PAC-ROPHAGE: Teaching Macrophage Phagocytosis through Game Play

Introduction: : Science literacy is essential for informed decision-making and critical thinking, especially in today’s world of rapid scientific advancement. The COVID-19 pandemic has emphasized the need for public understanding of scientific concepts, particularly in fields such as immunology and biomedical engineering. For biomedical topics that span multiple disciplines, such as immune system behavior, educational games can help visualize abstract and invisible processes in an accessible and engaging way. Traditional teaching methods, which focus heavily on memorization, often fail to convey how individual cells function independently and within coordinated biological systems. These persistent challenges underscore the need for new teaching strategies focusing on dynamic cell functionality rather than static structure.
One promising solution is game-based learning, which has proven effective in promoting student engagement, motivation, and deeper understanding. Unlike passive instruction, educational games immerse learners in interactive environments that encourage systems thinking and contextual application. For complex subjects like immunology, games offer a way to visualize dynamic cellular interactions. Inspired by the classic Pac-Man game, we developed Pac-rophage, an educational tool that simulates macrophage behavior during immune responses. By leveraging familiar mechanics, the game integrates learning into gameplay, allowing students to build a framework for understanding concepts such as phagocytosis and viral destruction. Supplementary materials, including instructional videos and guides, further support comprehension.
Here, we detail the conceptualization, design, and testing of Pac-rophage as a prototype tool in biomedical science education. Our goal is to demonstrate how thoughtful game design can enhance science education, particularly among younger learners and undergraduate students.

Materials and

Methods: : Component Preparation: We developed and fabricated Pac-rophage, based on the retro-themed well-known Pac-Man board (Figure 1A-D). We designed the Pac-rophage and pathogen characters—representing viruses and apoptotic cells—in SolidWorks, and then 3D-printed each of the game pieces. The other game components (board, tokens, and cards) were designed in Adobe Illustrator, printed, and assembled. An instructional video and guide introduced immune system principles, including phagocytosis, pathogen recognition, and antigen presentation, using cartoon visuals and character-based storytelling.
Gameplay: Players take turns navigating the board, collecting antigen tokens, activating immune responses, and simulating pathogen clearance. Antigen collection enables Pac-rophage to become an Antigen-Presenting Cell (APC), gaining the ability to eliminate matching pathogens. Vaccine tokens, drawn via action cards, temporarily introduce a second Pac-rophage, reinforcing the role of vaccination in boosting immune response.
Testing: Gameplay was first piloted in a 50-minute class session with 70 undergraduate students in Fall 2024. Introduction to Bioengineering (BIOE 120) is a seminar-style course for non-majors from diverse academic backgrounds at the University of Illinois (Fig E-H). Each group recorded gameplay statistics, and students completed pre- and post-surveys assessing understanding of immune concepts. In Spring 2025, gameplay was repeated in Immunoengineering (BIOE 434), an upper-level elective for undergraduates or graduate students with a biological background, to gain further insight into the game mechanics and future improvements. Quantitative Likert-scale survey data were analyzed using ANOVA and t-tests, while qualitative responses were thematically grouped using AI-assisted coding followed by manual review.

Results, Conclusions, and Discussions:: We evaluated the finalized Pac-rophage prototype, where the survey results revealed increased familiarity with both the game mechanics and immunology content for students in BIOE 120. Following the instructional video, 27.9% more students reported understanding how to play the game, and 80% shifted from agreeing to strongly agreeing that the game’s concept was clear. Increases in students’ understanding were observed across key concepts of immunology and immunoengineering, including vaccines, pathogens, infection, immune cells and their functions, antigens and antibodies (in order of ranking). These results suggest that both the video and gameplay effectively reinforced content.
Gameplay data supported a steep learning curve. The average time to complete a first round was 21.73 ± 12.62 minutes, dropping to 8.88 ± 6.17 minutes by the third round, indicating rapid adaptation to game mechanics. Strategic gameplay also influenced learning outcomes; players who acquired vaccine tokens or antigen helmets had up to a 400% greater chance of winning, effectively modeling how preparedness enhances immune protection. In contrast, Pac-rophage characters lacking key resources were significantly more likely to lose, reinforcing real-world immunological dynamics. Finally, thematically coded qualitative survey responses indicated that students strongly enjoy the game design and aesthetics (36.8%), educational and learning value (21%), and engagement (18.4% of responses)
These findings demonstrate the educational potential of Pac-rophage, a game that combines narrative-driven strategy with scientifically accurate content. The game provides an experiential platform to explore immune responses, promoting deeper engagement and comprehension. However, even with clear instructional materials, students required a full round of gameplay to internalize rules and strategies, highlighting the need for active participation and potentially more structured practice in future iterations. These types of games provide a platform to explore and communicate biomedical topics in a more accessible and engaging way. As we continue to assess retention (or recall) and engagement, we aim to further enhance science literacy among younger students.

Acknowledgements and/or References (Optional)::