Periodic Reporting for period 1 - HYMEDNA (Hypermethylated DNA detection using NanoGaps)
Reporting period: 2015-10-01 to 2016-09-30
The HYMEDNA project aimed at commercialization of very sensitive point-of-care biosensors for early-stage cancer detection based on the electrical detection of hmDNA inside nanogaps.
Only recently the awareness has risen that local hypermethylation of DNA provides a generic marker for a wide range of cancers. A robust, simple and cheap method for detecting hmDNA at low concentrations would be a major step forward in the early-stage detection of cancer. Existing hmDNA detection relies on fluorescent read-out, which requires dedicated laboratory handling.
Our technology is based on electrodes separated by a tunable nanogap. The original idea was to trap hmDNA and highly concentrate it in between the electrodes using methyl binding domain (MBD) proteins. MBD binds specifically to methylated CpG sequences and thus provides the direct recognition of the targeted methylated moieties. During HYMEDNA we moved to a concept where hmDNA is first pre-concentrated, and afterwards detected in the nanogap using sequence-specific DNA trapping.
During HYMEDNA significant progress was made in the DNA metallization procedure. Multi-electrode sensors were realized with nanoscale gaps for trapping the DNA. Test DNA was prepared with relevant lengths of ~250 nm in combination with single-strand oligonucleotides that can be attached to the Au electrodes. Presently the effort concentrates on optimizing sensitivity and specificity of the nanoelectronic sensing method.