A　novel　method　for　the　ultra　specific　and　sensitive　detection　of　DNA　in　biological　samples　was　described　in　this　paper　based　on　magnetic　beads　(MBs)-based　rolling　circle　amplification　combined　with　gold　nano-particles　(AuNPs)-aptamer　labeling　technique　and　inductively　coupled　plasma　mass　spectrometry　(ICP-MS)　detection.　The　proposed　assay　has　an　ultra-high　sensitivity　and　stability,　excellent　specificity　and　more　robust　resistibility　to　the　complex　matrix　due　to　the　utilization　of　MBs-based　rolling　circle　amplification,　AuNPs-aptamer　labeling　technique　and　ICP-MS　detection.　It　can　be　used　to　determine　DNA　or　single　nucleotide　polymorphisms　(SNP)　with　an　extremely　low　detection　limit　of　0.1　fM　(1.0　x　10(-16)　M)　and　a　discrimination　factor　for　single-base　mismatch　of　27.　The　proposed　assay　has　been　successfully　used　to　detect　DNA　in　serum　sample　with　a　recovery　of　91-106%　and　a　relative　standard　deviation　(RSD)　＜　6%　(n=6),　suggesting　that　our　method　is　sensitive　and　reliable.　The　ultra-high　sensitivity　and　specificity,　easiness　of　fabrication,　operational　convenience,　short　analysis　time,　better　stability　and　robust　resistibility　to　the　complex　matrix,　make　the　assay　a　promising　alternative　for　the　detection　of　various　DNA　sequence　in　the　clinical　diagnosis.　(c)　2014　Elsevier　B.V.　All　rights　reserved.