From biology to circuitry: a review of DNA and other biomaterials as templates for nanoelectronic systems

Abstract

Bio-templated nanomaterial fabrication offers a novel and potentially low-cost approach for creating advanced electronic devices. By utilizing biomolecular templates, such as viruses, bacteria, carbohydrates, proteins, lipids, or nucleic acids, complex structures are formed through self-assembly, achieving control even at the nanometer scale. DNA, and DNA origami especially, stand out due to their programmability, self-assembly, and customizability, enabling the creation of sophisticated designs with applications in nanoelectronics. Viruses, particularly M13, have been employed as templates for creating devices, sensors, and materials. Additionally, bacteria, carbohydrates, polypeptides, and lipids exhibit promising potential for fabricating bioelectronic devices with biocompatibility and self-repairing functionality. Accompanying these significant advancements, challenges remain related to scalability, stability, and performance. This review provides an overview of recent developments in bio-templated nanoelectronics and highlights future research directions for improving electronic device fabrication through biological materials. We further present a comprehensive summary of the key advancements achieved in our laboratory over the past two decades, in utilization of DNA templates for the assembly of electronic components, with an emphasis on the design, assembly, and functionalization of DNA-based architectures.

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Introduction

Bio-templated fabrication of nanomaterials is a cutting-edge approach to assembling new structures that result in sophisticated devices at low cost.^1–4 By harnessing the unique properties and functionalities of these materials and templates, novel electronic, catalytic, or optical devices can be assembled from the bottom up to address limitations associated with top-down fabrication.^5,6 This self-assembly approach offers flexibility in design and fabrication, while providing precision, reliability, and biocompatibility with potential transformative applications in various fields.^6,7

Many biomolecules possess properties that allow them to serve as substrates, scaffolds, or components in self-assembly.^8–10 When used as templates, molecular entities allow for precise arrangements of nanoscale inorganic or organic materials.^11–14 Additionally, bio-templated constructs enable the scalability of electronic systems by integrating multiple components on a single device.¹⁵ Moreover, biosystems exhibit inherent mechanisms for self-correction and error detection, enhancing device performance and yield by identifying and repairing defects during fabrication.^16–19

Biomaterials, such as lipid membranes, polysaccharides, proteins, and nucleic acids, are derived from various natural living species, including microorganisms, plants, and animals.^20–22 These biomolecules (Fig. 1) can then be engineered to form templates for constructing miniature structures with precise control.^23,24 For example, carbohydrates, such as alginate, create hydrogel matrices that are ideal for immobilizing electronic components.^25,26 Moreover, proteins, like silk, can be processed into films or scaffolds to support electronic device fabrication.^27–30 Furthermore, nucleic acids, including DNA and RNA, are being investigated as building blocks for electronic devices, with potential applications in biosensors and computing, due to their unique properties in self-assembly and conductivity.^6,31,32

Fig. 1 Typical biological materials are used as templates for nanoelectronics assembly.

DNA is a highly adaptable biomaterial for engineering, offering numerous advantages in electronic device fabrication, including high-density storage and low energy consumption.^33–35 DNA's programmable nature, achieved through customized base pairing, facilitates the creation of uniform, reproducible, and stable structures, which allows for the development of intricate devices with nanoscale precision.^36–38 Furthermore, DNA's inherent biocompatibility makes it well-suited for biomedical electronics applications.^39,40 These essential characteristics position DNA as an appealing template material for electronic devices.⁶

Structural DNA nanotechnology offers the ability to create complex nanoscale shapes and patterns for templating nanoelectronics.^36,41 Among various techniques, DNA origami is particularly powerful due to its high customizability and ease of design.^42,43 DNA origami uses many short “staple” ssDNA strands to fold a long scaffold strand into nearly unlimited arbitrary geometries,^42,44 and inorganic materials can be attached to these structures to impart electrical functionality.^45,46 As a nanofabrication template, DNA origami has applications in a broad range of fields, and particularly in nanoelectronic devices with both precise dimensions and specific functionalities.^35,47Table 1 summarizes the major classes of biomaterials discussed in this review, highlighting their electronic applications and distinguishing characteristics. Table 2 summarizes different DNA assembly strategies for bioelectronic device nanofabrication.

Table 1 Overview of biomaterials used as templates in nanoelectronics: applications and functional characteristics

Biomaterial	Examples	Applications in electronics	Relevant descriptions
Viruses	M13, P22, TMV, CCMV	Templates for nanowires, sensors, optoelectronic devices, solar cells, biosensors	Self-assembling and genetically modifiable; high reproducibility; suitable for complex architectures
Bacteria	Engineered bacterial proteins	Conductive nanowires, biofilm-based switches, microbial fuel cells, pressure sensors	Biocompatible and self-healing; capable of adaptation; conductivity limitations addressed through engineering
Carbohydrates	Alginate, cellulose, chitosan	Sensors, biosensing devices, electronic detection, information storage platforms	Environmentally friendly; chemically versatile; functionalization and formation of nanoporous structures
Proteins and peptides	Silk, collagen, designed peptides	Nanopores, memory devices, sensors, field-effect transistors, logic gates	Sequence-tunable properties; support charge transport mechanisms; biodegradable; tunable for electronic functions
Lipids	Phospholipid nanodiscs	Flexible and printed electronics, dielectric layers, optoelectronic nanostructures	Amphipathic structures enabling membrane integration; stimuli-responsive sensing; thin dielectric films
Nucleic acids	DNA, RNA	Templating nanowires, metal–semiconductor junctions, nano-patterning, biosensors	Adaptable scaffolds for templating and self-assembly; biocompatible; conductive
DNA origami	DNA origami	Templating nanowires, metal–semiconductor junctions, nano-patterning, field-effect transistors	Highly programmable; precise; enable bottom-up assembly; metal and semiconducting nanostructures

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Table 2 Overview of DNA-templated nanoelectronics

Extended DNA electronics
Approach	Materials	Dominant interactions	Ref.
Ion seeding	Cu, Ag, Ni	Electrostatic	135–137
Contact association	SWCNTs	Electrostatic, π-stacking	138–141
Shadow lithography	Vapor deposition	Physical shape	145 and 146

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DNA origami templating
Seeding approach	Seed materials	Nanowire materials	Morphology	Site-specific	Ref.
Ionic	Pd, Ag, Pt	Au, Pd, Cu	Adequate	No	148,149 and 156
NP	Au	Au	Good	Yes	152–154,156 and 157
NR	Au, Te, CdS	Au, Te, CdS	Better	Yes	14,45 and 158–162

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In this review, we provide an overview of recent advances in the field of bio-templated nanoelectronics. We address bio-templates generally, including their structure, assembly, and functionalization with inorganic materials, before focusing on these features for DNA templates, with an emphasis on DNA origami. We divide the analysis of DNA origami nanoelectronic devices into two primary sections, first focusing on self-assembly methods, covering topics such as template morphology and substrate adhesion, and subsequently discussing electrical characterization. We intend to introduce the reader to bio-templated nanofabrication by covering the foundation of the technology, recent progress in the field, and future possibilities†.

Viruses

Viruses are the most abundant biological organisms in almost every ecosystem on earth.⁴⁸ Viruses have been explored as electronic assembly templates because of several important features. First, viral capsids provide highly ordered and reproducible nanoscale structures for precise positioning control.^49–52 Secondly, many viruses can be genetically engineered to introduce specific peptides or functional groups on the capsid, facilitating targeted material synthesis.^53,54 Thirdly, viruses naturally can self-assemble complex nanostructures.^50,55 This self-assembly is driven by a combination of noncovalent interactions, including electrostatic attraction, hydrogen bonding, hydrophobic effects, and van der Waals forces between capsid proteins. These interactions enable precise organization of viral components into ordered nanostructures, driven in many cases, by specific peptide sequences or surface charge distributions. Finally, viruses come in various shapes (e.g., spherical or rod-like), enabling diverse structures to be produced.^50,53 Employing viruses for the growth of hybrid organic–inorganic materials that possess self-repairing capabilities for electronic, magnetic, and catalytic systems is promising.^2,56,57 This approach offers significant advantages for precise self-assembly of electronic and magnetic devices in solar cells, batteries, energy storage, and medical diagnostics.^58–65

M13 bacteriophage is often used for the construction of phage display libraries due to its simple structure and ease of genetic manipulation.⁶⁶ The M13 genome can be easily modified, making it a useful template for self-assembly for the fabrication of nanoscale electronic components.⁶⁷ Belcher's team pioneered the use of M13 viruses in templating materials⁶⁸ and used M13 to recognize and bind to semiconductor materials, producing nanowires (NWs) and quantum dots.^53,69 Subsequently, genetically modified M13 was used as a framework scaffold in energy storage,^60,61,70,71 catalysis,^3,72 and biosensing.^73–75 Kim et al.^76,77 and Lee et al.⁷⁸ used a self-templating method on M13 to develop a multi-array colorimetric sensor for various chemicals. These sensors, optimized for complex environments through simulation and deep learning, could distinguish volatile organic compound mixtures and advance research in disease detection and contaminant identification. Han et al.⁷⁹ genetically modified M13 to generate specific amino acids to maximize templating and passivation for the growth of chalcogenide crystals and to produce a solar cell with an efficiency of 24% (Fig. 2a and b). Kim et al.⁸⁰ recently developed a flexible optoelectronic device with a plasmonic nanostructure by deposition of Au nanoparticles (NPs) on a genetically modified M13 phage template. This resulted in greatly increased interstitial plasmonic effects and localized surface plasmon resonance properties. These Au NP-M13 composites were integrated into the photoanode of fibrous dye-sensitized solar cells, and the hole injection layer of flexible organic light-emitting diodes achieved a 41% improvement in energy conversion efficiency and a 47% improvement in external quantum efficiency (Fig. 2c and d).

Fig. 2 Virus-templated electronics. (a) Perovskite solar cell device augmented by M13. (b) Wild-type M13 before genetic engineering. Reprinted from Han et al.⁷⁹ Copyright 2021 WILEY-VCH GmbH. (c) Flexible optoelectronic devices assembled using a genetically engineered M13 bacteriophage, with structure and schematic illustration of the direct anchoring process of Au plasmonic NPs onto the M13 bacteriophage, and novel gap-plasmon of the Au NP-M13 bio-nanostructure. (d) Bright-field TEM image of Au NP-M13 bio-nanostructure, and dark-field TEM images corresponding to elemental mapping. Reprinted from Kim et al.⁸⁰ Copyright 2024 WILEY-VCH GmbH. (e) Capacitive field-effect biosensor modified with a stacked bilayer of weak polyelectrolyte and plant virus particles as enzyme nanocarriers. Layer structure of the Al/p-Si/SiO₂/Ta₂O₅ sensor. (f) Schemes and corresponding TEM images of TMVCys-Bio particles deposited on carbon/Formvar-coated grids without (left) and with additional polycyclic aromatic hydrocarbon (right) surface layer. Reprinted from Welden et al.⁸⁷ Copyright 2023 Elsevier B.V.

Other viruses have also been researched as templates for the construction of nanomaterials. The bacteriophage P22 can form cage-like structures for the templating of electronics,⁸¹ and cowpea mosaic virus, with its icosahedral structure, is likewise suitable as a biotemplate.⁸² Cowpea chlorotic mottle virus and brome mosaic virus have further been used to create particles for templating electronic components.⁸³ Tobacco mosaic virus (TMV) with its rod-like structure is desirable for the production of NWs or other linear electronic components.^84,85 Welden et al.⁸⁶ developed a method for continuous detection of penicillin and urea using a modified field-effect electrolyte–insulator–semiconductor capacitor with enzyme nanocarriers immobilized on the surface of TMV. The TMV-supported dual-enzyme biosensor showed excellent sensitivity for urea and penicillin, which was achieved with a single p-Si–SiO₂–Ta₂O₅ sensor for multi-analyte detection. Welden et al.⁸⁷ further improved these biosensors by immobilizing penicillinase on TMV to create an antibiotic biosensor. They developed a modified biosensor by incorporating a TMV-based bilayer structure through layer-by-layer self-assembly, which enhanced enzyme immobilization and resulted in improved sensitivity to penicillin (Fig. 2e and f).

By harnessing programmable architectures and self-organization, viruses provide adaptable biological scaffolds for novel technologies and drive innovation in energy systems, light-responsive devices and biosensing through tailored material integration. However, although viruses are monodisperse and genetically tunable, they still have issues related to stability under diverse processing conditions, as well as biosafety issues. In addition, their dependence on aqueous environments limits compatibility with some microfabrication technologies.

Bacteria

Bacteria can also serve as templates for the assembly of electronic components and devices,⁸⁸ utilizing their distinctive properties to generate functional materials⁸⁹ and structures⁹⁰ for applications in electronics and energy storage.^91,92 This templating capability derives from cell surface features—outer membrane proteins and extracellular polymers—which facilitate the adsorption and nucleation of inorganic materials. Additionally, certain bacteria naturally express surface-localized redox-active proteins (e.g., cytochromes or nanowire-forming) that enable direct electron transfer to external materials. Assembling electronics using bacteria offers several advantages including biocompatibility, precise control, and adaptation to environmental changes.⁹³ However, challenges such as conductivity and stability also hinder the scaling up of production for practical applications.⁹⁴

Travaglini et al.⁸⁸ developed a method to integrate heme groups into gamma pre-folding protein (γPFD), originally produced by bacteria, creating conductive NWs (Fig. 3a) capable of electron transfer on the micrometer scale. These bacterial NWs exhibit enhanced electrical conductivity over short distances, functioning as power generators and respiratory sensors by harvesting energy from ambient humidity. Integrating heme (Fig. 3b) into protein scaffolds facilitates charge transfer through electron hopping between heme molecules, thereby enhancing current generation. Electrical characterization of γPFD filaments and γPFD-heme NWs was performed using conductive atomic force microscopy (c-AFM, Fig. 3c). A humidity-harvesting device incorporating a γPFD-heme NW film on a glass substrate generated significantly higher current and exhibited superior signal-to-noise ratios during successive relative humidity changes compared to devices made with γPFD filaments (Fig. 3d and e). This work demonstrates the potential of engineered bacterial protein-based materials for low-cost, self-contained electrical biosensors and bioelectronic devices.

Fig. 3 Bacteria-templated electronics. Structure of γPFD filaments and incorporation of heme to make conductive NWs. (a) Filament assembly of γPFD through β-sheet domains, and (b) proposed binding of heme molecules to the coiled-coil domains to form γPFD-heme NWs. (c) Electrical characterization of individual γPFD-heme NWs using c-AFM. AFM image and scheme of I–V measurements performed along the 3D morphology of a γPFD-heme NW that is in contact at one end with a gold electrode. The positions along the NW and gold electrode where I–V measurements were performed with the AFM tip are shown by crossed circles. (d) Design of a γPFD-heme NW-based humidity harvesting device and proposed electronic/protonic transport mechanisms. (e) Photograph of a fabricated humidity harvesting device that contains a γPFD-heme NW film. Reprinted from Travaglini et al.⁸⁸ Copyright Wiley-VCH GmbH 2024.

Chen et al.⁸⁹ used synthetic genetic circuits and cellular communication to regulate the production of Aspergillus amyloid filaments. These filaments were then combined with inorganic materials, such as quantum dots and Au NPs, and to create environmentally responsive biofilm-based electron switches, Au NWs and nanorods (NRs), and fluorescent quantum dot composites. Cao et al.⁹⁰ created hybrid organic–inorganic dome structures by applying Au NPs to bacterial communities. The dynamics of the dome structure in response to pressure were determined by its geometry, which could be easily modified by changing membrane properties. These resettable pressure sensors capable of signal processing based on different pressure levels and durations demonstrated the potential of this approach for diverse material fabrication applications. Wang et al.⁹² improved microbial fuel cell performance by genetically engineering Bacillus terrestris, a sulfur-reducing bacterium, to overexpress NW proteins that are critical for electron transfer. B. terrestris was modified to enhance NW protein production, and the engineered strains generated higher voltage output, increased power density, and improved normalized power output compared to unmodified controls. Overexpression also improved biofilm formation and electrical activity at the electrode. These findings suggest that increasing the abundance of NW proteins is an effective strategy to improve the electrical performance of Geobacillus-based fuel cells.

Bacteria offer modular platforms for dynamic bioelectronics and adaptive energy solutions. They thus enable scalable, responsive systems for sensing, energy generation and pressure-dependent technologies. While bacteria have advantages such as adaptability and biocompatibility, their inherently low electrical conductivity and time-dependent morphological variability—such as changes in shape, size, and growth patterns influenced by environmental conditions—can lead to inconsistent structural templates and poor device reproducibility. In addition, engineering challenges exist in maintaining bacterial viability and structural integrity throughout device fabrication.

Carbohydrates

Carbohydrates, including monosaccharides, oligosaccharides, and polysaccharides, serve as templates for the construction of devices with applications in electronic detection,⁹⁵ sensor preparation,⁹⁶ micro-transmission,⁹⁷ and biosensing.⁹⁸ Carbohydrates offer several advantages when used as templates for constructing electronic devices, particularly in the realm of environmentally sustainable and high specificity applications, making them a promising area of research and development in biosensing.⁹⁹ Along with these advantages, the structural complexity and stability of carbohydrates pose challenges, relative to more robust synthetic polymers and inorganic materials.¹⁰⁰

Carbohydrates can serve as building blocks for the assembly of electronic materials through functionalization with azido or amino groups to create functional materials^101–103 or stimuli-responsive surfactants.^104–107 In addition, carbohydrates allow synthesis of nanoporous supramolecules with potential applications in drug delivery, sensing, or information storage.^108–110 Leveraging inherent molecular versatility and environmental compatibility, carbohydrates enable customizable scaffolds for creating bioelectronics by translating tunable chemical modifications into adaptive sensing platforms or modular nanostructures. Although they are both environmentally friendly and chemically flexible, carbohydrates have low mechanical and thermal stability, and their high structural complexity and heterogeneity can lead to difficulties in high-resolution patterning and uniform electronic behavior.

Proteins and peptides

Protein and peptide-based nanomaterials offer great biocompatibility and established synthetic routes.¹¹¹ The wide variety of amino acid sequences enables the design of peptides and proteins with specific functional nanostructures for bioelectronic device assembly.¹¹² Inherent conduction mechanisms, such as tunneling and hopping, which are crucial for charge transfer in bioelectronics, can be influenced by sequence.¹¹³ The amino acid sequence can also affect stability, biodegradability, and proton transfer—key factors for developing sustainable electronic materials.^114,115 Peptide sequences can further be engineered to bind to specific materials, allowing for programmable NP assemblies that enhance the functionality of electronic components.¹¹⁶ One reported example used a modular zwitterionic peptide system to respond to SARS-CoV-2 protease activity by switching charge and inducing Au NP aggregation for visual detection through color change.¹¹⁷

Self-assembling peptides can form diverse nanostructures, including fibrils, tubes, and sheets, which can then serve as templates for organizing electronic materials.^{114,115,118–120} Engineered proteins can assemble metal NPs into designed structures, in applications like sensors, piezoelectric energy harvesters, and field-effect transistors, underscoring their versatility in electronics.¹²¹

Tian et al.¹²² demonstrated Au NP arrays with controlled spacing and orientation using computer-designed peptide templates. The cysteine residues in the peptide sequences provided binding sites for the Au NPs, resulting in the formation of nanotubes and nanoplates that organized the NPs into one- and two-dimensional structures (Fig. 4). This approach highlights the potential of computer-designed peptide assemblies for arranging inorganic nanomaterials. Bhullar et al.¹²³ developed a nanopore composed of 12 identical protein subunits with a channel length of 3.6 nm. This nanopore, equipped with valves, exhibited one-way passage properties and could be controlled by electrical potential, enabling directional control and three-step adjustable switching. The nanopore also remained stable across various pH and temperature conditions, with current flow demonstrating three distinct, reproducible steps corresponding to changes in channel size. This structure holds potential for disease diagnosis, as interactions between the nanopore and antigens reduced channel size by 32%, creating an analyte-responsive rectifier. Wang et al.¹²⁴ designed flexible, transient resistive memory devices using proteins and graphene quantum dots as active layers. These devices demonstrated write-once, read-many storage characteristics, with the quantum dots enhancing the switching current ratio. The devices also performed “OR” logic gate operations through sensitivity to ultraviolet light. Additionally, the active layer was biodegradable, dissolving entirely in deionized water within 20 min, making the devices promising candidates for transient electronic systems.

Fig. 4 Peptide-templated nanoelectronics. Sequence and self-assembly morphology model of Cyspeptide. Peptides assemble into homotetrameric coiled coils as building blocks for the further assembly of (a) nanotubes in pH 4.5 conditions and (b) two-dimensional plates in pH 7 conditions. Reprinted from Tian et al.¹²² Copyright ACS 2018.

Through sequence-defined architecture and molecular precision, protein and peptide nanomaterials are advantageous for adaptive bioelectronics. They combine programmable charge transport dynamics with environmental resilience to advance transient, logic-enabled systems while addressing scalability and operational lifetime. Despite these advantages, challenges remain in achieving precise control over the electronic properties of protein and peptide-based nanomaterials, as well as in ensuring long-term stability for practical applications.¹¹² Current research is focused on optimizing design, improving assembly, and enhancing electronic functionality.¹¹³ Further advances in controlling both the macrostructure and self-assembling building blocks will enable the creation of more sophisticated biomaterials for electronic applications.¹²¹

Lipids

Water-insoluble amphipathic lipids form the cell membrane, creating a stable barrier that hosts proteins responsible for selective transport, cellular recognition, energy storage, signaling, and compartmentalization.¹²⁵ The integration of lipid-based templates with nanomaterials offers advantages of biocompatibility and self-assembly, particularly for bioelectronics and optoelectronics.¹²⁶

Oertel et al.¹²⁷ presented a method for anisotropic metallization of phospholipid nanodiscs (NDs) via electroless gold deposition, enabling the growth of Au NPs on the lipid headgroup (Fig. 5a). This process resulted in a notable increase in the ND core diameter without altering its original thickness. Infrared spectroscopy and surface-enhanced Raman scattering revealed structural changes in the metallized NDs, including lipid swelling and the formation of internal interstitial spaces. Sharma et al.¹²⁸ employed lipid NDs to encapsulate alkane linker-arm-modified Au NPs, forming a ring-like structure (Fig. 5b). As temperature increased and lipid ordering decreased, the NDs transitioned into lipid vesicles, while the encapsulated Au NPs aggregated into tightly packed string or ring structures, impeding the vesiculation process. The impact of alkane linker arm length on ND stability and Au NP aggregation was studied in terms of the size and surface spacing distribution of Au NP aggregates, which in turn affected the luminescent properties of the Au NPs.¹²⁸

Fig. 5 Lipid-templated nanoelectronics. (a) HR-TEM image of Au NDs. Reprinted from Oertel et al.¹²⁷ Copyright Springer 2016. (b) Simulation snapshot with a cross-sectional slice along the ND plane of the lipid ND with 37 encapsulated Au NPs modified with C12 tethers obtained after 1.5 μs simulation time at 288 K. Reprinted from Sharma et al.¹²⁸ Copyright ACS 2017.

The integration of lipid membranes with silicon chips has facilitated the advancement of flexible and printed electronics, including organic and thin-film transistors. Kenaan et al.¹²⁹ reported dielectric monolayers of engineered lipids supported on silicon. These lipid monolayers were stabilized through a two-stage reticulation process, targeting both their aliphatic chains and head groups. With a thickness of less than 3 nm, these layers demonstrated low leakage currents and high dielectric robustness, positioning them as promising candidates for ultrathin dielectric applications in electronic devices.

Lipid architectures exploit dynamic molecular self-assembly and interfacial adaptability to bridge the gap between biological and nanomaterial systems. They offer tailored routes for ultrathin, biofunctionalized electronics and stimuli-responsive sensing, but require sophisticated engineering to balance stability and functional reproducibility. While lipid templates show great potential, challenges remain in achieving consistent performance and stability,¹³⁰ including vesicle fusion on solid supports and lipid polymerization.¹³¹ Further research is needed to optimize these systems for practical use in electronics applications.

DNA

DNA is the fundamental encoding molecule of genetic information for most organisms.¹³² Connected to DNA's information storage capabilities are its highly useful structural properties,¹³³ and DNA base pairing has been central to synthesis frameworks and designed structures since Seeman's initial work in 1982.³³

In the Woolley lab, we have used both double-stranded (ds) and single-stranded (ss) DNA as the structural basis for nanofabrication for over two decades. In 2001, we described a method for the controlled alignment of ssDNA on a surface (Fig. 6a).¹³⁴ We showed that controlling surface charge, decreasing intermolecular base pairing through solution composition, and translating the DNA solution across a surface with appropriate velocity allowed reliable deposition of DNA. For DNA elongation, precise control of the surface modifying poly-L-lysine concentration resulted in a balance between the forces binding the DNA to the surface and stretching it with a moving droplet. This method deposited aligned DNA that was used to template the formation of copper and silver NWs. Silver NWs (Fig. 6b) were created via the deposition of silver cations onto the negatively charged ssDNA with a solution of silver nitrate, followed by silver ion photoreduction to create silver metal on the DNA.¹³⁵ A similar procedure was used to create copper NWs (Fig. 6c), wherein copper(II) was associated with DNA and subsequently reduced with an ascorbic acid solution.¹³⁶ Nickel NWs (Fig. 6d) were likewise created on surface DNA using a solution of nickel chloride or nitrate in ethanol to associate nickel(II) with deposited DNA, followed by reduction to nickel metal NWs, used as is to specifically place histidine-tagged proteins.¹³⁷

Fig. 6 Images of DNA templates and metal deposition. (a) Tapping mode AFM height image of a segment of a λ ssDNA molecule on mica (height scale is 1.0 nm). Reprinted from Woolley et al.¹³⁴ Copyright 2001 ACS. (b) DNA on silicon that has been treated with AgNO₃ has an increased height, as well as a more granular appearance, indicating areas of metal deposition. Reprinted from Monson et al.¹³⁵ Copyright 2002 AIP. (c) λ DNA deposited on silicon and treated with copper(II) nitrate followed by ascorbic acid; regions where Cu has deposited (see arrows) have an increased height (scale is 5.0 nm). Reprinted from Monson et al.¹³⁶ Copyright 2003 ACS. (d) Linear nickel metal nanostructures made on surface DNA. Reprinted from Becerril et al.¹³⁷ Copyright 2006 ACS. (e) λ-DNA-templated SWCNT positioning on Si surfaces; white arrow indicates SWCNTs (height scale is 4.0 nm). Reprinted from Xin et al.¹³⁸ Copyright 2003 ACS. (f) DNA-templated SWCNT positioning using a surfactant-wrapped SWCNT suspension (height scale is 5.0 nm). Reprinted from Xin et al.¹³⁹ Copyright 2005 IOP. (g) DNA-templated SWCNT on top of and bridging electrodes. Reprinted from Xin et al.¹⁴⁰ Copyright 2006 AIP. (h) A pair of ssDNA molecules on a microfabricated substrate after a silver metallization treatment. Reprinted from Becerril et al.¹⁴² Copyright 2004 AIP. TEM images of DNA-templated metallization of branched structures with (i) silver or (j) copper. Reprinted from Becerril et al.¹⁴³ Copyright 2005 ACS. (k) SEM images of Bi₂Te₃ NWs obtained after immersing DNA-templated Ni NWs into a solution consisting of 0.01 M HTeO₂⁺, 0.01 M Bi₃⁺ and 1 M HNO₃ for 2 h at room temperature. Reprinted from Liu et al.¹⁴⁴ Copyright 2013 ACS. (l) DNA shadow nanolithography. Reprinted from Becerril et al.¹⁴⁵ Copyright 2007 Wiley-VCH Verlag.

In parallel work for creating conductive nanostructures, our lab localized single walled carbon nanotubes (SWCNTs) on DNA. Pyrene methylamine (PMA) was used to treat SWCNTs; PMA interacts electrostatically with the negatively charged DNA via its amine group and further interacts with the SWCNTs (Fig. 6e) via π–π stacking.¹³⁸ To improve SWCNT localization efficiency, our lab subsequently treated SWCNTs with surfactant to facilitate association to DNA, increasing the percentage of SWCNTs attached to the DNA (Fig. 6f).¹³⁹ SWCNTs prepared in this way were further electrically characterized by aligning them on a substrate that had been previously patterned with electrodes (Fig. 6g), with linear current vs. voltage plots showing resistance on the order of 10⁶ Ohms.¹⁴⁰ SWCNTs and DNA remain an important area of research, and significant breakthroughs have been made recently in the fabrication of nanotube field effect transistors using DNA patterns.¹⁴¹

Our lab further developed a method for indexing and locating specific DNA-templated materials on a substrate using micromachining. This technique was used to study the differences in silver NW (Fig. 6h) measurement by AFM and SEM.¹⁴² We also designed and created complex structures including branched DNA. Using seeding and reduction methods, our lab metallized three-arm branched DNA structures with both silver (Fig. 6i) and copper (Fig. 6j).¹⁴³ To expand the possibility of DNA templated nanoelectronics to include semiconductor materials, we evaluated galvanic displacement to create semiconductor NWs templated on DNA.¹⁴⁴ Initially, Ni NWs were formed on extended λ DNA molecules using the typical seeding and plating method. After creating these wires, they were covered with solution containing Bi³⁺ and/or HTeO₂, which underwent a redox reaction galvanically displacing the nickel and depositing tellurium or bismuth telluride (Fig. 6k).

An alternative method for patterning from DNA was developed that uses the physical presence of DNA to block the deposition of metal vapor on the surface. This process, called DNA shadow nanolithography (Fig. 6l), uses thermal evaporation on an angled substrate so that the metal source is not directly perpendicular to it, creating a deposition “shadow” behind the raised DNA structures. The metal film is then used as a mask to specifically etch the substrate below; this approach provided high-resolution patterning, at the level of optical lithography at the time.¹⁴⁵ More recently, others have developed patterning with DNA or DNA origami as a mask for lithographic processes. Liu's group¹⁴⁶ devised a method for selective atomic layer deposition of metal oxides on DNA nanostructures deposited on polystyrene. The DNA nanostructures acted as templates to selectively initiate the growth of metal oxides, which could be used as hard masks for further patterning applications.

DNA origami

In 2006, a technique called “DNA origami” emerged as a powerful tool for nanofabrication and self-assembly.⁴² In DNA origami a long “scaffold strand” DNA substrate is folded over itself looping back and forth to fill a designed 2-dimensional shape. The scaffold strand is then locked in place with the addition of hundreds of “staple” strands that hold adjacent sections of the folded scaffold together through hybridization, such that the design of these staple strands determines the shape of the final DNA origami structure. DNA origami can further be made using elongated staple strands to create targeted areas for hybridization-based attachment. Supporting this approach, an open-source software program named caDNAno was developed by Douglas et al.¹⁴⁷ for design of complex, custom nanostructures in three dimensions.

The development of DNA origami allowed for the creation of custom-designed and complex DNA templated NWs and junctions. In 2011, we used DNA origami to form branched gold nanostructures.¹⁴⁸ T-shaped DNA origami nanostructures were formed and deposited on surfaces, anchored with Mg²⁺ in the deposition solution. The surface DNA was seeded with silver ions in solution before treatment with a commercial gold electroless plating solution. This procedure successfully created tri branched gold structures (Fig. 7a), which were continuous but primarily composed of bulbous grains that often overlapped with each other.

Fig. 7 DNA origami metallization and interaction with NPs. (a) SEM of branched DNA origami after Ag seeding and Au plating; reprinted from Liu et al.¹⁴⁸ Copyright 2011 ACS. (b) SEM of Pd NWs on mica; reprinted from Geng et al.¹⁴⁹ Copyright 2011 RSC. (c) SEM of Cu-metallized DNA origami structures interfaced with Au electrodes for electrical measurements; reprinted from Geng et al.¹⁵¹ Copyright 2013 ACS. (d) SEM of Au NP seeds on “T” DNA origami after treatment with plating solution; reprinted from Pearson et al.¹⁵² Copyright 2012 ACS. (e) Process schematic showing DNA origami attachment using BCP micelle patterning and (f) AFM data of DNA origami bridging between Au NPs; reprinted from Pearson et al.¹⁵⁶ Copyright 2011 ACS.

Another method for the metallization of DNA was investigated that used palladium as a seeding ion, and both gold and palladium NWs were successfully created on a mica substrate (Fig. 7b).¹⁴⁹ We used both λ DNA and DNA origami as substrates for the NW seeding process and found that DNA attachment to the surface was improved by a preliminary treatment with Mg²⁺. Magnesium treatment also improved the consistency and continuity of seeded NWs; the seeded DNA was plated with an electroless plating solution of either palladium or gold to create the final NWs. Recently, the Keller group¹⁵⁰ thoroughly analyzed the thermal stability of DNA origami nanostructures in aqueous solutions containing different concentrations of Mg²⁺. They found that the measured melting temperatures of the DNA origami nanostructures deviated significantly from the melting temperatures calculated from the DNA sequence, especially under high ionic strength conditions. This suggests that the thermal stability of DNA origami under high ionic strength conditions is influenced by mechanical stresses in addition to electrostatic interactions.

The techniques developed for the metallization of DNA were transferred from mica supports to patterned silicon substrates. This allowed for more straightforward electrical characterization of the plated structures that could be synthesized spanning pairs of microscopic electrodes.¹⁵¹ Plating materials of gold and copper were used for high electrical conductivity (Fig. 7c). We observed Ohmic behavior of these nanomaterials; however, the resistivity was about 4 orders of magnitude greater than for bulk copper, and about 3 orders of magnitude higher for gold.

Another common way to pattern nanomaterials using DNA is the placement or alignment of nanomaterials onto DNA structures, a method that the Woolley lab has used extensively. Nanomaterials, either NPs or NRs, are functionalized with a surface coating, such as an ionic surfactant that associates electrostatically with the DNA, or polynucleotides that selectively hybridize to complementary sequences. We used Au NPs functionalized with poly T ssDNA to localize NPs on specific areas of a DNA origami substrate (Fig. 7d).¹⁵² Selected staple strands in the DNA origami were extended having a complementary poly A sequence that selectively bound the functionalized NPs. With subsequent electroless plating, continuous conductive metal nanostructures were created; as with ionic seeding, the NPs clustered, resulting in variations in NW diameter. One potential solution to this is to space out the NPs and make the seeding density more uniform. To allow for more precise control in structures, the Finkelstein group¹⁵³ seeded Au NPs on the corners of a rectangular DNA origami to show site-specific deposition. We decreased the number of attachment sites on the DNA origami substrate, so Au NPs were successfully spaced more.¹⁵⁴ This can potentially increase the likelihood of gaps between NPs, impacting the ability to form continuous NWs. However, by carefully controlling the time for hybridization and the concentrations of Mg²⁺, DNA, and NPs, we optimized the procedure to minimize gap size as well as the number of nonspecifically localized NPs. This process allows nanomaterial arrangement on DNA origami with practical applications in biomarker detection. For example, Sharma et al.¹⁵⁵ designed a DNA origami-based system that assembles Au NR dimers to create plasmonic hotspots for surface-enhanced Raman detection of a cancer-related protein, demonstrating potential for diagnostics.

One challenge in the creation of useful DNA nanomaterials from the bottom up is the placement of these materials at specific locations on a substrate, because DNA origami is typically deposited randomly. As one solution to this issue, we revised the technique of NPs seeding for NW synthesis and instead localized DNA on a substrate with fixed Au NPs.¹⁵⁶ Au NPs were formed using a block copolymer (BCP) shell that allowed them to self-assemble into a regular array. After removing the BCP and functionalizing the NPs with poly-T DNA, DNA origami with poly-A staple strands on each end selectively bound to separate NPs (Fig. 7e and f). This BCP patterning created DNA origami attachment sites well matched to the size scale of the DNA template, which was crucial for precise nanoscale surface patterning.

Because of the spatial selectivity of the NP seeding method, it can be used to deposit multiple metals. We used this to seed Au NPs on one portion of a DNA origami, and after plating the Au to create a continuous NW, it was reacted with octadecanethiol, which protected the deposited gold during subsequent processes. Ionic seeding with platinum was then plated with copper on the other side of the structure (Fig. 8a) to create a heterometallic junction.¹⁵⁷ The gold deposition was highly specific and consistent, but the copper deposition was less regular, and morphology was more challenging to control.

Fig. 8 DNA origami-templated NWs and heterojunctions. (a) Process used for making Au–Cu junctions on DNA origami. Reprinted from Uprety et al.¹⁵⁷ Copyright 2014 ACS. (b) Anisotropic electroless plating on DNA origami to form conductive NWs. Reprinted from Uprety et al.¹⁵⁸ Copyright 2017 ACS. (c) Process for site-specific metallization of DNA origami using DNA-functionalized Au NRs. Reprinted from Uprety et al.¹⁴ Copyright 2017 ACS. (d) Four-point electrical measurements on DNA origami-templated Au NWs. Reprinted from Aryal et al.¹⁵⁹ Copyright 2018 ACS. (e) SEM images of site-specific binding of Au and Te NRs on DNA origami with EBID wiring. Reprinted from Aryal et al.⁴⁵ Copyright 2020 Springer. (f) SEM images of Au–Te contacts formed by polymer-encased annealing. Reprinted from Aryal et al.¹⁶¹ Copyright 2021 ACS. (g) Schematic of DNA-templated Au−CdS heterojunction assembly/characterization and (h) SEM images of Au−CdS heterojunctions with EBID tungsten connections and representative I–V curves; reprinted from Pang et al.¹⁶² Copyright 2024 ACS.

While plating on Au NPs is generally isotropic, using NRs instead of spherical NPs can allow plating to proceed anisotropically. We thus developed a method for NW synthesis using localized NRs on DNA origami.¹⁵⁸ This procedure, while similar to that used for NPs, also requires tighter control of conditions to ensure anisotropic growth of the NRs (Fig. 8b). The most significant difference was the introduction of cetyltrimethylammonium bromide, an ionic surfactant that slows the growth of NPs, promoting growth anisotropy when combined with a small amount of silver ions in solution and HCl that slowed the reduction of gold by ascorbic acid. This process produced thin, continuous NWs with lower resistivity than nearly all previously reported DNA-templated NWs.

The directional specificity of NR growth, combined with the orientational and positional selectivity of DNA origami binding, create a powerful method for the synthesis of conductive nanostructures of varied geometries. Using rectangle-shaped DNA origami with localized sticky-end staple strands, Au NRs were associated in specific orientations on the DNA. To position the NRs, they were functionalized with poly-T DNA as for NP seeding. Au NR patterns were assembled on the DNA and made contiguous through electroless Au deposition (Fig. 8c).¹⁴ This method was further developed to template additional Au nanostructure shapes; C-shaped Au NWs were electrically characterized using four-point I–V measurement. The DNA templates were deposited on an oxidized silicon surface patterned with gold pads for probe station contact. The nanomaterials were electrically connected to the gold pads via platinum probes created using electron beam induced deposition (EBID). These nanostructures showed Ohmic behavior (Fig. 8d),¹⁵⁹ though with higher resistivity than previously measured NWs.

We used a similar method with DNA nanotubes to create Au NWs with lengths approaching the micrometer scale. DNA nanotubes are constructed from multiple DNA blocks that modularly assemble into a cylindrical lattice, allowing the nanotubes to be extended to arbitrary lengths that are convenient for the templating of NWs. Both gold NRs and palladium ions were used to seed DNA nanotubes before plating. The NWs seeded with NRs were narrower, had a more consistent diameter, and had less background deposition.¹⁶⁰ The NWs exhibited similar resistivities to those templated with other forms of DNA origami.

Building on extensive work with DNA-templated conductive NWs, we utilized this foundation for DNA-templated creation of metal–semiconductor contacts.⁴⁵ Using a linear DNA origami template with periodic segments containing staple strands modified with sticky-end sequences, Au NRs bearing the complementary sequence were localized on the template. After removing the DNA from the surface of the Au NRs, surfactant-wrapped Te NRs were successfully localized in the gaps between Au NRs (Fig. 8e). Using electroless plating, the Au NRs were extended to create electrical connections to Te NRs. Structures were characterized by I–V measurement following processes developed for Au NWs. Importantly, the metal–semiconductor contacts exhibited nonlinear I–V curves indicative of non-Ohmic, Schottky-like behavior, although overall current through junctions was low.

Because not all anticipated nanodevice architectures can be connected using electroless deposition of gold, a different method of forming nanoscale electrical connections was developed using polymer encasing and annealing.¹⁶¹ After associating Au and Te NRs with a DNA template, the surface was coated with a thin polymer layer. The nanostructures were then annealed, which permitted the gold to migrate to contact Te, with larger morphological changes being restricted by the polymer (Fig. 8f). Optimal annealing temperatures occurred around 170 °C, with lower temperatures showing no material movement and higher temperatures resulting in Au NR deformation. This method resulted in metal–semiconductor contacts with similar electrical characteristics to those created by electroless plating. We recently interfaced CdS NRs with Au NRs to create heterojunctions with improved electrical properties (Fig. 8g).¹⁶² Metal–semiconductor contacts were formed through electroless deposition of Au. These Au–CdS junctions exhibited similar I–V curves to Au–Te junctions, but had much higher conductance values, up to 1.7 × 10⁻⁴ S (Fig. 8h).¹⁶²

Additionally, other groups have made progress in creating DNA templated metal nanostructures. Arce et al.¹⁶³ used techniques pioneered by the Siedel group to create approximately cylindrical, electrically conductive Au NWs using DNA origami molds. DNA origami with site-specific localization were used by Song et al.¹⁶⁴ to create chiral Au nano helices with unique plasmonic and optical properties. Larger scale frameworks of metal and semiconductor materials were further templated by Michelson et al.¹⁶⁵ using DNA origami.

The programmable molecular architecture of DNA and its sequence-controlled assembly enable precision-manufactured systems at the nanoscale that show promise for hybrid electronics by integrating conductive and semiconductive elements. At the intersection of DNA nanotechnology, materials science, and device engineering, the strategies outlined here provide a roadmap for designing programmable nanoscale architectures with tailored material and electrical properties. This approach offers a glimpse at possibilities for future biomolecule-integrated systems in next-generation electronics.

This section on DNA as a structural and functional template for nanoelectronics has been written following more than two decades of foundational work in the Woolley group. We recognize that our efforts have been enabled through synergistic contributions from many researchers and acknowledge the strong, collaborative research community driving the development of bio-templated and especially DNA-templated nanoelectronics.

Outlook

Looking ahead, the field of bio-templated nanoelectronics has much to offer through programmable structure and nanoscale precision, enabling the simultaneous creation of conductive scaffolds, molecular recognition elements, and spatial organizers for functional components within a single integrated system.^35,41,47 Virus-based templates, and particularly the related DNA origami, are likely to play a key role in the development of customizable nanoelectronic devices. Advances in design will further enable the precise control of biomolecular templates and enhance their ability to self-assemble complex structures for applications in biosensing,^{76,77,86,87,123,155} information storage,^{33–36,108–110} and medical diagnostics.^61,63,65,124

Future breakthroughs are anticipated for in situ fabrication, dynamic reconfigurability, and bio-electronic interfacing, enabled by advances in computational design, machine learning-guided self-assembly, and real-time nanoscale characterization.^{76,77,147,148} The development of standardized toolkits for the design and self-assembly of biomaterials along with automated manufacturing processes has promise to bridge the gap between laboratory-scale demonstration and commercial production.^21,43,129 Emerging emphases in neuromorphic computing, wearable electronics, and quantum devices will be facilitated by the programmability, biocompatibility, and positional precision of biomolecular templates.^114,115,125

However, significant challenges remain to be overcome. Thermodynamically driven self-assembly processes must be optimized in terms of yield and timescale. Moreover, the stability of biotemplated components under thermal, chemical or mechanical stress needs to be enhanced.^113,130,131 Additionally, integration with conventional semiconductor devices should be improved through control of surface chemistry.^146,151 Futhermore, variability between batches will need to decrease for manufacturing to be both scalable and reproducible.^20,21,31 Finally, standardized metrics for benchmarking performance against traditional approaches will require development.^38,45,159 Addressing these challenges will afford new opportunities in creating hybrid systems that combine the desirable properties of biomolecules with the robustness of conventional inorganic materials. In addition, optimizing biocompatibility will open new possibilities for biomedical electronics, including wearable sensors, bio-computing and implantable devices.

In the future, bio-templated nanoelectronics may further impact fields from renewable energy and environmental sensing to next-generation computing and medical technologies. Interdisciplinary collaboration will be critical to realize the full potential of such systems, drawing together expertise from molecular biology, physics, chemistry, materials science, electrical engineering, computer programming, medicine, etc.^1,5,8,42,43 As synthetic biology, AI-assisted design, and materials science converge, bio-templated nanoelectronics may transition from complementing traditional fabrication methods to becoming the approach of choice, ushering in a new era of programmable, sustainable, and intelligent materials.^21,123 Indeed, bio-templated nanoelectronics have potential to redefine the way we approach nanofabrication, with their precision, sustainability and functionality driving innovation.

AI disclosure statement

This work was supported by AI technologies, including ChatGPT, DeepSeek, InstaText and Grammarly, which refined the language, improved clarity and transformed the content into standardized academic English. DeepL Translate facilitated translation tasks, while SciSpace, LitMap and Connected Papers helped with literature searches, displaying scientific connections and contextualizing research topics. AI technology also played a role in synthesizing technical content, ensuring thematic coherence between sections, preserving the authors’ scientific intent, and reducing redundancy through adaptive rephrasing and structural refinement.

Conflicts of interest

The authors declare no competing financial interest.

Data availability

No primary research results, software or code have been included and no new data were generated or analysed as part of this review.

Acknowledgements

We acknowledge support from the BYU Department of Chemistry and Biochemistry for a postdoctoral research fellowship to C. P. We thank the BYU College of Computational, Mathematical, and Physical Sciences for an Undergraduate Research Award to B. T. K.

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Footnote

† Portions of the Introduction have been adapted from Chao Pang's doctoral dissertation, DNA-Templated Nanofabrication of Metal–Semiconductor Heterojunctions and Their Electrical Characterization, Brigham Young University, 2024.

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