Measuring Cancer Metabolism at the Single-Cell Level
Toward metabolic MRI of an individual cancer cell
A cell is defined not only by the molecular markers it carries, but also by the biological processes it performs.
Metabolic reprogramming is a characteristic feature of cancer. One of its best-known manifestations is increased glycolytic activity and the conversion of pyruvate into lactate, even under conditions in which oxygen is available. Hyperpolarized carbon-13 magnetic resonance can make this conversion observable in real time and has already been used to investigate metabolic activity in tissues, tumors and larger cell populations.
Resolving the same process at the level of an individual cell remains a substantially greater challenge. Conventional magnetic resonance methods typically require much larger sample volumes and therefore report an average across many cells. Such ensemble measurements can conceal biologically relevant differences between individual cells.
Single-cell metabolic measurements could reveal a different dimension of cellular heterogeneity: not only which molecules a cell expresses, but how actively it performs a particular biological process. Diamond nitrogen-vacancy quantum sensors provide a potential route toward magnetic resonance measurements in the exceptionally small sample volumes required for this type of analysis.
Measuring cellular function rather than surface-marker expression
Qtas will work with Prof. Dominik Bucher at the Technical University of Munich and Prof. Franz Schilling at TUM University Hospital on a proof-of-concept project exploring metabolic magnetic resonance at the single-cell level.
The project will combine hyperpolarized carbon-13 magnetic resonance with diamond quantum sensing. Hyperpolarized [1−13C]pyruvate is introduced as a metabolic substrate. If it is transported into the cell and participates in the relevant metabolic pathways, a portion of its carbon-13 signal can subsequently appear in lactate.
The central question is whether this pyruvate-to-lactate conversion can be detected from a measurement volume containing just one cancer cell.
The experiment will be conducted in a controlled cell-line model and includes cell-free and biological controls. In addition to evaluating signal detectability and reproducibility, the project examines whether the measurement materially affects the cell.
Hyperpolarized 13C magnetic resonance is an established approach for observing dynamic metabolic processes, while Prof. Schilling’s research focuses on hyperpolarized compounds and metabolic magnetic resonance imaging. Prof. Bucher’s group develops NV-centre-based quantum sensors for NMR spectroscopy at micro- and single-cell-relevant length scales.
Toward surface-marker-independent qMRI
Qtas currently detects rare cells through specific magnetic labels directed at selected cellular markers. This enables highly sensitive detection and recovery but, as with other affinity-based approaches, the biological question is defined partly by the markers selected in advance.
The metabolic project explores a complementary principle. Rather than identifying a cell primarily through a surface-bound antibody, it investigates whether the cell can be characterized through a functional process taking place within it.
Because the present experiment uses isotopically labelled, hyperpolarized pyruvate, it is not strictly label-free. It is, however, independent of cell-surface marker expression. This distinction is important: cells with different surface phenotypes could potentially be assessed through a shared or divergent metabolic function.
In the longer term, combining functional magnetic resonance with Qtas’ ability to detect and recover intact individual cells could support a platform that connects three layers of biological information:
cellular identity, functional state and downstream molecular composition.
Why single-cell metabolism matters
Two cells belonging to the same tumor can carry similar classification markers while behaving differently. Differences in metabolic state may reflect variation in proliferation, environmental stress, treatment response or cellular adaptation.
Population-level measurements average these differences. A single-cell metabolic readout could instead allow researchers to investigate how functional activity varies from cell to cell and whether distinct metabolic states correspond to meaningful molecular subpopulations.
The current project is an early technical proof of concept. It does not evaluate patient samples, diagnose cancer or establish clinical validity. Its purpose is to determine whether a defined metabolic conversion can be detected at the single-cell scale while preserving the measured cell.
Success would provide an experimental foundation for future work on functional cell phenotyping, metabolic heterogeneity and surface-marker-independent analysis of rare cells.
Collaboration
The project will be conducted by Qtas, the Technical University of Munich and TUM University Hospital, with Prof. Dominik Bucher and Prof. Franz Schilling, and is supported by the Munich Center for Quantum Science and Technology, MCQST.
Exploring the future of functional single-cell analysis
Qtas welcomes scientific collaborations at the intersection of quantum sensing, cancer metabolism, hyperpolarized magnetic resonance and next-generation single-cell analysis.
