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A glass stamp reproduces precise, nanometer-scale etchings in silver. This original engraving is 10 microns wide - less than a quarter of the diameter of a human hair. Credit: Kyle Jacobs; MIT

The days of having vials of blood drawn for diagnostic testing could become history if lab-on-a-chip technology develops to its full potential. LOCs are a specialized type of micro-electro-mechanical system device, comprising an array of tiny diagnostic sensors. For example, LOCs may be able to detect early stage cancer cells from a single drop of blood. Other applications of LOCs include immunoassays, biochemical assays, polymerase chain reactions (used for DNA sequencing) and more. Besides reducing blood-draw-dread, LOCs could be of great service to health care providers in regions that lack medical supplies and laboratory equipment.

To fully realize the advantages of these applications, manufacturing of LOCs needs to be affordable and reproducible. Existing fabrication methods such as electron beam lithography and nanoimprint technology have the disadvantages of being (respectively) expensive and imprecise. A new approach that uses a glass stamp to replicate patterns on a substrate shows promise as a cost-effective way to make high-resolution patterns, which is a key step in fabricating LOCs.

A group at MIT published a paper in Nanotechnology describing the use of superionic silver metaphosphate glasses to “stamp” precise, nanoscale patterns on silver substrates. Inspired by glassblowers and noting that molten glass can be molded quickly and smoothly, Professor Nicholas Fang says in a press release with regard to glass molding, “it works very well at a small scale, too, at a very high speed.”

The glass Fang studied, AgI-AgPO₃, is a solid electrolyte and has a high room temperature ionic conductivity, where Ag+ is the mobile ion. Particles of the low-melting composition were melted in a small syringe at less than 200°C, and pressed onto a metallic master pattern to create a glass stamp.

Patterns were “stamped” by pressing the glass stamp against a silver substrate and applying a voltage above the silver layer. The voltage stimulated ions in both the glass and silver surfaces, causing the glass mold pattern to effectively etch into the silver surface. The group reports that patterns in a variety of geometric features were stamped with resolutions of 30 nm and etch rates of up to 20 nm per second.

The metallic master pattern still must be made using expensive lithographic techniques, but glass stamps may open the door to cost effective mass-production of LOCs. Fang notes in the press release that only one master pattern and one glass stamp are needed to produce an entire line of sensors. The paper’s abstract also notes that the glass has enough transparency to overlay and integrate with existing fabrication tooling. Fang says, “With this stamp, I can reproduce maybe tens of hundreds of these sensors, and each of them will be almost identical.”

For full details, see “Solid-state superionic stamping with silver iodide-silver metaphosphate glass,” K. E. Jacobs et al., Nanotechnology (doi:10.1088/0957-4484/22/42/425301)

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Microneedles fabricated with two-photon polymerization:
Credit: Royal Society of Chemistry

I first covered ACerS member Roger Narayan’s work in the field of two-photon polymerization a little more than a year ago in a story for ACerS’ membership magazine, the Bulletin. For several years, Narayan, a professor in the Joint Biomedical Engineering Department that is connected with NC State’s College of Engineering and the University of North Carolina at Chapel Hill, has been examining the use of this rapid prototyping approach using ceramic–polymer hybrid materials to create patient-specific microscale medical prostheses, scaffolds for tissue engineering and microscale medical devices.

One of set of applications he has been working on, in particular, is using two-photon polymerization to create arrays of fine microneedles. (Conceptually, Narayan’s polymerization process is like a 3D ink jet process that builds up structures on the nanoscale.)

Recently, Narayan coauthored a paper on the novel use of microneedles to deliver quantum dots into the skin. “Our findings are significant, in part, because this technology will potentially enable researchers to deliver quantum dots, suspended in solution, to deeper layers of skin. That could be useful for the diagnosis and treatment of skin cancers, among other conditions,” Narayan says in a news release from NCSU.

QDs, sometimes called “artificial atoms,” are semiconductor materials that fall into the category of nanocrystals, and they contain a variable number of electrons that occupy well-defined, discrete quantum states.

This groups is attracted to the use of QDs because of their ability to serve as fluorophores and also work as drug delivery vehicles. QD-based fluorescent probes can be engineered to be superior to organic dye fluorophore by being brighter and having better photostability (can fluoresce after one hour of continuous excitation), signal-to-noise ratio, emission ranges and fluorescent lifetimes. Researchers report they can use their intense fluorescence to track individual molecules.

Sample quantum dot with bio coating. Credit: Histesh R. Patel

At this point, Narayan and the other researchers just are using the microneedles on pig skin and can capture images of the quantum dots entering the skin using multiphoton microscopy. Although this work is still preliminary, these images allow the researchers to verify the basic effectiveness of the microneedles as a delivery mechanism for quantum dots.

The hope is that multiphoton microscopy will have clinical applications using real-time imaging materials such as the quantum dots for faster diagnosis of cancers or other medical problems.

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