nPRISM

Netherlands Platform for Research & Innovation in Single-Molecule Biology

nPRISM is a national research facility that focuses on studying the building blocks of life such as DNA and proteins. Utilizing cutting-edge nanotechnology, and advanced fluorescence, force, label-free spectroscopy and combinations thereof, the center allows researchers to image, probe, and manipulate single molecules including DNA, RNA, proteins, and protein complexes to understand how they fold, move and interact. Insights gained from these fundamental studies on biological processes will lead to revolutions in novel therapeutic strategies and technological solutions to major societal challenges.

Website nPRISM

Infrastructure and User Services  

nPRISM houses state-of-the-art instrumentation to enable imaging, manipulation, and high-throughput analysis of individual biomolecules with exceptional precision and temporal resolution. Single-molecule fluorescence microscopes including super-resolution imaging systems will provide nanometer-scale localization and real-time tracking of biomolecules in vitro and in live cells. The center offers AFM and high-speed AFM (HS-AFM), the latter enabling real-time visualization of biomolecular dynamics at the nanometer scale up to video rates (20 frames per second). For single-molecule manipulation, the facility features optical tweezers, acoustic force spectroscopy and high-throughput magnetic tweezers. These assays also exist combined with fluorescence to enable  correlative force, torque and fluorescence spectroscopy, allowing the users to apply and measure piconewton forces while monitoring the composition of biomolecular complexes with fluorescence to study molecular mechanics, (un)folding pathways, and biomolecular interactions. 

Furthermore, we also provide label-free microscopy, e.g. iSCAT, to monitor complex molecular size. Additionally, massively parallel single-molecule imaging platforms for high-throughput sequencing and molecular interaction studies (SPARXS) are available. Complementary technologies such as fluorescence correlation spectroscopy (FCS) and single-molecule fluorescence resonance energy transfer further expand the center’s capabilities. Additionally, the center supports nanopore-based technologies, offering label-free, electrical detection and sequencing of biomolecules such as DNA, RNA, and proteins, allowing users to characterize molecular features with high throughput and single-molecule sensitivity. Lastly, the center will also support users with advanced data analysis of their experiments. 

Examples/description of the type of research  

nPRISM is dedicated to unraveling the fundamental principles governing biomolecular function by directly imaging, probing, and manipulating individual biological molecules. Traditional ensemble-based biochemical and biophysical methods provide averaged measurements across large populations, often masking rare, transient, or heterogeneous molecular states that are essential for understanding biological processes at the molecular level. Single-molecule techniques overcome these limitations by allowing the observation of molecular conformations, dynamics, and interactions at the level of individual molecules. By leveraging advanced fluorescence microscopy, force spectroscopy, time-resolved electron microscopy and the opportunities of nanotechnology, the center will enable direct visualization of biomolecular interactions, conformational changes and the forces involved in real time.  

Additionally, the ability to track individual biomolecules in live cells will provide a window into the spatial and temporal organization of biological pathways. The insights gained from single-molecule studies have broad implications for synthetic biology, molecular medicine, and drug discovery, as they allow precise characterization of biomolecular function at a level that informs therapeutic development. nPRISM will serve as a national hub for interdisciplinary collaboration, bringing together biophysicists, chemists, structural biologists, and biomedical researchers. By fostering innovation in single-molecule applications, it aims to push the frontiers of molecular biology to offer transformative insights into the fundamental processes that sustain life. 

How to access the infrastructure ?

nPRISM will operate an open-access model, ensuring broad availability to academic, industrial, and public-sector researchers. Access will be granted primarily based on scientific excellence through a transparent proposal evaluation process. Approximately 70% of capacity will be allocated to academic users (internal and external), 20% reserved for industrial collaborations and contract research, and 10% for public purposes (research supporting public health and related training programs and workshops). A fee structure will apply to industrial users, while academic access will be subsidized. Usage statistics and access procedures will be monitored to ensure fair distribution and optimal utilization. 

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