Integrated Analog Readout Array and Digital Backend for Mobile DNA Sequencing

DNA, a fundamental biomolecule, contains the genetic code that governs the development, functioning, and reproduction of all living organisms. It is composed of smaller molecular units called nucleotides. The process of determining the specific sequence of these nucleotides is known as DNA sequencing. An innovative approach to this is nanopore-based DNA sequencing. Unlike many other methods, nanopore sequencing detects DNA molecules directly, rather than relying on secondary phenomena, and can do so in real-time as the molecules pass through the device. This technology holds the potential to significantly democratize DNA sequencing, which could revolutionize medical diagnostics and personalized medicine, ultimately improving the lives of billions. This report focuses on optimizing the performance and cost-efficiency of nanopore-based sequencing, particularly by exploring the opportunities for implementing low-cost, integrated analog front-end arrays and application-specific accelerated digital back-end systems.

This thesis presents three iterative versions of a digital readout integrated circuit (DROIC), each enhancing throughput density through architectural and circuit-level advancements. The first version (DROICv1) employs a discrete-time (DT) amplifier with in-pixel successive approximation ADCs. The second version (DROICv2) increases throughput density using column-based ADCs. The third version incorporates an asynchronous reset amplifier, further enhancing throughput density by reducing amplifier noise.

To validate the system's functionality, the thesis demonstrates biological ion-channel and solid-state nanopore measurements. It also introduces methods for post-processing the chip to enable on-chip sensors. Finally, a RISC-V-based digital basecaller is presented, optimizing the speed and energy efficiency of the digital backend.