Safety and Security

At the heart of our InkSight project lies the commitment to safety and security of our team, the public, and the environment. This innovative technology involves engineering mammalian cells to act as sensors within a hydrogel matrix in order to change tattoo contrast upon biomarker detection. Introducing an engineered living system into a diagnostic application presents unique biosafety, biocontainment, and ethical considerations. Given the distinctive nature of this tattoo system, we have adopted a multi-layered safety approach, that is built upon three fundamental pillars: General Lab Safety to protect our team and our surroundings according to established standards, Conceptual Safety embedded in the design of InkSight itself, and Regulatory Safety to ensure responsible innovation within existing and future governance approaches.

Conceptual Safety

This chapter shows how safety is inherent in our design approach of each component, exemplified in our choice of non-pathogenic mammalian cells, secure encapsulation within a robust hydrogel matrix, and the inclusion of a reliable genetic kill-switch as a primary biocontainment measure.

Regulatory Safety

To ensure responsible innovation, this chapter explores the governance framework surrounding our technology, evaluating its dual-use potential, biosafety containment measures, and addressing core social and ethical questions regarding the future of InkSight.

General Lab Safety

This chapter provides a thorough overview of the strict safety standards that protect our team and guide our every day work, covering essential training, laboratory and institutional rules, and critical operational procedures for waste disposal and electrical device handling.

Conceptual Safety

From its inception, the biosafety of our engineered mammalian cell system has been a priority in the development of InkSight. We have intentionally designed every component, from genetic circuit elements to material encapsulation, to maximize biosecurity and ensure robust biocontainment. This commitment drove an iterative design process in which we created, researched, and tested multiple safety strategies, including kill-switch mechanisms, hydrogel entrapment, and melanin encapsulation. Together, these features confine biological components within a stable, inert matrix, embedding biosafety directly into the material and genetic architecture of InkSight.

Melanin Encapsulation

Melanins are ubiquitous biological pigments with diverse protective functions, from UV shielding to stress resistance. Our work focuses on eumelanin, the brown-black form that determines skin tone. Its biosynthesis begins with the amino acid tyrosine, and the critical initial steps are catalyzed by tyrosinases, copper-dependent enzymes that generate highly reactive quinone intermediates. While melanin itself can be benign, these synthesis intermediates are cytotoxic and mutagenic, posing a significant biosafety challenge for engineered systems (Guo et al., 2023).

In nature, mammals solve this problem through specialized melanosomes: complex, membrane-bound organelles within melanocytes that safely confine the entire melanogenesis process (Graham et al., 1978), (Raposo and Marks, 2007). We drew inspiration from this compartmentalization strategy and thus worked with a synthetic, orthogonal solution (Cichorek et al., 2013).

Our engineered safety solution is a synthetic melanosome. We utilize self-assembling encapsulin nanocages to create dedicated reaction vessels (Sigmund et al., 2018). By localizing tyrosinases to the interior of these protein shells, we spatially confine melanin production and sequestration. This design effectively mimics the protective function of natural melanosomes, shielding the cellular machinery from harmful intermediates and allowing for the safe accumulation of pigment at high concentrations. This compartmentalization is central to InkSight’s design, ensuring that melanin production occurs without compromising cellular viability. Learn more about melanin in our Project Description!

The technology’s efficacy is contingent on achieving sufficient contrast against the natural skin background, which may be limited in individuals with darker skin tones due to higher basal melanin levels. We acknowledge that this physiological variation could potentially create disparities in InkSight´s functionality and accessibility. Therefore, our ongoing pigment research focuses on engineering solutions that enhance accessibility and effectiveness across diverse skin tones.

Kill-Switch

The development of a fail-safe mechanism, or “kill-switch”, was guided by our responsibility to prioritize patient safety. It follows direct reccomendations and request to implement this safety mechanism, as shown in the results of our survey. This idea was reinforced when we talked to several experts, as well as informal conversations in scientific events.

Conventional termination strategies, such as temperature shifts or nutrient deprivation, are imprecise and often unsuitable for dynamic biological systems, like mammalian cells. In line with iGEM’s emphasis on genetic safeguards, we explored systems that integrate a synthetic genetic circuit at their core. Such approaches allow precise and rapid control over cell viability by activating intrinsic pathways like apoptosis through inducible regulators. These engineered “kill switches” serve as reliable safety mechanisms, enabling the targeted and timely elimination of engineered cells in complex biological environments.

Our design implements the established inducible Caspase 9 (iCas9) system (Di Stasi et al., 2011), widely recognized for its high robustness and specificity in therapeutic applications, as demonstrated in foundational literature like the publication of Ramos et al. (2010) and previous iGEM projects like iGEM Munich 2023’s BEE and iGEM AFCM Egypt 2024’s Song-H.

The iCasp9 construct encodes a chimeric protein composed of a modified human FK506-binding protein (FKBP12-F36V), sometimes termed diemrisation domain B, fused to a truncated, activation-domain-deficient caspase 9 (ΔCASP9). Upon administration, a bivalent cell-permeable drug, typically AP1903 (Rimiducid) or AP20187 (B/B homodimerizer), binds with high affinity to the engineered FKBP domains, inducing rapid homodimerization. This forced proximity triggers auto-proteolytic cleavage and activation of the caspase 9 moiety. The activated iCasp9 subsequentially initiates an irreversible proteolytic cascade by cleaving downstream effector caspases (e.g., caspase 3), culminating in rapid apoptosis (Yuan et al., 2022).

Unlike other kill switches that rely on leaky expression to keep host viability, iCasp9 activation depends on an externally administered, non-therapeutic molecule AP20187, allowing high level of control over the “kill-switch”. Additionally, as the mechanism utilizes a human-derived apoptotic pathway, it minimizes immunogenic risk compared to bacterial or viral systems. A single low-dose (10 nM) application is sufficient to eliminate over 95% of transduced cells (Ramos et al., 2010), fulfilling our main safety criteria of specificity, rapid effectiveness, and pharmacological reliability.

To rigorously validate the functionality and efficiency of our iCasp9 kill-switch system, we designed a comprehensive experimental protocol. Cloning was already been conducted successfully, and experiments are ongoing these weeks to fully experimentally validate our constructs.

Hydrogel

The genetic circuit implemented in our engineered mammalian cells contains non-endogenous components. These could trigger immune responses upon implantation in the dermis, leading to inflammation and the accumulation of immune cells around the cell patch. Encapsulation within a hydrogel therefore serves as a protective barrier to mitigate such reactions and adds a safety measure by preventing cell migration into surrounding tissue. In contrast, multiple hydrogels are already in medical use and classified as non-immunogenic (Zhang et al., 2019).

Therefore, from a regulatory perspective, hydrogel encapsulation is also a prerequisite for any future consideration of clinical application. In the European Union, and in Germany in particular, the use of hydrogels falls uder Medical Device Regulation (MDR). Containment strategies such as hydrogel encapsulation are regarded as essential safeguards for biosafety. Without them, approval processes by authorities such as European Medicines Agency (EMA) or the Paul-Ehrlich-Institut would not be feasible. Learn more under our Regulatory Safety!

Thus, beyond scientific necessity, the hydrogel forms a regulatory requirement to translate such technology into practice. The initial conceptualization of the tattoo system did not prioritize hydrogel encapsulation. This perspective evolved significantly through a critical analysis of existing literature and expert consultation, leading to a refined set of design criteria.

The pivotal insight came from reviewing the work of Dr. Tastanova (Tastanova et al., 2018). Her cellular tattoo, employing exclusively endogenous genetic elements, demonstrated that hydrogel encapsulation was not a universal requirement for biocompatibility. However, our use of non-endogenous components immediately established hydrogel encapsulation as an indispensable biosafety and containment strategy. Furthermore, her work revealed a critical functional constraint: the hydrogel used was insufficiently transparent for naked-eye detection, establishing optical clarity as a non-negotiable parameter beyond mere biocompatibility. As we learned in subsequent meetings, that list of requirements would grow to be very extensive.

Further input came from Prof. Lieleg, who emphasized that mechanical performance of the gel had been underestimated. He stressed that covalent crosslinking is likely essential to maintain stability in vivo over several weeks or months. However, common approaches such as photo-activated crosslinking involve potential risks, including harmful radical concentrations or light doses compromising cell viability. There have been advances in hydrogel crosslinking technologies which are completely radical free. As shown by Rizzo et al. (2023), these could provide a more suitable solution. As a practical path forward, he suggested beginning with relatively simple gelatin- or alginate-based systems in order to test for transparency first, then gradually increasing crosslinking density and re-evaluating. Yet, he also cautioned that such simple systems may ultimately fall short of the required optical clarity.

Through these discussions, the criteria for an ideal hydrogel were refined and ranked:

1. Biocompatibility (minimal immunogenicity)
2. Transparency (sufficient for optical readout of pigmentation)
3. Porosity (adequate for molecular diffusion, though not considered the main bottleneck)
4. Stability (weeks to months in tissue)
5. Gelation kinetics (injectable pre-gel, crosslinking in vivo)
6. Tunability (control over crosslink density and mechanics)

Based on these requirements, a literature review was undertaken to identify hydrogel systems with potential beyond the simple starting points. Systems employing bioorthogonal click chemistry and self-healing dynamic covalent networks were identified as promising candidates for future development. Eventually, we have identified two promsing systems: the Hyaluronic Acid–PEG Click Hydrogel (SPAAC Crosslinked) and the Collagen–PEG Thiol–Maleimide Hydrogel.

Hyaluronic Acid–PEG Click Hydrogel (SPAAC Crosslinked) A promising candidate for our application is a hydrogel formed by crosslinking hyaluronic acid (HA) with polyethylene glycol (PEG) using strain-promoted azide-alkyne cycloaddition (SPAAC). This system was initially developed by Fu et al. (2017) as an advanced dermal filler, highlighting its inherent suitability for intradermal implantation. The gelation process involves chemically modifying HA with cyclooctyne moieties and mixing it with azide-terminated multi-arm PEG. The key advantage of this SPAAC “click” chemistry is that crosslinking begins immediately upon mixing under physiological conditions. This mechanism is highly attractive for our purposes: No photo-activation, avoiding potential light-induced cytotoxicity. No toxic catalysts (e.g., copper), minimizing the risk of harmful byproducts that could compromise encapsulated cell viability. Hyaluronic acid itself has an excellent clinical track record and is widely approved by regulatory agencies (FDA, EMA) in dermal fillers (e.g., Monovisc, Cingal) (Clegg et al., 2024). However, it is critical to note that these approved products use different crosslinking strategies (e.g., with biscarbodiimide). To our knowledge, there are no SPAAC-crosslinked HA hydrogel currently approved for clinical use.

Collagen–PEG Thiol–Maleimide Hydrogel A second candidate system is a hydrogel formed by crosslinking type I collagen with polyethylene glycol (PEG) via a thiol-maleimide reaction. This specific formulation was developed by Rosenquist et al. (2023) for ealing corneal lesions. A highly sensitive application that demands excellent biocompatibility and transparency. The gelation process involves modifying collagen to present free thiol groups, which are then mixed with maleimide-functionalized multi-arm PEG. The thiol-maleimide Michael addition is a rapid and efficient reaction, allowing for in-situ gelation upon mixing without requiring external triggers. This system has considerable advantages as well: Innate bioactivity of collagen provides natural cell-adhesion motifs to support encapsulated cell survival and function. Mechanical strength and tunability conveyed through PEG to create a robust, covalently crosslinked network. Collagen, like HA, is a well-established biomaterial with a long history of clinical use. Multiple collagen-based products are FDA- and EMA-approved for dermal and soft tissue applications (e.g., CosmoDerm) (Clegg et al., 2024).

Public Perception and Safety Integration

Understanding safety not only as a technical issue but also as a social and perceptual one was central to our approach. To complement expert consultations, we conducted a comprehensive online survey reaching 246 participants to explore how different publics perceive the safety of living biosensor tattoos. This survey revealed how safety is understood differently depending on personal experience with medical technologies, underscoring the importance of transparency and trust in biodesign. Using a Latent Class Analysis (LCA), we identified two main attitudinal groups: a larger segment skeptical of safety and a smaller group optimistic about it.

The prevalence of safety-related concerns in these findings directly shaped our design priorities described above, leading us to strengthen containment and, considerinng specific requests in the open-ended feedback, develop an inducible kill-switch mechanism. The full analysis and results are presented on our Human Practices section.

Regulatory Safety

The development of any powerful new technology carries a profound responsibility to anticipate and mitigate potential risks. Guided by the iGEM’s core principles of safe and responsible innovation, our team conducted a rigorous safety and security analysis for InkSight. This process combined internal deliberation, extensive consultation with professionals, and our comprehensive Policy Analysis, which explored governance, legislation, and socio-technical dimensions of safety. Together, these efforts helped us identify potential risks across human health, environmental spread, national security, and social equity.

In direct response, InkSight’s design is rooted in proactive safety-by-design, implementing robust biocontainment measures such as a biological kill-switch and physical encapsulation. The Policy Analysis further deepened this framework by addressing regulatory pathways, ethical reflection, and speculative futures for hybrid models bridging art and medicine. The full document can be explored below, alongside our Human Practices page. This document outlines our comprehensive approach to fulfil our ethical and governance-related obligations, demonstrating that responsible development is the foundation of our innovation. We invite you to read through this section as a summary of our Policy Analysis, where we cover all these topics in greater detail.

Regulatory Framework

Advanced Therapy Medicinal Products and EU Medical Device Regulation

Our project, InkSight, falls under the European Union’s regulatory framework for Advanced Therapy Medicinal Products (ATMPs). Although designed for diagnostic rather than therapeutic use, InkSight meets the legal definition of a somatic cell therapy medicinal product per Directive 2001/83/EC, which includes diagnostics via pharmacological or metabolic action.

Specifically, it would be regulated as combined ATMP, as it consists of engineered mammalian cells (the biological component) embedded within a hydrogel matrix (the medical device component):

• firstly, the device incorporates living cells that are themselves classified as an somatic cell therapy medicinal product under ATMP, and
• secondly, the hydrogel scaffold used for cell encapsulation is consistently treated as a long-term medical device implant in regulatory guidance due to their profound interaction with the human body.

As a combined ATMP, InkSight is subject to centralized evaluation by the European Medicines Agency (EMA) and must comply with both medicinal product regulations (e.g., Regulation ((EC) 1394/2007 European Union, 2007)) and medical device requirements (e.g., (EU MDR 2017/745 European Union, 2017)). This dual regulatory pathway ensures thorough and harmonized oversight across all member states, emphasizing our commitment to safety, efficacy, and compliance from an early developmental stage. Beyond its biological classification, the safety and efficacy of the InkSight system hinge on the performance of its physical hydrogel scaffold. This brings into focus the critical regulations for the hydrogel matrix under the EU’s medical device framework.

Here, The hydrogel matrix is independently regulated under the EU Medical Device Regulation (MDR 2017/745) as a Class III medical device, the highest risk category, due to its intended use and associated risks. Consequently, the hydrogel must undergo a rigorous conformity assessment process to demonstrate full compliance with the MDR’s essential requirements for safety, biological compatibility, sterility, and mechanical performance, ensuring the entire system meets the highest standards of patient safety.

Approval Pathways and Precedents

Once classified, navigating the centralized approval pathway requires careful planning and engagement with several regulatory bodies. The European Medicines Agency (EMA), through its Committee for Advanced Therapies (CAT), would oversee the centralized regulatory approval of InkSight as an Advanced Therapy Medicinal Product (ATMP). As a combined ATMP, InkSight would follow a structured pathway beginning with an optional (but highly advisable) request for formal product classification to obtain regulatory clarity. For an academic team like ours, applying for Small and Medium-Sized Enterprise (SME) status with the EMA is a critical first step, as it provides significant fee reductions, incentives, and regulatory guidance.

The approval process involves the parallel generation of extensive quality and non-clinical data for the biological component, which can be certified early by the CAT, and a conformity assessment of the hydrogel medical device component by a Notified Body. This Notified Body would evaluate the device under the MDR, including an audit of the Quality Management System (QMS) according to ISO 13485, and issue a CE certificate for the scaffold. All certificates and technical documentation from the device assessment are then integrated into the Marketing Authorisation Application (MAA) submitted to the EMA for final evaluation and approval. Facing a timeline of several years before a clinical trial can even begin, we are engaging in early dialogue with regulators and exploring flexible frameworks such as Germany’s Digital Health Applications (DiGA) Fast-Track model, enabling monitored pilot testing in Munich clinics to generate safety data and support responsible, accelerated innovation.

The emerging field of living biosensor tattoos is informed by key scientific precedents that highlight distinct regulatory pathways based on biological chassis. The work of Tastanova et al. (2018), using engineered human cells for subcutaneous biomarker detection, reinforces InkSight’s anticipated classification as a Combined ATMP. In contrast, systems employing non-human organisms, such as the bacterial-based tattoo developed by Allen et al. (2024), would be subject to alternative regulations governing genetically modified organisms and medical devices. Although neither precedent has yet entered formal regulatory review, both underscore the critical importance of early and deliberate safety-by-design — a principle central to InkSight’s development within the established ATMP framework.

Intellectual Property and Safety

While we decided not to pursue patenting within the iGEM framework due to limited time and resources, we recognize that intellectual property (IP) protection can play a crucial role beyond economic strategy. In this context, patenting is also a safeguard mechanism—it helps prevent unregulated imitation, misuse, or application for unintended purposes. By securing defined rights and oversight, responsible IP management can contribute to safety, accountability, and ethical stewardship in the development.

Biosecurity and Dual-Use

Life sciences research has driven tremendous global progress, yet also introduces a fundamental ethical tension: the same discoveries that benefit humanity could also be deliberately misused to cause significant harm. This challenge, known as the dual-use dilemma, is formally addressed in the context of Dual-Use Research of Concern (DURC) --- research that, while beneficial, could be directly misapplied to threaten public health, security, or the environment.

The regulatory landscape is still evolving, particularly in the EU, where the lack of a harmonized definition of “dual use” complicates consistent oversight. Although iGEM originates within a U.S. framework, our project, which was developed in Germany, requires a dual-use analysis that actively incorporates EU and German legal perspectives, ensuring our safety and security protocols align with regional expectations and emerging European policies, such as those outlined in the 2024 European Commission White Paper on dual-use technologies.

Biosecurity in the EU and in Germany

A significant regulatory gap exists in the voluntary nature of DNA synthesis screening, as there is no mandatory legal requirement for it in the EU or Germany. While most providers adhere to the International Gene Synthesis Consortium (IGSC)’s screening protocol, this self-regulated system remains vulnerable. To mitigate this risk, InkSight proactively sources all DNA exclusively from IGSC-member companies and subjects all genetic parts to iGEM’s safety review. We align our practices with emerging global efforts, such as the International Biosecurity and Biosafety Initiative for Science (IBBIS), which advocate for universal and enforceable screening standards to strengthen biosecurity in an increasingly accessible field of synthetic biology.

In Germany, biosecurity is governed by a robust regulatory framework including the Biological Agents Ordinance (BioStoffV) and the Infection Protection Act (IfSG)], with specialized agencies like the Robert Koch Institute (RKI) and the Federal Institute for Risk Assessment (BfR) providing expert oversight of biological materials and GMOs. Although Germany lacks specific legally binding statutes addressing Dual-Use Research of Concern (DURC), leading scientific bodies such as the Leopoldina and the Deutsche Forschungsgemeinschaft (DFG) have established ethical guidelines and codes of conduct that encourage researchers to critically evaluate the dual-use potential of their work. While not mandatory, these reflect a growing cultural and professional expectation for responsible science and self-regulation within the German research community.

Dual-Use Analysis

Research and development in the life sciences have been a cornerstone of modern progress, yet the very discoveries that offer profound benefits also carry an inherent risk of misuse, a challenge known as the “dual-use dilemma.” A specific category of this research, formally designated as Dual-Use Research of Concern, refers to work that could be directly misapplied to pose a significant threat to public health, safety, or the environment.

For our project, InkSight, which is conceived and executed in Germany, a thorough dual-use analysis must extend beyond U.S.-centric frameworks to incorporate the specific legal and ethical context of the European Union. Within the EU, DURC is addressed as a broad guiding principle integrated into existing institutional and legal frameworks, such as the Dual-Use Regulation (EU) (2021/821 European Union, 2021) and national biosafety laws, rather than as a specific legal designation with a dedicated assessment process. This approach, however, faces challenges, as highlighted by the European Commission’s 2024 White Paper, which notes that a persistent lack of a common EU-level definition for ‘dual use’ creates obstacles for consistent oversight.

In developing InkSight, we have proactively prioritized safety through intentional design choices to navigate this landscape. The system is fundamentally constrained by its use of non-pathogenic, encapsulated mammalian cells with limited survivability outside controlled settings, and it is intended solely for personal diagnostic use. To guarantee safe and ethical application, access will be restricted to licensed tattoo studios where practitioners must complete a specialized certification program, and every client will provide fully informed consent based on a detailed safety sheet.

However, we recognize that the technology’s potential for misuse lies not only in the biological material itself but perhaps more significantly in the unethical application of the knowledge it generates. Risks include non-consensual monitoring, such as covert testing by employers or insurers, as well as discriminatory tracking or reproductive coercion. In direct response to these possibilities, we advocate for strict ethical guidelines that prohibit surveillance or forensic uses, limit biomarker validation to clinically relevant contexts, and ensure that all communications emphasize a care-centered design philosophy. This comprehensive approach, combining technical containment with ethical foresight, forms our strategy for responsible innovation within the European context.

Biosafety and Containment

Our biosafety strategy employs a multi-layered “safety-by-design” approach. Engineered cells are physically contained using a semi-permeable hydrogel to prevent dispersal and maintain localized, safe melanin production. Additionally, we integrate a validated genetic kill-switch (iCasp9 system), enabling controlled, triggered cell elimination to address long-term persistence concerns. These features directly respond to technical risks and public feedback, ensuring safety at both biological and ethical levels.

InkSight’s production and use adhere to strict German and EU biosafety regulations. Cell line development follows Risk Group 1 (BSL-1) containment standards under the Biological Agents Ordinance (BioStoffV), with future clinical production requiring full Good Manufacturing Practice (GMP) compliance. The hydrogel scaffold must meet Medical Device Regulation (MDR) Class III and ISO 13485 quality standards, aligning with its status as a combined ATMP under EMA oversight.

For deployment, our project will be injected under sterile conditions using single-use vials, with strict protocols for the disposal of genetically modified cell waste. In Germany, the use of engineered cells falls under the Gene Technology Act (“Gentechnikgesetz”), requiring approval from the Central Committee on Biological Safety (ZKBS) based on an environmental risk assessment. However, due to the use of non-competitive, encapsulated cells with limited survivability outside the host, we anticipate the environmental risk to be minimal.

Tattoo Studios

Tattoo Regulations in Germany

In Germany, tattoo studios are regulated at the local level by public health authorities, which enforce hygiene standards under ordinances such as the Bavarian Hygiene Ordinance (BayHygV) and the national Tattoo Inks Ordinance (TätowiermittelV). These rules mandate strict sterilization, waste disposal, and documentation practices.

However, tattooing is not classified as a trade under the German Trade and Craft Code (Handwerksordnung), meaning no formal vocational qualifications are legally required to become a tattoo artist. Training often occurs through informal apprenticeships or self-teaching rather than standardized education.

Given this regulatory gap, integrating InkSight into practice would require a hybrid model: tattoo artists would need specialized certification in applying advanced biosensor technology, ensuring they are trained in both technical and biological safety aspects. This approach not only ensures safe implementation but could also help advance official recognition and professionalization within the field.

Application Setting

InkSight’s application sits at the intersection of healthcare and body art, presenting two potential implementation settings — each with distinct advantages and limitations: clinical settings (hospitals / clinics) and tattoo studios.

The former offer a controlled, sterile environment with medically trained staff, ideal for handling living cell products and managing potential adverse reactions—particularly during trials and early adoption. However, medical professionals lack experience in tattooing techniques, which are essential for precise dermal placement of InkSight, and may face capacity constraints for non-essential procedures.

On the other hand, tattoo artists possess unmatched skill in depositing materials accurately and aesthetically in the skin, work in spaces already compliant with strict hygiene laws, and operate in accessible, community-oriented environments. Yet, under current German law, tattooing is not classified as a medical practice, prohibiting artists from administering living cell-based products without medical oversight. In the future, pending demonstrated safety and standardization, a decentralized, studio-based model could become feasible.

Hybrid Model

A hybrid approach may eventually emerge, combining medical oversight with the technical artistry of certified tattoo professionals, though initial deployment will require clinical supervision to meet regulatory and biosafety standards.

Looking ahead, InkSight could be delivered through tattoo studios using pre-packaged, single-use sterile cartridges containing the cell-laden hydrogel, minimizing handling risks. This would require creating a new certified role, the “biomedical tattoo technician”, trained in sterile implantation, basic biology, and safety protocols. Oversight would be shared: local health offices (Gesundheitsämter) would enforce studio hygiene, while state medical boards (Landesärztekammer) would set training standards. This hybrid model aims to decentralize access safely, positioning Germany as a leader in responsibly integrating advanced biotechnologies into community settings.

Collaboration

A key innovation of InkSight lies in its fusion of biotechnology with body art, transforming medical diagnostics into a medium for personal and cultural expression. To meaningfully embed this vision, close collaboration with tattoo artists is essential from the earliest stages of development. Their expertise (including knowledge of skin behavior, pigment dynamics, aesthetic placement, and client experience) directly informs critical design choices, from the visual layout of the tattoo to the adaptation of injection tools for delivering encapsulated cells.

We were already engaging in this co-creative process through interviews, artistic partnerships, and participation in tattoo culture events. Moving forward, we planned to organize practical workshops where artists can trial the procedure using non-biological substitutes in realistic studio settings. This hands-on, iterative collaboration allowed us to identify and solve technical and ergonomic challenges collectively, ensuring the technology is not only safe and functional, but also artistically resonant and practically viable.

Ethical and Societal Implications

Public Perception and Survey Motivation

During early discussions with experts and physicians, it became clear that public acceptance would be a decisive factor in the adoption of technologies based on genetic engineering. Concerns about safety, control, and ethical boundaries emerged repeatedly, reflecting a broader societal reluctance rooted in fear and limited understanding of biotechnology.
To better grasp these perceptions, we conducted a survey aiming to assess the openness of the public toward such technologies and to identify specific fears that may contribute to hesitation or rejection. In designing the questionnaire, we deliberately included questions addressing common fears—even those without scientific basis—to capture the full emotional and perceptual landscape influencing acceptance.

The survey format itself is notable, as it mirrors conditions often encountered in healthcare: practitioners have very limited time to explain complex therapeutic principles, while patients must make decisions with minimal background information. Likewise, in our survey setting, participants received only a brief introduction to the technology, leaving little room for detailed explanation. Yet, unlike in everyday life, survey participants represented a preselected group—individuals already willing and interested enough to engage. In real-world contexts, we must assume a much lower readiness to participate in such discussions.

Our findings confirmed that genetic engineering involving living cells embedded within the skin, and especially concerns about containment and control, constitute one of the dominant fears among respondents.

Consent, Autonomy and Data Security

InkSight is a semi-permanent tattoo that makes health information visible, making informed and voluntary user consent the cornerstone of its ethical application. A certified professional must clearly explain what health information the tattoo reflects, how long it remains active, and how its appearance may change. Users must have full autonomy over the placement and visibility of the tattoo, ensuring personal comfort and privacy.

However, the continuous visibility of biometric data introduces significant ethical risks, including potential coercion, non-consensual monitoring, and discrimination. Employers, insurers, or other third parties must never mandate the use of InkSight or access its data, as this could lead to exclusion, stigmatization, or unfair treatment, especially for vulnerable groups. Although health data is protected under laws like the GDPR, the tattoo’s physical nature could make sensitive information publicly visible, exposing users to social judgment or harassment.

To address this, the core privacy principle of InkSight is that no personal health data is ever digitally stored or transmitted. The sensor operates as a localized, biological interface. The output is solely a visible change in the tattoo’s contrast, which is a biochemical signal without an inherent digital value. The interpretation of this signal is a private matter for the user; only they (and potentially a trusted medical professional they choose to show) can assign meaning to it. This design ensures that the most sensitive information never enters a data stream, fundamentally bypassing the risks associated with data breaches, cloud storage, or unauthorized access. By keeping the data analog and user-interpreted, we place ultimate control and ownership directly with the individual.

Psychological Impacts

We firmly oppose any mandatory or non-consensual use of this technology. To safeguard individual rights, we urge the development of strengthened legal frameworks that explicitly prohibit coercive applications and extend privacy protections to cover visible biometric data. Additionally, all consent procedures must be administered by trained professionals to ensure participation is always voluntary, fully understood, and entirely controlled by the user.

InkSight offers a dual psychological experience: it can empower users by providing real-time health reassurance and encouraging proactive behaviors, yet it may also provoke anxiety, obsessive self-monitoring, or emotional distress — particularly for those managing chronic or stigmatized conditions.

To mitigate these risks, we emphasize the critical importance of selecting biomarkers with high clinical specificity and relevance, reducing the likelihood of false positives that could lead to unnecessary worry or medical interventions. Each potential biomarker must be carefully evaluated to balance its benefits against the psychological risks of constant visibility and potential misinterpretation.

Ultimately, transparent user education is essential. Certified professionals must clearly communicate the technology’s limitations and potential psychological impacts during the consent process, ensuring users make fully informed decisions aligned with their personal health needs and emotional well-being.

Accesibilty and Equity

InkSight was conceived to enhance diagnostic accessibility by offering continuous, equipment-free health monitoring directly on the skin, potentially reducing dependence on clinical visits and lowering healthcare barriers — especially for underserved communities.

However, as a advanced biomedical product, it risks exacerbating health inequities if high costs or limited insurance coverage restrict access to privileged groups. To prevent this, we advocate for public health systems to evaluate InkSight’s medical benefit and cost-effectiveness for possible reimbursement, rather than allowing it to become a luxury commodity. We also support exploring open-source models and global partnerships to extend reach beyond high-income regions.

In addition, inclusivity must be central to InkSight’s development. Clinical testing must include participants across the full spectrum of skin pigmentation, as melanin-based readouts may show reduced contrast on darker skin—a concern that mirrors broader issues of racial bias in medical technology. To overcome this limitation, we are investigating alternative, high-contrast pigments to ensure reliable visibility and diagnostic utility for all users, regardless of skin tone.

Policy Analysis

Our Policy Analysis stands as both the culmination of our interdisciplinary efforts and a guiding pillar of our safety approach. It brings together expert insights, survey data, and stakeholder feedback to examine how governance, legislation, and socio-technical considerations shape the current and future development of InkSight. Learn more about the discussions that shaped our Safety approach, including an exploration of the diverse feedback behind it on our Human Practices page.

The full document below explores these topics in greater depth, detailing our reflections and opening up conversations about hybrid models bridging art and medicine, future implications of health-monitoring biotechnologies, and the societal impacts such innovations may bring. We hope it serves as a useful reference for those navigating the intersections of safety, security, ethics, and responsible innovation in SynBio.

General Lab Safety

All research conducted by the iGEM Munich 2025 team was in accordance with the iGEM safety policies and regulations. All organisms used and all parts generated by this team are on the whitelist or were approved by iGEM via a Check-In. The team conducted its work in the laboratories of Prof. Dr. Gil Westmeyer at the Munich Institute of Biomedical Engineering of the Technical University of Munich.

Safety Training

Theoretical Safety Training

In order to reinforce the management of the labs, prior to initiating any laboratory work all team members successfully completed a mandatory and comprehensive safety training program by the official institutional biosafety officer (Josef Hintermair) of our facility. This training was designed to ensure a thorough understanding of potential hazards and the implementation of rigorous safety protocols, based on BGI 850-0 (Deutsche Gesetzliche Unfallversicherung (DGUV), 2020), §14 of The Hazardous Substances Ordinance (GefStoffV)(Bundesrepublik Deutschland, 2010) and safety policies of the TUM School of Natural Sciences, thereby promoting a culture of responsibility and risk mitigation of our project.

During this training, we encompassed several key domains fundamental to laboratory safety: Personal Protective Equipment (PPE), emergency response protocols, inventory controls, out of hours policy, chemical and biological hazard management.

This was followed by a comprehensive review of Emergency Response Procedures, which outlined clear steps for potential incidents such as chemical spills and biological exposures. Finally, the training covered standard microbiological practices, including aseptic technique and waste disposal, and reviewed the specific biosafety levels applicable to our work with non-pathogenic organisms. We updated our safety procedures whenever we introduced new substances or organisms to the lab during our project.

Practical Safety Training

Following the theoretical components, the team participated in a guided orientation tour of all laboratory spaces we were authorized to use. This practical walk-through was essential for contextualizing safety knowledge within our specific working environment. During this orientation, the locations of all critical safety infrastructure were explicitly identified and demonstrated:

• All primary and secondary emergency exits were confirmed to be clearly marked and unobstructed; and strategically located emergency collection points were discussed.
• The operation of all emergency equipment, including safety showers, eyewash stations, fire alarm pull and fire extinguisher was explained.
• The locations of fully stocked first-aid kits were indicated.
• Specific hazards within the lab were pointed out, including storage areas of flammable solvents and cryogenic material.
• Designated waste streams for biological, chemical and sharp disposal were reviewed.
• Familiarization with a master list of all emergency contact personnel and authorities were posted prominently at the laboratory’s main entrance.
• Emergency Infrastructure: Clear designation and familiarization with emergency stop-buttons for machinery.

To formalize the training and ensure complete comprehension, all team members were required to pass two written examinations assessing their knowledge of the presented safety material and emergency procedures. On top of that, every team member provided a proof of insurance in order to work in the lab.

In Case of Emergency

In a laboratory environment, preparedness is the cornerstone of safety. Emergencies can happen unexpectedly, and a calm, informed response is critical to minimizing harm to personnel, equipment, and the environment. In case of fire, gas or smoke detection, we were adviced to follow the R.A.C.E. protocol:

• Rescue: Anyone in immediate danger. Assist in evacuating the area if you can do so safely.
• Alarm: Activate the nearest alarm pull station.
• Contain: If it is safe to do so, close all doors and windows behind you as you leave.
• Evacuate: Leave the building immediately using the nearest stairwell. Do not use elevators.

After evacuation, it is crucial to proceed directly to the designated emergency assembly point and not re-enter the building.

Lab Safety

Guidelines and Risk Assessment

Within the laboratory, the use of appropriate PPE (including lab coats, safety goggles, and disposable gloves) was strictly enforced at all times. A key point was that closed-toe, closed-heel shoes must be worn at all times to protect against spills and dropped objects. Furthermore, a strict no eating or drinking policy was enforced in the lab to prevent accidental ingestion of hazardous materials. To maintain a controlled and secure environment and to minimize potential hazards, laboratory access was restricted exclusively to trained team members and supervising personnel; external visitors were not permitted without prior authorization and escort.

Our lab employed a systematic five-step risk assessment process (World Health Organization, 2020) to proactively manage potential hazards:

1. Gathering information: We identified all materials, equipment, and procedures involved in an experiment and consult relevant Safety Data Sheets.
2. Evaluating the risks: We determined the likelihood and potential severity of incidents like exposure, spills, or injury.
3. Developing a risk control strategy: We prioritized the elimination of hazards where possible, followed by implementing engineering controls and administrative changes.
4. Selecting measures: We implemented the specific control measures, such as using a fume hood, establishing decontamination protocols, or mandating specific gloves.
5. Reviewing assessments regularly: We assessed our procedures to ensure our safety measures remain effective and relevant. This cyclical process ensured a continuous commitment to a safe working environment.

Experimental Safety

While our general safety guidelines provide the essential foundation for a secure lab environment, we proactively implemented additional, specific measures to address the unique risks of our research. A prime example of this commitment was our use of SYBR^TM Safe DNA Gel Stain (ThermoFisher) for all gel electrophoresis procedures, thereby eliminating the risks associated with ethidium bromide (EtBr). SYBR Safe is an alternative designed to be non-mutagenic, binding preferentially to DNA without permanently intercalating, offering a decreased health risk to lab personnel and simplifying a sustainable waste disposal.

Building on this principle of hazard control, our containment and sterilization protocols were designed to protect both the integrity of our experiments and the wider environment. When handling mammalian cell cultures and other sensitive materials, we utilized a biosafety cabinet for all procedures to ensure a sterile environment and to contain any potential aerosols. All equipment and surfaces were systematically decontaminated, and materials were sterilized under UV light where appropriate. We implemented tailored decontamination measures (including Ethanol, Bacillol, Mucocit, and UV light) to address specific risks and ensure effective containment across all laboratory procedures.

Although our laboratory work involved the use of hazardous materials, including heavy metals, carcinogens, and corrosive chemicals, all procedures were conducted under strict control measures. Furthermore, all novel genetic parts designed for our project were rigorously assessed and found to be non-hazardous both individually and within the final system. All DNA was sourced exclusively from members of the International Gene Synthesis Consortium (IGSC), guaranteeing compliance with global screening protocols against pathogenicity and dual-use concerns.

All of our experiments were conducted using exclusively non-pathogenic, Biosafety Level 1 (BSL-1) bacterial strains, specifically E. coli BL21 and DH5α, which are well-characterized and pose minimal risk (Chart et al., 2000) to healthy humans and the environment.

Maintaining experimental safety in our mammalian cell culture lab was achieved through a series of standardized procedures proposed by Bundesagentur für Arbeitsschutz und Arbeitsmedizin (BAuA). All our work was traceable to validated master cell banks, with working cell stocks used for daily experiments. To ensure purity and authenticity, we routinely tested our HEK 293T cell cultures for contamination and verified cell line identity through checks for morphology and growth patterns. All work was conducted using sterile media and solutions within a biological safety cabinet that underwent regular sterilization. Furthermore, all media and solutions were sterile for use, and a strict protocol of clear, unambiguous labelling was enforced on all vessels and containers.

One of the main objectives of InkSight was the robust expression of tyrosinases, the key enzymes for melanin production. In a dedicated effort to prioritize safety-by-design, we proactively utilized a cell-free expression system to test over 20 different tyrosinase variants. This strategy was pursued to create a inherently safer alternative (Garenne et al., 2021) to live, engineered cells, as a cell-free system is functionally inert and eliminates risks of proliferation or gene transfer. We successfully designed and executed these expression experiments; however, analysis via BCA assay and Western Blot confirmed a lack of detectable protein yield across all tested variants. While this path was not technically viable for our platform, this extensive investigation powerfully demonstrates our commitment to exhausting safer alternatives as a primary step in our development process.

Learn more about our Tyrosinase Engineering cycle!

We also integrated advanced computational tools into our design process, utilizing artificial intelligence for genetic circuit prediction and protein structure modeling. These tools operated purely in silico and were employed to enhance the precision and safety of our designs, presenting no physical risk in the laboratory environment.

Finally, we carefully moderated the application of antibiotics, acknowledging their multifaced roles (Sengupta et al., 2013) in selection while mitigating their threat as promoters of antimicrobial resistance, to prevent any environmental release. We utilized Carbenicillin for bacterial selection and Pen-Strep for mammalian selection.

Waste Disposal and Sterlization by Autoclaving

All laboratory processes, while designed to yield valuable scientific outputs, concomitantly generate waste streams that require management. Our team adheres to a strict waste segregation protocol in accordance with institutional (TUM) and German safety regulations (BG RCI / DGUV, 2020) to ensure environmental protection and personnel safety.

Waste was categorically separated into two primary streams: non-hazardous (industrial) and hazardous laboratory waste. The former category encompassed materials not contaminated by biological or chemical agents and can be further segregated into packaging materials, cardboard and paper as well as non-contaminated equipment. Each stream was collected in dedicated, clearly labeled and suitable containers to facilitate recycling and responsible disposal.

The second category included all materials with inherent chemical, biological, or physical hazards, which our team rigorously separated. All biohazardous materials, including culture media, recombinant bacterial cells and agar plates were inactivated by autoclaving prior to disposal as solid chemical waste. All liquid chemical waste was segregated into dedicated, chemically compatible containers that were clearly labeled by hazard category.

Electric Devices

The operation of electrical equipment in a wet-lab environment presents a significant risk of electrical hazards. To mitigate this risk, our team and institution implements scheduled regulatory testing and inspections of all laboratory instruments as mandated by German safety standards (such as DIN EN 61010-1 (Europäische Norm / VDE Verlag, 2020)). This ensures their ongoing electrical safety and functional integrity.

On top of that, no team member was permitted to operate any device without first undergoing specific, hands-on training from a qualified lab supervisor or group member. This training covered correct operation, safety precautions, and emergency shutdown.

This integrated approach ensures a safe working environment, minimizing risk to personnel and ensuring the integrity of our experimental procedures.

References