Synthetic DNA-based data storage systems have received significant attention due to the promise of ultrahigh storage density and long-term stability. However, all known platforms suffer from high cost, read-write latency and error-rates that render them noncompetitive with modern storage devices. One means to avoid the above problems is using readily available native DNA. As the sequence content of native DNA is fixed, one can modify the topology instead to encode information. Here, we introduce DNA punch cards, a macromolecular storage mechanism in which data is written in the form of nicks at predetermined positions on the backbone of native double-stranded DNA. The platform accommodates parallel nicking on orthogonal DNA fragments and enzymatic toehold creation that enables single-bit random-access and in-memory computations. We use Pyrococcus furiosus Argonaute to punch files into the PCR products of Escherichia coli genomic DNA and accurately reconstruct the encoded data through high-throughput sequencing and read alignment.

A systematic microscopic analysis of the various resistive effects involved in the electronic detection of single biomolecules in a nanopore of a MoS2 nanoribbon is presented. The variations of the transverse electronic current along the two-dimensional (2D) membrane due to the translocation of DNA and protein molecules through the pore are obtained by model calculations based on molecular dynamics (MD) and Boltzmann transport formalism, which achieved good agreement with the experimental data. Our analysis points to a self-consistent interaction among ions, charge carriers around the pore rim, and biomolecules. It provides a comprehensive understanding of the effects of the electrolyte concentration, pore size, nanoribbon geometry, and also the doping polarity of the nanoribbon on the electrical sensitivity of the nanopore in detecting biomolecules. These results can be utilized for fine-tuning the design parameters in the fabrication of highly sensitive 2D nanopore biosensors.

Synthetic DNA-based data storage systems (1-11) have received significant attention due to the promise of ultrahigh storage density. However, all proposed systems suffer from high cost, read-write latency and error-rates that render them impractical. One means to avoid synthesizing DNA is to use readily available native DNA. As native DNA content is fixed, one may adopt an alternative recording strategy that modifies the DNA topology to encode desired information.Here, we report the first macromolecular storage paradigm in which data is written in the form of "nicks (punches)" at predetermined positions on the sugar-phosphate backbone of native dsDNA.The platform accommodates parallel nicking on multiple "orthogonal" genomic DNA fragments, paired nicking and disassociation for creating "toehold" regions that enable single-bit random access and strand displacement. As a proof of concept, we used the multiple-turnover programmable restriction enzyme Pyrococcus furiosus Argonaute (12) to punch files into the PCR

We describe a scalable device design of a dense array of multiple nanopores made from nanoscale semiconductor materials to detect and identify translocations of many biomolecules in a massively parallel detection scheme. We use molecular dynamics coupled to nanoscale device simulations to illustrate the ability of this device setup to uniquely identify DNA parallel translocations. We show that the transverse sheet currents along membranes are immune to the crosstalk effects arising from simultaneous translocations of biomolecules through multiple pores, due to their ability to sense only the local potential changes. We also show that electronic sensing across the nanopore membrane offers a higher detection resolution compared to ionic current blocking technique in a multipore setup, irrespective of the irregularities that occur while fabricating the nanopores in a two-dimensional membrane.

We use the electronic properties of 2D solid-state nanopore materials to propose a versatile and generally applicable biosensor technology by using a combination of molecular dynamics, nanoscale device simulations, and statistical signal processing algorithms. As a case study, we explore the classification of three epigenetic biomarkers, the methyl-CpG binding domain 1 (MBD-1), MeCP2, and γ-cyclodextrin, attached to double-stranded DNA to identify regions of hyper- or hypomethylations by utilizing a matched filter. We assess the sensing ability of the nanopore device to identify the biomarkers based on their characteristic electronic current signatures. Such a matched filter-based classifier enables real-time identification of the biomarkers that can be easily implemented on chip. This integration of a sensor with signal processing architectures could pave the way toward the development of a multipurpose technology for early disease detection.