Periodic Reporting for period 1 - VERITASCAN (The cold-chain challenge: à la carte Time-temperature indicators enabled by patterned structural colour in organic semiconductors)
Reporting period: 2023-02-01 to 2024-07-31
The problem: How does one verify that perishable pharmaceutical and medical products have been stored at appropriate temperatures until they reach the patient? Electronic temperature loggers appear to offer a straightforward solution for the wholesalers. However, this cold-chain control measure becomes prohibitively expensive for the myriad of second-tier distributors who handle individual packages – and even more so for the end-users who may handle an individual ampule. In 2014 an estimated 15% of temperature-sensitive pharmaceuticals, which commonly require storage at 2–8 ºC, were discarded worldwide. However, it was the COVID-19 pandemic that fully exposed the scope of the cold-chain challenge. The most widely used vaccines based on messenger ribonucleic acid (mRNA) explicitly require storage at –70 ºC (Pfizer-BioNTech) or –20 ºC (Moderna) to avoid hydrolysis and loss of potency. Besides the obvious economic and environmental impact of discarded drugs, unconscious administration of ineffectual, thermally degraded vaccines results in undesirable side-effects, with a disastrous cost to human lives.
The standard means of verifying cold-chain handling are thaw- or, more generally, time-temperature indicators (TTI). These devices are designed to indicate partial thermal history, providing an irreversible visual signal above a threshold temperature. However, adapting the TTIs used in the food industry for the pharmaceutical market has proven ineffective due to the distinct key performance indicators demanded by the end-users. TTIs require small size and flexible form factors to suit various packaging formats, intuitive readability, low production cost, and time-temperature response.
The solution: We propose a new class of TTIs based on patterned and thermally erasable structural colour in organic semiconductors (OSCs). Why is this preferable for TTI design over the familiar compositional colour? Unlike the latter, structural colour in these materials does not spontaneously bleach but can be erased on-demand by controllable diffusion of a molecular ‘solvent’ activated by its melting at a predetermined temperature. In other words, information written with structural colour within our proposed device concept can be erased or modified when the temperature goes above the target threshold. Our vision is to deliver TTIs featuring temperature-responsive QR codes and provide the end-user directly with the ultimate cold chain authentication: veracity that can be scanned. The concept harnesses Arrhenius-type diffusion characteristics that optimally reflect accumulated thermal exposure, while OSCs inherently feature flexible form factors and ultra-low fabrication costs for solution-processed thin films.
The standard means of verifying cold-chain handling are thaw- or, more generally, time-temperature indicators (TTI). These devices are designed to indicate partial thermal history, providing an irreversible visual signal above a threshold temperature. However, adapting the TTIs used in the food industry for the pharmaceutical market has proven ineffective due to the distinct key performance indicators demanded by the end-users. TTIs require small size and flexible form factors to suit various packaging formats, intuitive readability, low production cost, and time-temperature response.
The solution: We propose a new class of TTIs based on patterned and thermally erasable structural colour in organic semiconductors (OSCs). Why is this preferable for TTI design over the familiar compositional colour? Unlike the latter, structural colour in these materials does not spontaneously bleach but can be erased on-demand by controllable diffusion of a molecular ‘solvent’ activated by its melting at a predetermined temperature. In other words, information written with structural colour within our proposed device concept can be erased or modified when the temperature goes above the target threshold. Our vision is to deliver TTIs featuring temperature-responsive QR codes and provide the end-user directly with the ultimate cold chain authentication: veracity that can be scanned. The concept harnesses Arrhenius-type diffusion characteristics that optimally reflect accumulated thermal exposure, while OSCs inherently feature flexible form factors and ultra-low fabrication costs for solution-processed thin films.
In the framework of VERITASCAN, the team has validated the concept of TTI based on erasable structural colour by producing a large number of samples of three basic prototypes. The basic structure of the devices consists of three layers, namely, a small molecular solvent which melting temperature is set to the critical temperature for the given application (e.g. 8 ºC for medicines that requires a fridge), an interlayer that prevents undesired activation of the device, and a semiconductor layer with strong colour shifting properties. When the ambient temperature increases above the critical temperature, the solvent melts and diffuses through the interlayer reaching the semiconductor and thus changing its color.
Prototype I responds to the need of having a very simple TTI in which a Yes/No answer is provided to the question: has this product made temperature excursions that make it unsafe to use? Besides the commercial value for specific markets of this prototype, the simplicity of the device architecture enabled us to make a very large screening of materials and processing parameters. Indeed, more than 25 different solvents, 6 semiconductor systems, 6 types of interlayers, and four types of substrates (glass, plastic, paper and aluminium foil) were investigated. This broad study helped to identify the best materials in terms of cost, processability and non-toxicity. In the second prototype, the semiconducting layer was pre-structured to include a given image, such as QR code, or an OK symbol. Following the same process, excursions above the critical temperature erase the printed image. Type III prototype delivers a more precise time indication and is of use for applications in which the accumulated time above the critical temperature needs to be recorded. In order to avoid the need to store the TTIs themselves at low temperatures, three activation mechanisms have also been investigated, lamination using PET, lamination using gel, and the use of a solvent reservoir blister which distributes the solvent upon applying pressure.
To improve readability and trust on the TTIs, we have also developed a software that can analyse a picture of the device and inform the user of the time that the product has exceeded the critical temperature. Finally, based on the software capabilities, we have devised a fourth prototype in which, for the first time in the power-free TTIs development, time and temperature can be independently determined. The mathematical framework to analyse dual TTIs with different architectures has been advanced.
Prototype I responds to the need of having a very simple TTI in which a Yes/No answer is provided to the question: has this product made temperature excursions that make it unsafe to use? Besides the commercial value for specific markets of this prototype, the simplicity of the device architecture enabled us to make a very large screening of materials and processing parameters. Indeed, more than 25 different solvents, 6 semiconductor systems, 6 types of interlayers, and four types of substrates (glass, plastic, paper and aluminium foil) were investigated. This broad study helped to identify the best materials in terms of cost, processability and non-toxicity. In the second prototype, the semiconducting layer was pre-structured to include a given image, such as QR code, or an OK symbol. Following the same process, excursions above the critical temperature erase the printed image. Type III prototype delivers a more precise time indication and is of use for applications in which the accumulated time above the critical temperature needs to be recorded. In order to avoid the need to store the TTIs themselves at low temperatures, three activation mechanisms have also been investigated, lamination using PET, lamination using gel, and the use of a solvent reservoir blister which distributes the solvent upon applying pressure.
To improve readability and trust on the TTIs, we have also developed a software that can analyse a picture of the device and inform the user of the time that the product has exceeded the critical temperature. Finally, based on the software capabilities, we have devised a fourth prototype in which, for the first time in the power-free TTIs development, time and temperature can be independently determined. The mathematical framework to analyse dual TTIs with different architectures has been advanced.
The advanced prototypes and two-way reading method go beyond the state of the art in several ways:
1) Broadest operational range in the market: most commercially available TTIs can only address one critical temperature and a particular time window. VERITASCAN technology is a fully customizable platform that can be designed for threshold temperatures spanning from – 16 ºC to 60 ºC (already demonstrated) and potentially liquid nitrogen temperatures. Equally, the time window can be tuned on demand, from seconds to weeks (already demonstrated). This is a current market need, according to pharma and logistics end-users.
2) The use of structural colour helps the stability of the device (no colour bleaching over time), and allows an easy contrast optimization.
3) Much thinner and lightweight than the existing TTIs. Being a printed device, scalability is easily achieved on different substrates (glass, plastic, paper, foil), yielding a very thin planar device.
4) Advanced device reading method based on a piece of software (which will result in the near future in an app for a mobile phone) that analyse a photograph of the device and increases user confidence in the result, which is a current bottleneck for the wider deployment of TTIs as identified by end-users.
5) Technological breakthrough introduced by being able to simultaneously determine at which temperature and for how long was a monitored product taken to. This is a unique feature for a non-electronic TTI, as it bridges the sensing capabilities of an optical TTI and brings them closer to what an electronic data-logger monitors, but without the need of a battery.
All of these advantages have made us work to file a patent on the concept, device implementations, and method of reading it. The conversations already held with potential end-users have already identified potential clients. So, following the created business plan canvas, VERITASCAN next steps will include negotiating and partnering with strong industrial players in order to scale up the technology, as well as secure funding from private investors and public calls such as EIC Transition.
1) Broadest operational range in the market: most commercially available TTIs can only address one critical temperature and a particular time window. VERITASCAN technology is a fully customizable platform that can be designed for threshold temperatures spanning from – 16 ºC to 60 ºC (already demonstrated) and potentially liquid nitrogen temperatures. Equally, the time window can be tuned on demand, from seconds to weeks (already demonstrated). This is a current market need, according to pharma and logistics end-users.
2) The use of structural colour helps the stability of the device (no colour bleaching over time), and allows an easy contrast optimization.
3) Much thinner and lightweight than the existing TTIs. Being a printed device, scalability is easily achieved on different substrates (glass, plastic, paper, foil), yielding a very thin planar device.
4) Advanced device reading method based on a piece of software (which will result in the near future in an app for a mobile phone) that analyse a photograph of the device and increases user confidence in the result, which is a current bottleneck for the wider deployment of TTIs as identified by end-users.
5) Technological breakthrough introduced by being able to simultaneously determine at which temperature and for how long was a monitored product taken to. This is a unique feature for a non-electronic TTI, as it bridges the sensing capabilities of an optical TTI and brings them closer to what an electronic data-logger monitors, but without the need of a battery.
All of these advantages have made us work to file a patent on the concept, device implementations, and method of reading it. The conversations already held with potential end-users have already identified potential clients. So, following the created business plan canvas, VERITASCAN next steps will include negotiating and partnering with strong industrial players in order to scale up the technology, as well as secure funding from private investors and public calls such as EIC Transition.