383

Index a binary-coded decimal (BCD) code 236 actuator 125, 126 biocompatibility 125, 147, 166, 241, Adleman’s DNA computer 16–17 329 allosteric biosensors 64 biomolecular computing 1, 2, 3, 5, 15, allosteric effector 111, 113 353, 371, 381 allosteric inhibiter 113 (bio)molecular realizations 363 allosteric toehold 266 biomolecular scaffolds 80–81 𝛼-Hemolysin (𝛼HL) 331 biomolecular switches 105 7-amino-4-methyl coumarin (AMC) Black Hole Quencher 374 131 blocking amplitude 331 AND Boolean logic 68, 164 Boolean algebra 65, 279 3-AND gate 359, 360 Boolean logic gate 1, 2, 10, 88, 133, AND gate implementation 38 134, 140, 155, 156, 157, 164, 282, 3-AND logic gate operation 358 284, 362 anti-anti-terminator/anti-terminator Boolean operations 1, 113, 155, 279, hairpin (aat/at-HP) 255 363 anti-fuel strand complementary 270 branch migration 97, 158, 248, 249, anti-gRNA bind 257 254, 258, 265–268, 282, 285, 287, antioxidant indicator 241 297, 298 application-specific integrated circuits Broccoli RNA aptamer 68–70 (ASICs) 39 aptamer–fluorophore complex 61 c aptamer ligand binding 125 cadmium chalcogenide semiconductors Arbona’s biophysical model 313 159 arithmetic DNA logic devices carbon dots (CDs) 159, 174–175 full-adder, full-subtractor 234 Cas9 + gRNA 255 half-adder, half-subtractor 232–234 catalytic hairpin assembly (CHA) 131, asynchronization circuits 38 261 asynchronous circuits 38 cationic conjugated polymers (CCPs) automatic writing–reading DNA 176 processes 9, 10 cell entry vehicles 81, 82 Cello computing language 7 b cellular environment 93, 251, 281, 285, bi-dynamic DNA origami 289 nanostructures 309 central processing unit (CPU) 275

DNA- and RNA-Based Computing Systems, First Edition. Edited by Evgeny Katz. © 2021 WILEY-VCH GmbH. Published 2021 by WILEY-VCH GmbH. 384 Index

Chao’s model 24 deoxyribozyme 46, 96, 293, 359 chemical reaction network (CRN) deoxyribozyme gate-based theory 31, 32, 35, 287 computational systems 362 application-specific integrated deoxyribozyme ligase-based 2iAND gate circuits (ASICs) 39 46 chemical reaction computer 31 deoxyribozyme logic gates 46–47, 50, complex functional computing 280–282, 357 systems 32 depletant molecule 119 decoding signal 37 3,5-difluoro-4-hydroxybenzylidene encoding 35, 37 imidazolinone (DFHBI) 138 history-free method 33 3,5-difluoro-4-hydroxybenzylidene-1- LDPC and polar codes 39 trifluoroethyl-imidazolinone mapping methods 31 (DFHBI-1T) 138 mass action kinetics 35 N-digit binary string 23 stochastic chemical reaction networks digital signal processing (DSP) modules (SCRNs) model 31 39 clustered regularly interspaced short direct representation, encoding 35 palindromic repeats (CRISPR) DNA-based digital data storage 83, 96, 255–258, 281 components of clustered regularly interspaced short data retrieval 348–349 palindromic repeats interference decoding 349–350 (CRISPRi) 257 encoding 346 communicating enzyme-DNA circuits storage 348 353 writing 346–348 computing core 241 density and coding capacity 345 concatenated logic circuits 232, durability and energy efficiency 345 239–240, 242 synthesis and sequencing conjugated polymers (CPs) 159, technologies 346 175–177 DNA-based logic gates 40, 157, 158, connecting DNA logic gates in circuits 171, 175, 266, 284, 379 deoxyribozymes 46–47 DNA catenanes 270 DNA strand displacement 47–50 DNA circuit construction techniques four-way junction (4WJ) 50–53 40 molecular computation field 45 DNA-coated QDs 160 construct multi-output circuits DNA computing system multifunctional probes 142 Adleman’s experiment 4, 5 signal transducers 138–141 advantages of 4, 329 contrary logic pairs 134, 241, 242 benefit of 379 conventional DNA computation 329 Cello computing language 7 CRISPR-Cas9 83, 86, 88, 95, 255 chemical structure of 3, 4 current-signal blockage 331 circuits application-specific integrated d circuits (ASICs) 39 data writing 346–348 clock signals 38 demultiplexer (DEMUX) 128, encoding representations 35 139–141, 144, 145 feed forward digital circuits 40 dendritic DNA strands 270 implementations 31–35 Index 385

logic gates 40 DNA hybridization 125 sequential digital logic circuits 38 DNA implementations conventional digital electronic chemical reaction networks (CRNs) computing 327 31, 32 developments in 6 diagrams of 35, 37 Adleman’s model 16 DNA strand displacement reactions challenges 27 34, 35 Chao’s model 24 stochastic chemical reaction networks DNA origami 24 (SCRNs) model 31 data storage 26 Turing machines 33 Lipton’s model 18 DNA keypad locks 236–238 Ouyang’s model 22 DNA logic circuits Sakamoto’s model 21 actuators 125 satisfiability (SAT) problem 16 arithmetic Smith’s model 19 full-adder, full-subtractor 234 DNA double helix 3, 5 half-adder, half-subtractor DNA logic circuits 231 232–234 DSD tool 7, 8 classification 231–232 future advancements of 380 concatenated 239–240 Hamiltonian path problem 327, 328 definition of 231–232 infancy 381 fluorescent signal design 125 information processing systems 3 innovative multifunctional DNA logic information storage systems 8 library 241 in vivo molecular computing devices intelligent bio-applications 241–244 329 logical principle 231–232 logic gate 329 non-arithmetic massive data 329 DNA keypad locks 236–237 microarrays 6, 7 DNA voter 236–237 motivation and application 1 encoders/decoders 235–236 nanopore decoding even/odd natural numbers 236 in medical diagnosis 335–338 multiplexers/demultiplexers rapid and label-free decoding 235–236 330–335 non-Boolean ternary logic gates nanorobots in living organisms 6 239 origami structures 6, 7 parity generator/checker (pG/pC) PCR method 9 error detection 237–238 second generation of 328 processors 125 switches 379 sensors 125 time-consuming process 329 universal input-output mechanism tic-tac-toe game 6 125, 126 travelling salesman problem 3, 6 DNA logic gates 45–53, 81, 85, 87, DNA dolphin-shaped structure 58 128, 130, 157–159, 175, 177, 239, DNA double helix 3, 5 241, 281, 282, 332, 360, 361, DNA gate motif 40 380 DNA G-quadruplex structures 107 DNA memory 8, 288, 381 DNA hairpin formation, Sakamoto’s DNA-MTC supramolecular logic model 21 platform 144, 145 386 Index

DNA nanoparticles 58 e DNA nanotechnology 58, 80, 83, 85, electrochemical analysis 117, 118 88, 89, 90, 92–95, 247, 250, 261, electrochemical impedance 265, 287–289, 293, 304 spectroscopy (EIS) 118 DNA origami transformers electronic computing kernel 87 applications 318–321 encoders/decoders 235, 236 bi-dynamic 308 endonuclease activity 88, 134, 296 biophysical models 307 energy transfer upconversion (ETU) design 312–316 mechanism 165 disadvantage of 309 engineering DNA switches 105, 379 experimental demonstrations allosteric activator 316–318 AND gate 113, 114 hybridization reactions 312 DNAzyme 113 nanostructures 77, 79, 307 OR gate 113, 114 Raman signal 308 allosteric effectors 111, 113 self-assembly 310 allosteric inhibiter 113 staple strand 310 conformational changes 108 static 308 DNA tetrahedron 115, 116 technique 58, 270 dose–response profile 118 2D rectangular 310 logic output function response zip and unzip primitives design 308 117–118 zippering process 312 population-shift mechanism 108, DNA recognition element 107–111, 109 114, 118 recognition element, input 107–108 DNA-related problems 328 steps 106 DNA secondary structure 57, 108, 126, structure-switching mechanism 111 127, 132, 136, 157, 159, 171, 176 entropy driven DNA networks 250 DNA strand displacement (DSD) enzyme-based computing 3 reactions bioelectronic interface DNA logic gates connections 47–50 3-AND gate 360 logic operations 40 binary operation 354 MNIST database 41 DNA-based reversible logic gates programming language 287 362–363 Rule 110 Automata 33, 34 Fredkin gate 363–368 switching circuits 41 logic systems 354, 355, 360–362 DNA-templated AgNCs 142, 170, 235 NADH 354 DNA tetrahedron 115, 116, 270 output signal 356–357 DNA translators 282–285 reactions catalyzed 354 DNA tweezer 268, 269 releasing electrode 354 DNA voter 236–237 reversible logic operations 363 DNA walker system 271 sensing electrode 354 DNAzymes 113 communicating enzyme-DNA history of 293–296 circuits 353 function 125 selective and sensitive receptors 353 dual-rail logic 49, 284 ET-based logic gates 158 dual-rail representation, encoding 35 even/odd natural numbers 234–236 Index 387 f framework nucleic acids (FNA) feed forward digital circuits 40 biomolecular engineering, living Feynman gate 373 systems (bio)molecular realizations 363 biomolecular scaffolds 80–81 oligonucleotides 373 cell entry vehicles 82 reversible DNA-based 368–371 error correction and resilience finite automaton system 329 84–85 first-generation riboregulators isothermal construction 83 251–252 logic units 81–82 fluorescence labeling 330 signal readout 84 fluorescence-producing targeting and editing 83 structure-switching molecular triggers and switches 84 107 definition 77, 80 fluorescence techniques 330 electronic computing kernel 87 fluorescent RNA motifs 81, 84, 90 environmental or cellular signals 92 fluorescent signal design information storage 90–91 construct multi-output circuits I/O and human-computer interfacing multi-functional probes 142 89–90 signal transducers 138–141 targeted applications DNA secondary structure cellular imaging 85–86 Hoogsteen hydrogen bond cellular pathway investigation 86 132–138 drug delivery 85 Watson–Crick hydrogen bond metabolic engineering 86 127–132 fraying 248 fluorogenic RNA aptamers Fredkin gate 365, 367, 368 biocomputing applications 59 (bio)molecular realizations 363 electrochemical and colorimetric bioelectronic interface 363–368 approach 61 reversible DNA-based 368–371 ligand 61 full-adder/full-subtractor 234 logic gate operations binary logic system development 64 g fluorescence (ON) and G4zyme substrates 134, 142 non-fluorescence (OFF) states gel electrophoresis 15–18, 21, 23, 96, 65 133, 328, 330, 360 MG-binding RNA aptamer 64 Gillespie-type stochastic simulations malachite green (MG)-binding RNA 248 61, 64 glucose-6-phosphate dehydrogenase nucleic acid 58–60 (G6PDH) 355, 356 properties 61, 62 gold nanoparticles (AuNPs) 166 types of 59 logic gates fluorophore experiments 35 colorimetric output 166–168 Fountain code 346, 349 photoluminescence quenching four-way junction (4WJ) 46, 50–53, 168–169 236, 237 surface plasmon resonance (SPR) fractional representation, encoding 166 35 G protein-coupled receptors 105 388 Index

G-quadruplex 77, 106–108, 126, light-sensitive DNA switches 107 132–137, 139–143, 145, 147, 158, light-up RNA aptamers 59, 65, 68 159, 165–167, 170, 172, 174, 176, Lipton’s model 18–19 232, 239, 266, 267 live-cell circuit 91, 92 logical redundancy 349 h logic units 45, 81–82, 87, 96, 136, 145, hairpin structure 51, 127–129, 251, 146, 148, 172, 285, 295 252, 315 loop-mediated isothermal amplification half-adder/half-subtractor 232–234 (LAMP) 131 Hamiltonian path problem (HPP) 3, low-density parity-check (LDPC) codes 15, 16, 96, 125, 213, 224, 275, 39, 349 277, 279, 327 hexokinase (HK) 356 m history-free method 33 majority logic gate (MAJ) 236 Hoogsteen hydrogen bond malachite green (MG) binding RNA aptamer–ligand interaction 138 aptamer 61 G-quadruplex 132–137 Broccoli aptamer 68, 69 i-motif 135, 136 co-transcriptional assembly Hopfield associative memory 41 verification 64 Human Genome Project 9 logic gate operations hybridization chain reaction (HCR) 82, 131, 319 AND logic gate 65–68 biochemical applications 65 i NAND and NOR gates 67, 68 i-motif 77, 106–108, 114, 115, 126, OR logic gate 65, 68 132, 135–137, 140, 143, 145, 147, YES and NOT gates 65 148 vibrational de-excitation 61 Illumina sequencers 349 maltose phosphorylase (MPh) 354, information processing systems 3, 10, 356 370 mammalian cells 58, 82, 87, 251, 257, inner filter effect (IFE) 165 258–261 innovative multifunctional DNA logic mass action kinetics 33, 35, 37 library 241 metal nanoclusters (NCs) 159, 3-input deoxyribozyme AND gate 169–171 (3-AND) 357–359 N-methyl-mesoporphyrin-IX (NMM) interleaved Reed–Solomon code 349 158 isothermal construction 81, 83 mfold tool 57, 68, 108, 115, 251 microdroplet system 331, 332, 335 l microRNAs (miRNAs) 161, 336, 337 lanthanide-based materials Möbius strip 309 energy transfer 163 Molecular Array of YES and AND gates logic gates, LLCs and lanthanide ions (MAYA) 294 163–164 molecular beacon (MB) probe 50, 125, luminescent lanthanide complexes 127 161–162 molecular biology processes 327 UCNPs logic gates 165 molecular/biomolecular information upconversion luminescence 165 processing 3 Index 389 molecular computing systems 1, 2, 41, non-Boolean ternary logic gates 239 371, 379 parity generator/checker (pG/pC) for molecular logic devices (MLD) error detection 237–238 Boolean logic gates 155 non-Boolean ternary logic gates 234, carbon-based nanomaterials, 235, 239 graphene oxide 171–174 nontraditional luminescent materials carbon dots (CDs) 174–175 156, 158–159, 178 conjugated polymers (CPs) 175–176 nontraditional quenching materials DNA molecular photonic logic gates 158 156–158 non-Watson–Crick base pairs 57 gold nanoparticles NP complexity 328 logic gates 166–168 nucleic acid surface plasmon resonance 166 hybridization 77 healthy/sick diagnosis 155 molecular photonic logic 156–158 lanthanide-based materials nanoparticles 57 energy transfer 163 nanostructure 77 logic gates, LLCs and lanthanide RNA aptamer 58–64 ions 163–164 strand displacement processes 247 luminescent lanthanide complexes NUPACK tool 57, 108 161–162 UCNPs logic gates 165 o upconversion luminescence 165 oligonucleotide DNA1 357 metal nanoclusters 169–170 ordinary differential equations (ODEs) nontraditional luminescent materials 35 158–159 Ouyang’s model 22–24 semiconductor QD nanocrystals OxDNA 248, 266 159–161 oxidized TMB (OxTMB) 241 silicon-based electronic analogs 155 molecular robotics 25, 45, 338 p Moore’s law 1, 2, 31, 275, 345 PAA-templated fluorescent AgNC logic multiplexers/demultiplexers 236 gates 171 multiplexer (MUX) 128, 145, 236 parallel processing 4, 15, 329 multistranded nucleic acid 77 parity generator/checker (pG/pC) for error detection 234, 235, 237 n photoluminescence (PL) 155 NAND gates 37, 115, 116, 175, 176 photonic molecular logic gates 156 nanopore-based platforms 349 polar codes 39 natural biological systems 88 polyethyleneimine (PEI) 354 natural structure-switching molecules polymerase chain reaction (PCR) 9, 105 15, 48, 328, 346 nerve cells 372, 373 population-shift model 110–112, 114 non-arithmetic DNA logic devices portable MinION sequencer 349 DNA keypad locks 236–237 PQQ-modified sensing electrode 355 DNA voter 236–237 probes with multi-role and multichannel encoders/decoders 236 148 even/odd natural numbers 236 protospacer adjacent motif (PAM) multiplexers/demultiplexers 236 255, 256 390 Index

pseudo-cooperative 119 s pyrimidine-uracil-nucleotide-purine Sakamoto’s model 21–22 (YUNR) motif 254 satisfiability modulo theory (SMT) 32 pyrroloquinoline quinone (PQQ) 354 satisfiability (SAT) problem 16, 18, 21, 278–279 q Scopoletin (SC) 244 quantum dots (QDs) seesaw gates 40, 47, 250, 283 aqueous media and conjugation 160 sequential digital logic circuits 38 cadmium chalcogenide shell/skeleton DNA/RNA frameworks semiconductors 159 77 ET-based signaling 160 short DNA oligonucleotides 65 logic gates 160–161 silicon-based computers 2, 15, 27, 41, photoluminescence 159 279, 329, 379, 380 silicon-based computing 15, 31 r single-molecule DNA navigator 24, 25 red-green-blue (RGB) oscillator 38 single-stranded DNA (ssDNA) 17, 83, regulating downstream effectors 105 107, 159, 187, 247, 258, 268, 269, 272, 294, 315, 331 reverse reaction 248 single-stranded nucleic acids 77 reversible DNA-based Feynman gate small-cell lung cancer (SCLC) 336 368–371 smallest biological computing device reversible signal modules 148 329 riboregulators 81, 84, 87, 88, 97, small interfering RNAs (siRNAs) 84 251–255, 260, 261 small regulatory RNAs (sRNAs) 260 ribosome binding site (RBS) 251, 253 small transcription activating RNAs riboswitches 77, 251, 260 (STARs) 255 RNA-based gene regulatory processes Smith’s model 19–21 251 solid-phase nucleotide synthesis 19 RNA biosensors 64 solid-phase translation 282, 284 RNA-cleaving deoxyribozymes (RCDZ) Spinach RNA aptamer 60, 64, 97, 201 46, 47 static DNA origami nanostructures RNA-cleaving DNAzymes 294 308, 309 RNA computing systems static nanostructures 308 advantages 4 stem-loop DNA switches 117 information processing systems 3 stochastic chemical reaction networks in vivo operation 4 (SCRNs) model 31 Turing machine 4 strand displacement 328 RNA folding process 57 strand displacement reaction (SDR) RNA interference (RNAi) technology 88, 129, 313 84, 260 analog computing 250 RNA nanotechnology 58, 80, 81, 91, basics 247–248 92, 95, 379 cellular chassis 250 rolling circle amplification (RCA) 94, CRISPR mechanisms 255–258 131 DNA-based molecular logic Rothemund’s rectangular origami autonomous DNA translators nanostructure 310 282–285 Rule 110 Automata 33, 34 Boolean operation 279 Index 391

catalytic systems for signal transcriptional and translational amplification 285–286 regulators 254–255 deoxyribozymes 280–282 systematic evolution of ligands by DNA computing exponential enrichment (SELEX) central processing unit (CPU) 275 58, 84, 107 Hamiltonian path problem 275 satisfiability (SAT) problem t 278–279 3,3′,5,5′-tetramethylbenzidine (TMB) dynamic reconfiguration, structural 165 devices 268–271 Theranostics 4, 77, 106, 133, 155, 177, entropy driven DNA networks 250 337, 338, 380 external control of 265–268 3D modeling software 58 future prospects for thioflavin T (ThT) 115, 133 DNA chemical reaction networks tic-tac-toe game 6, 46, 281, 329, 359 286–287 tile-based DNA nanostructure 77, 78 DNA nanotechnology, in vivo tile-integrated DNA circuits 52 287–289 toehold 97 kinetics and selectivity of 265 toehold binding 265, 268, 282, 314 mammalian cells 258–260 toehold exchange 82, 249, 250, 268, primitive computational operation 282, 283, 286 248 toehold-mediated strand displacement synthetic riboregulators (TMSD) reaction 125, 239, 247, first-generation riboregulators 249, 259, 260 251–252 disadvantage of 293 toehold switch riboregulator DNA duplex 284 252–254 kinetics of 267, 268 transcriptional and translational sequence-dependent DNA devices regulators 254–255 268 toehold exchange mechanism 268 structure-switching mechanism 111 solid-phase 284 structure-switching nanosystems 105, toehold sequestering technique 284 106 toehold switch riboregulator 252–254 surface-based DNA computing model traditional gel electrophoresis 330 16, 19 transcription activator-like effector surface-bound DNA sequence 20 nuclease (TALEN) 83 surface plasmon resonance (SPR) 166 travelling salesman problem 3, 6, 275 3+ sustained-chemical-oscillator-based trivalent lanthanide ions (Ln ) 161, synchronization mechanism 38 165 switching circuits 41 truth table 65, 66, 69, 132, 140, 144, synchronous circuits 38 157, 164, 232, 238, 243, 280, 281, synthetic chemical circuits 40, 379 360, 361, 364, 365, 369 synthetic molecular systems 1 turberfield incorporated hairpin motifs synthetic riboregulators 270 first-generation riboregulators Turing machines 4, 31–33, 35 251–252 Turing-universal 31, 32 toehold switch riboregulator two-input AND gate (2iAND) 46–49, 252–254 288, 295 392 Index

u Watson–Crick hydrogen bond unconventional information processing DNAzyme activity 128–129 379 hairpin structure/molecular bacon 5′ untranslated region (UTR) 84, 97, 127–128 251 strand displacement reaction unzip primitives 308, 313, 316, 318, 129–132 319 winner-take-all mechanism 41 upconversion luminescence (UCL) 165 y upconversion nanoparticles (UCNPs) YES-INH-1-2 decoder 241 159, 165, 241 z v zinc finger nuclease (ZFN) 83 vegetable aptamer 64 zippering process 311, 312 von Neumann-type computers 328 zipping staples 316, 318 zip primitives 308, 312, 313, 315 w Watson–Crick base-pairing 47, 57, 58, 80, 111, 113, 126, 155, 158, 293, 304