Magnetoresistive sensor for real-time single nucleotide polymorphism genotyping

• We present a new magnetoresistive sensor platform with a local negative reference.
• Magnetic labels are magnetised by the field due to the sensor bias current.
• The negative reference ensures that only specifically bound targets are measured.
• We achieve real-time DNA detection over two orders of magnitude, down to 156 pM.
• We demonstrate real-time SNP genotyping with high quality and fast results.

We demonstrate a magnetoresistive sensor platform that allows for the real-time detection of point mutations in DNA targets. Specifically, we detect point mutations at two sites in the human beta globin gene. For DNA detection, the present sensor technology has a detection limit of about 160 pM and a dynamic range of about two orders of magnitude. The sensors are based on a new geometry for biological sensing that detects the difference between the amount of beads bound to a sensing pad and a local integrated negative reference pad. The magnetic beads are magnetised by the magnetic field arising from the sensor bias current such that no external magnetic fields are needed. The sensors are integrated in a microfluidic system with temperature control. The local negative reference integrated in the sensor geometry efficiently compensates for sensor offsets, external magnetic fields and a uniform background of magnetic beads, which enables real-time quantification of the specific binding of magnetic beads to the sensor surface under varying experimental conditions.