Exponential Signal Amplification in CRISPR-Functionalized Graphene/Silicon Heterojunction Barristor for Ultrasensitive DNA Detection

Clustered regularly interspaced short palindromic repeats functionalized graphene field-effect transistors (CRISPR-GFETs) have shown outstanding performance in the detection of DNA sequences within intact genomic material. However, their sensitivity is limited by the zero-bandgap nature of graphene and the relatively weak conductance modulation in response to surface potential changes. Here, we report a highly sensitive DNA sensor array on a 4-inch silicon wafer based on a CRISPR-functionalized graphene/silicon heterojunction (CRISPR-G/Si) barristor. The graphene surface was functionalized through robust π–π stacking of K3-pyrene to enable specific immobilization of E3-fused dSpCas9 ribonucleoprotein (RNP) complex via K3-E3 coiled-coil interactions. This RNP-integrated platform facilitates recognition of target double-stranded DNA (dsDNA) sequences through programmable single-guide RNA (sgRNA)-guided binding. Target DNA induces n-type doping in graphene, raising its Fermi-level (E_F) and reducing the G/Si Schottky barrier height (SBH). Unlike conventional GFETs that rely on quadratic conductance changes via Fermi-level ((Formula presented.)), G/Si junctions exhibit an exponential conductance change via SBH modulation (σ∝exp(− Φ_SB)), enabling intrinsic signal amplification. The CRISPR-G/Si barristor demonstrates a wide dynamic range from 1 pM to 100 nm with a responsivity of 60%–865%, which is 10–100 times higher than conventional CRISPR-GFETs.