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Safe and Ingestible Fluorescent Silk Tags Authenticate Drugs | BioScan | photonics textbook

To help block the flow of counterfeit drugs, researchers from Purdue University and South Korea’s National Institute of Agricultural Sciences have developed edible fluorescent tags that can be coded and added to pills or liquid medications. Each label is made from natural photoluminescent biopolymers and contains an imperceptible matrix code of information about the pharmaceutical product. The code can be read with a smartphone app.

The opportunity for the development stems from supply chain issues and the rise in the number and popularity of online pharmacies, which have facilitated the introduction of counterfeit versions of drugs and medicines into the market.

Although fluorescent synthetic materials are already available for use as tracking codes, the substances they are made from are potentially dangerous to consume.

In search of an edible, safe and durable material that could be placed directly on drugs and made fluorescent, researchers turned to silk. They genetically modified silkworms to produce silk fibroins – edible proteins that give silk fibers their strength – with a cyan, green or red fluorescent protein attached. They then dissolved the fluorescent silk fibroins to create fluorescent polymer solutions, which they applied to a thin film of white silk 9 mm wide placed on a square grid. When the researchers shone violet-blue, blue, and green light onto the grid, square 3D patterns in cyan, green, and red appeared, respectively.

The researchers then developed a fabrication method to generate imperceptible, multidimensional matrix codes that could be used to encrypt information in a manner similar to conventional barcodes or QR codes. Genetically encoded silk fibroin was used as the material for the matrix codes.


Silkworms can produce edible, fluorescent silk cocoons (left side of left image). Cocoon proteins can be used in edible codes (right) to verify the authenticity of drugs. Courtesy of AEC Core Sciences2022, DOI: 10.1021/acscentsci.1c01233.


Edible codes can be read on a smartphone by placing optical filters on the phone’s camera. An application designed by the researchers is used to scan the fluorescent pattern and extract a digitized security key augmented by a deep neural network to overcome code patterns erroneously formed during manufacturing, and a cryptographic hash function for enhanced security .

To reliably extract a digitized key from the edible matrix code, the researchers used a 2D convolutional neural network that takes raw fluorescence images of the input code and returns a binary output key of each color of fluorescence emission. .

After establishing the cryptographic key extraction protocol, the researchers used a smartphone to demonstrate authentication at the dose of an oral drug in a simulated setting. To test the fluorescent code’s ability to work with alcohol-based liquid medications, the researchers placed a coded silk film in a whiskey bottle and found that the fluorescent code was still readable with the app.

The study of the digestibility of the proposed edible codes showed that fluorescent silk proteins are broken down by gastrointestinal enzymes. To ensure that the edible code can support anti-counterfeiting measures and assay-level authentication functions, they characterized the code’s biocompatibility, photostability, thermal stability, and long-term reliability.

An edible code affixed to individual doses of medications could serve as serialization, track and trace, and dosage-level authentication, allowing each patient to play a part in preventing the payment of fake pharmaceuticals. Proposed all-protein-based matrix codes for single-dose drugs could also help patients and caregivers prevent unintended use of counterfeit drugs.

In a hospital pharmacy, the edible code could also be used to create unit packs and unit dose packs to reduce the risk of dispensing errors. The researchers also believe the edible code could potentially be used for other security and cryptography applications that require erasure immediately after being scanned.

The research has been published in AEC Core Sciences (www.doi.org/10.1021/acscentsci.1c01233).