The seminal importance of DNA sequencing to the life sciences, biotechnology and medicine has driven the search for more scalable and lower-cost solutions. Here we describe a DNA sequencing technology in which scalable, low-cost semiconductor manufacturing techniques are used to make an integrated circuit able to directly perform non-optical DNA sequencing of genomes. Sequence data are obtained by directly sensing the ions produced by template-directed DNA polymerase synthesis using all-natural nucleotides on this massively parallel semiconductor-sensing device or ion chip. The ion chip contains ion-sensitive, field-effect transistor-based sensors in perfect register with 1.2 million wells, which provide confinement and allow parallel, simultaneous detection of independent sequencing reactions. Use of the most widely used technology for constructing integrated circuits, the complementary metal-oxide semiconductor (CMOS) process, allows for low-cost, large-scale production and scaling of the device to higher densities and larger array sizes. We show the performance of the system by sequencing three bacterial genomes, its robustness and scalability by producing ion chips with up to 10 times as many sensors and sequencing a human genome.DNA sequencing and, more recently, massively parallel DNA sequencing 1-4 has had a profound impact on research and medicine. The reductions in cost and time for generating DNA sequence have resulted in a range of new sequencing applications in cancer 5,6 , human genetics 7 , infectious diseases 8 and the study of personal genomes 9-11 , as well as in fields as diverse as ecology 12,13 and the study of ancient DNA 14,15 . Although de novo sequencing costs have dropped substantially, there is a desire to continue to drop the cost of sequencing at an exponential rate consistent with the semiconductor industry's Moore's Law 16 as well as to provide lower cost, faster and more portable devices. This has been operationalized by the desire to reach the $1,000 genome 17 .To date, DNA sequencing has been limited by its requirement for imaging technology, electromagnetic intermediates (either X-rays 18 , or light 19 ) and specialized nucleotides or other reagents 20 . To overcome these limitations and further democratize the practice of sequencing, a paradigm shift based on non-optical sequencing on newly developed integrated circuits was pursued. Owing to its scalability and its low power requirement, CMOS processes are dominant in modern integrated circuit manufacturing 21 . The ubiquitous nature of computers, digital cameras and mobile phones has been made possible by the low-cost production of integrated circuits in CMOS.Leveraging advances in the imaging field-which has produced large, fast arrays for photonic imaging 22 -we sought a suitable electronic sensor for the construction of an integrated circuit to detect the hydrogen ions that would be released by DNA polymerase 23 during sequencing by synthesis, as opposed to a sensor designed for the detection of photons. Although a variety ...
into visible light that are further captured and converted into electrical signals by a following photomultiplier. [7][8][9][10][11] Scintillators have been actively utilized for radiation detection applications in many fields, like nondestructive inspection, medical imaging, and space exploration. Scintillator-based X-ray detectors are advantageous in terms of cost and stability than direct X-ray detectors (a-Se), and the current market of X-ray detectors is dominated by scintillators.The light yield of scintillators, as one of the most important figures of merit, determines the X-ray conversion efficiency and detection contrast. Liu and co-workers reported the good X-ray imaging properties from CsPbBr 3 nanocrystals [8] and Zhang et al. evaluated the light yield for CsPbBr 3 nanocrystals as 21 000 photons per MeV. [11] Such value is still much lower than traditional scintillators like Lu 1.8 Y 0.2 SiO 5 -Ce (LYSO, 33 200 photons per MeV), [12] CsI-Tl (54 000 photons per MeV) [12] and Gd 2 O 2 S-Tb (GOS, 60 000 photons per MeV) [13] etc. The major reason is that the small Stokes shift and the self-absorption effect for lead halide perovskites would severely restrict the light outcoupling efficiency in films and crystals, which require large thickness for complete X-ray attenuations. For scintillators, large Stokes shift and high photoluminescence efficiency are required to obtain high scintillation light yield. The recently emerged self-trapped exciton emissions from low dimensional perovskites exhibit large stokes shift and high PLQY, and may provide efficient X-ray scintillations, but have scarcely been studied. [14][15][16] Another severe issue restricting the applications of lead halide perovskite scintillators is the toxicity of lead element. The ionic nature of halide perovskites and high solubility in water may seriously harm the human health as well as the environment. It is thus of great significance to find lead-free perovskites or halide scintillators.Here we present 1D structured Rb 2 CuBr 3 as one new member of scintillators with exceptionally high light yield. Rb 2 CuBr 3 is obtained by direct reaction between RbBr and CuBr with phase-purity, high quality, and good stability. Its 1D crystal structure and soft crystal lattice facilitate the formation of self-trapped exciton, which emits at 385 nm with a large Stokes shift of 85 nm (0.91 eV) and 98.6% photoluminescence quantum yield. The high emission efficiency, large Stokes shift, strong X-ray attenuation, and good spectrum matching with the photomultiplier tube (PMT) or silicon photomultiplier Scintillators are widely utilized for radiation detections in many fields, such as nondestructive inspection, medical imaging, and space exploration. Lead halide perovskite scintillators have recently received extensive research attention owing to their tunable emission wavelength, low detection limit, and ease of fabrication. However, the low light yields toward X-ray irradiation and the lead toxicity of these perovskites severely restricts their practical ...
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