymes　and　ions.