DNA multi-bit non-volatile memory and bit-shifting operations using addressable electrode arrays and electric field-induced hybridization

Abstract

DNA has been employed to either store digital information or to perform parallel molecular computing. Relatively unexplored is the ability to combine DNA-based memory and logical operations in a single platform. Here, we show a DNA tri-level cell non-volatile memory system capable of parallel random-access writing of memory and bit shifting operations. A microchip with an array of individually addressable electrodes was employed to enable random access of the memory cells using electric fields. Three segments on a DNA template molecule were used to encode three data bits. Rapid writing of data bits was enabled by electric field-induced hybridization of fluorescently labeled complementary probes and the data bits were read by fluorescence imaging. We demonstrated the rapid parallel writing and reading of 8 (2³) combinations of 3-bit memory data and bit shifting operations by electric field-induced strand displacement. Our system may find potential applications in DNA-based memory and computations.

Fig. 1

A DNA SLC-NVM system. a Random-access writing and reading operations using a microchip with an array of individually addressable electrodes. The specific cells are first selectively activated with the encoding ssDNA template molecules using the electrodes. The data bits of the cells are then written by EFH of fluorescently labeled bit-decoding DNA probes and read by fluorescence imaging. b, c A 6 × 6 SLC-NVM memory array. The addresses (b) and fluorescence image (c) of the array of cells after a writing operation had been performed on the selected cells. d–f Cell addressing specificity. Shown are the gray scale (d) and pseudo-color (e) fluorescence images, and fluorescence intensity (f) of three neighboring cells. Cell C₁ was activated and written by EFH while cells C₂ and C₃ were not activated. A potential was applied to C₂ but not C₃ during the writing of data to C_1. The bit status of cell C₁ is true since its fluorescence intensity is above the threshold value. The bit status of the two neighboring cells C₂ and C₃ remains false since their fluorescence intensity is below the threshold value. Scale bars are 80 µm

Fig. 2

A DNA TLC-NVM system. a Writing operations of three-bit cells. The three bits are encoded by three different segments on a DNA sequence. Illustrated is the writing of three different bits, one on each cell. b–d Fluorescence readouts of the three bits, LSB (b), SSB (c), and MSB (d). Scale bars are 80 µm

Fig. 3

A DNA multi-cell TLC-NVM system. a The addresses of an array of eight individually addressable three-bit memory cells and a null cell (S₀–S₈). b Possible combinations of the three encoding bits. c–e Status of the E₁ (c), E₂ (d), and E₃ (e) bits on the eight memory cells and the null cell. f Fluorescence intensity and written data of the eight memory cells. S₀–S₈: cell 1 to cell 9. ES: encoding sequence with three non-overlapping DNA segments, one for each of the three bits (LSB, SSB, and MSB). E₁: Cy3-labeled DNA probe to encode LSB. E₂: FAM-labeled probe to encode SSB. E₃: Cy5-labeled probe to encode MSB. Scale bars are 160 µm

Fig. 4

Bit shifting operations by electric field-induced DNA strand displacement. a Right shifting of 010 (SSB) to 001 (LSB) . b Right shifting of 100 (MSB) to 010 (SSB) . c Fluorescence readouts of bit shifting operations. The fluorescence  images show the readout data before (top panel, Cy5 channel) and after the parallel bit shifting (100–010) operation (middle panel, Cy5 channel, and bottom panel, FAM channel) on five three-bit cells