Programmable photolithographic peptide synthesis
PhD - Leuven | Just now
Peptides are short chains of amino acids that play essential roles in biology, from cell signalling and immune recognition to drug discovery and protein engineering. Today, however, making many different peptides in a precise and scalable way remains technically demanding. This PhD project explores a new approach to peptide synthesis inspired by semiconductor manufacturing, where light is used to define patterns with very high precision. The central question is whether similar light-directed principles can be used to build peptides at selected locations on a surface, enabling the programmable construction of peptide structures and high-density peptide arrays.
To achieve this, the student will investigate how peptide building blocks can be added step by step on functionalized surfaces, while using light to control where each reaction takes place. The work will address fundamental scientific questions in photochemistry, peptide chemistry, and surface science, including light-triggered deprotection mechanisms, reaction kinetics, synthesis fidelity, spatial confinement of reactive species, and molecular pattern formation. A key challenge will be to make reactions happen efficiently at illuminated sites while preventing unintended reactions in neighbouring areas.
The project combines hands-on chemistry with optics, microfluidics, analytical characterization, and software-controlled synthesis workflows. By bringing these disciplines together, the research aims to establish the foundations of a new platform for light-directed peptide synthesis. If successful, this technology could make it possible to create large libraries of peptides directly on chip-based substrates, opening new routes for biomolecular discovery, protein engineering, and future programmable manufacturing of biologically relevant molecules. The project offers a unique opportunity to contribute to an emerging field at the interface of semiconductor technology and biotechnology within imec’s programmable biology activities.
What you will do
- Develop and optimize peptide synthesis chemistry on functionalized surfaces, with emphasis on making solid-phase peptide chemistry compatible with spatially controlled, light-directed workflows.
- Investigate photo-activated deprotection strategies and reaction conditions that enable efficient peptide chain growth while minimizing side reactions and incomplete coupling.
- Quantify spatial confinement and cross-talk between neighbouring synthesis sites using well-designed model reactions, patterned exposures, and suitable chemical readouts.
- Characterize synthesis quality, yield, fidelity, and release of surface-grown peptides using state-of-the-art analytical techniques and representative model sequences.
- Integrate chemistry, optics, fluidics, and software-controlled synthesis protocols into a prototype workflow for programmable peptide synthesis.
Who you are
- You hold an MSc in chemistry, biochemistry, biotechnology, bioengineering, chemical engineering, biomedical engineering, or a closely related discipline.
- You are motivated to work at the interface of peptide chemistry, photochemistry, surface science, and bioengineering.
- You enjoy hands-on experimental research and are willing to iteratively optimize challenging chemical processes on surfaces.
- You have a strong interest in analytical characterization and in understanding how reaction conditions affect synthesis quality, fidelity, and spatial confinement.
- You communicate clearly, work carefully and reproducibly, and are eager to collaborate across chemistry, optics, microfluidics, and semiconductor technology.
Required background: Chemistry, Biochemistry, Bioengineering, Chemical engineering, or a closely related discipline.
Type of work: 70% experimental, 20% modelling, 10% literature
Supervisor: Liesbet Lagae (KU Leuven)
Daily advisor: Kherim Willems, Kathrin Hoelz
The reference code for this position is 2027-120. Mention this reference code in your application.