Nanoscale Dog Printing: DNA Origami Meets Lithography

Welcome everyone!

What’s better than DNA nanotech? Combining DNA nanotech with traditional nanotechnology techniques to get the best of both worlds! In this issue, we explore how researchers mixed DNA origami and lithography, to create nanocrystals patterns! Including a smiley and a dog!

Let’s dive right in.

Dog Prints in DNA: DNA Origami Lattices Mix with Lithography

Nanotech: the Heart of Technology

Electronics powers almost everything: from your phone, to the GPU in your laptop, to the screen in your smart fridge (was that really necessary?). And do you know what is at the core of all of these devices? Nanotechnology: chips can be created with components on the scale of just a few nanometers, using techniques like lithography, etching and vapor deposition.

These top-down techniques are powerful and are great at creating 2D shapes with nanometer-scale resolution, but:

• 3D patterning is difficult and requires complex and expensive processes.

• Precise positioning of molecules like proteins or nanoparticles is nearly impossible, because these tools can’t “grab” and place objects at the molecular scale.

• Molecular-level customization (like spacing ligands or enzymes at specific spacing) is out of reach with conventional inorganic fabrication.

But you know what is great at all this? DNA origami.

The Molecular Precision of DNA Origami

DNA origami creates 2D or 3D nanoscale structures using a long, single stranded DNA “scaffold” that is folded into shape using shorter single stranded “staples”. DNA origami offers:

• Bottom-up self assembly with nanoscale precisions

• Programmable binding sites for nanoparticles or proteins at exact locations.

• 3D architectures that are impossible to build with top-down methods.

• Biocompatibility, making it ideal for integrating with biological systems (much better than silicon-based tools!)

In short, DNA origami gives you molecular-level construction tools. The problem? Combining the two worlds of top-down techniques with bottom-up DNA self assembly.

Designing DNA Origami Frameworks

This is the problem the authors of today’s paper (you can read it here!) set out to solve. Their focus: DNA origami frameworks. These are 3D lattices made by connecting octahedral DNA frames using DNA sticky ends at their vertices.

The team designed two complementary octahedral frames, called OA and OB, that self-assemble to form cubic superlattices, growing into crystals as large as 20 μm. That’s a lot of DNA!

The synthesis of DNA framework works great in solution, but their controlled growth on surfaces is challenging. And this is important for the creation of devices with various applications: from cell-targeting scaffolds to molecular electronics!

Top-Down Meets Bottom-Up: Electron Beam Lithography

So, after creating the DNA frameworks the team needed a 2D surface to stick them onto. To create it, they turned to electron-beam lithography to define arrays of PEG hydrogel microwells, 20-100 μm in diameter. These wells act as the “landing zones” for the DNA frames. But this begs the question: what is lithography?

What is Lithography?

Okay so, I am no expert in “traditional” nanotech techniques. And for everyone in the same shoes, here is a small intro to electron beam lithography (EBL). Nanotech experts, fell free to skip this!

EBL is a high-resolution variant of lithography. This technique can be used to sculpt patterns with extremely fine features, down to a few nanometers, on surfaces like silicon or glass.

Okay, so how does EBL work?

1. Coating: A substrate is coated with an electron-sensitive material called a resist.

2. Exposure: A focused beam of electrons “draws” patterns onto the resist, inducing the PEG polymerization

3. Development: The resist is washed, removing unexposed regions

4. (Optional) Processing: The exposed areas can be etched or filled with materials to build nanoscale structures

EBL directly writes pattern with ultra-high resolution (<10 nm). Unfortunately, it’s also slow and expensive. EBL is ideal for prototyping or creating templates (like in this case), but it’s not great for mass production.

From Patterns to Crystals: Growing DNA Frameworks

Okay, once the patterned PEG surface was ready, the researchers added a mixture of OA and OB frames. A slow thermal annealing promotes crystal growth, to obtain the DNA frameworks inside the microwells!

The researchers controlled different aspects of the frameworks’ assembly by playing with some parameters:

• Crystal orientation and symmetry were controlled by using either OA only or OA+OB as seed layers.

• Nucleation density varied with the hydrophilicity of the surface (fresher, more hydrophilic surfaces worked better).

• Crystal growth rate and size could be tuned by changing the diameter of the microwells.

DNA Origami Patterns: Logos, Smiley Faces and Dogs

But they didn’t stop here. The team demonstrated this technique by creating functional nano-patterns in the shape of:

• A smiley face

• The Brookhaven National Laboratory logo

• And even a cute dog!

But it wasn’t just for show. These patterned lattices weren’t empty, but they carried functional cargo:

• Gold nanoparticles (AuNPs) attached via DNA strands

• Fluorescent proteins (Alexa488-labeled streptavidin)

These patterns serve as proof-of-concept for potential real-world applications.

Why? Real-World Applications

This demonstrate potential for applications:

• Biomedical engineering: The biocompatibility of this system can help create DNA-protein frameworks patterns to guide cell adhesion and growth for engineered tissues. Another possibility is to create DNA frameworks loaded with drugs on implantable surfaces!

• Information Storage and Nanoelectronics: Patterned DNA frameworks can work as molecular barcodes, carrying sequence-encoded information readable by fluorescence. Or maybe the DNA origami frameworks could wire nanoparticles or metals to create 3D circuits!

• Sensing Metasurfaces: Embedding silver or gold nanoparticles at specific places in lattices can create very sensitive surfaces, useful for any kind of sensing.

Conclusions

Such a cool paper! This work enables large-area, programmable assembly of DNA nanostructures into 3D lattices with:

• Micrometer precision,

• Orientation control,

• Tunable domain size, and

• Functional cargo loading.

This work bridges top-down nanofabrication with bottom-up DNA self-assembly, and it offers a scalable way to integrate DNA-based material in real-world devices. This is such a cool space! I would love to know more, so if you have some suggestions for me, please reply to this email and tell me! So, cool work: go and read it for yourself here!

If you made it this far, thank you! Until next time!

More Room:

• Nanodrill, baby, Nanodrill: Who cares about targeted delivery? Just drill, baby. This study introduces a programmable DNA origami nanodrill that can attach to and penetrate cell membranes, causing mechanical disruption and inducing cancer cell death. The nanodrill forms transmembrane channels that raise intracellular calcium and trigger protein release. A pH-responsive design enables acid-triggered activation, allowing controlled, targeted cytotoxicity. Everyone’s dream drug!

• More DNA Octahedrons: In the unlikely case you didn’t have enough of DNA octahedron, I have the paper for you. This study introduces a highly sensitive ECL biosensor for detecting m6A-RNA, a key cancer marker. Using a 3D DNA octahedron for enhanced target capture and AuAg nanoclusters for signal amplification, the sensor achieves high specificity and a(n insane) detection limit of 140 aM, offering strong potential for early cancer diagnosis.

• Targeted Drug Delivery, Again: No, we are not done with mRNA delivery. This study proposes lipid transition temperature (Tm) as a key factor for rational design of lipid nanoparticles (LNPs) used in mRNA delivery. While the ionizable lipid H7T4 showed good physical properties, it performed poorly alone. However, combining it with a low-Tm helper lipid like DOPE improved mRNA uptake in vitro and in vivo. The results show that tuning Tm can enhance LNP efficiency, offering a more systematic approach to helper lipid selection.

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