GenapSys™ has developed a novel electrical-based platform capable of accurately detecting single base incorporations. The CMOS (Complementary Metal Oxide Semiconductor) chip-based detection modality allows the system to be compact, accessible, and affordable.

On the surface of the CMOS sequencing chip, there are millions of sensors, each designed to capture one clonally amplified bead. Every sensor consists of electrodes in close proximity to each other which contact the bead captured by that sensor. These sensors are tuned to detect minute changes in impedance modulation between the electrodes. Since nucleotide incorporation into a growing DNA strand increases the amount of charged molecules around the bead, it changes the impedance measured by the sensor. The magnitude of the impedance change is correlated to the total change in the charge of DNA molecules and their surrounding layers around the bead, which is correlated to the number of incorporated nucleotides.

While almost all other NGS technologies are based on transient measurements, our detection modality is based on steady state measurements. Due to its steady state nature, the signal stays constant and we can take multiple measurements to increase our precision and signal-to-noise (SNR) which significantly improves our base calling accuracy. Also, the design of the chip allows for very low cross-talk between the sensors which enables high density packing of the sensors.

The sequencing workflow starts with a clonally amplified population of DNA molecules. One nucleotide at a time is added and detected to see whether that nucleotide got incorporated opposite the DNA templates.

For each nucleotide flow, the signal jump information is summarized and the data analyzed by our base-calling algorithm to make accurate base calls, and to determine the number of incorporations at each flow. The output is a FASTQ file of base calls – one for each individual sensor.

The plot below contains a representative example of acquired data showing the distribution of measured differential signal across multiple nucleotide flows for a single template sequence. Flows that are expected to have nucleotide incorporations are highlighted in red. Non-incorporating flows are shown in blue and do not deviate significantly from the baseline. The inferred sequence, including the number of nucleotides in each incorporation are shown below.