30‐Channel Microcoil System for High‐Throughput Metabolic Flux Analysis Using Hyperpolarized <sup>13</sup> C NMR Spectroscopy

Hyperpolarized (HP) carbon-13 labeled compounds have significantly advanced metabolic research, enabling real-time, non-invasive tracking of metabolic processes in vivo and ex vivo. These techniques are particularly valuable for studying diseases characterized by altered metabolism, such as cancer, but their high cost and technical complexity limit broader adoption. A critical need exists for cost-effective, high-throughput methods to maximize the utility of these tracers in translational research. In this study, we present a 30-channel microcoil receiver array that enables simultaneous metabolic flux measurements across 30 samples using a single HP dissolution. This system represents a significant increase in throughput compared to previous setups. Using a single dissolution of HP [1-<sup>13</sup>C]pyruvate, we demonstrate the system's ability to detect significant changes in pyruvate-to-lactate conversion in acute myeloblastic leukemia ML-1 cells treated with 2-deoxy-d-glucose. This was achieved with high statistical power ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics><mml:mrow><mml:mi>p</mml:mi> <mml:mo><</mml:mo> <mml:mn>0.001</mml:mn></mml:mrow> <mml:annotation>$$ p<0.001 $$</mml:annotation></mml:semantics> </mml:math> ), despite inter-plate variability in perfusion rates of HP pyruvate. This work establishes a new benchmark for high-throughput HP technologies, achieving high statistical power per pyruvate dissolution. By addressing key limitations and optimizing current designs, this technology holds potential in translational metabolic research, particularly in resource-intensive applications such as drug screening and disease modeling. Furthermore, the modular design of the microcoil array is adaptable for a variety of sample types, including tissues, organoids, and patient-derived models. This versatility positions the system as a promising tool for translational research in metabolic diseases, extending beyond oncology to conditions such as diabetes, neurodegeneration, and cardiovascular disorders.

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Journal
NMR in Biomedicine
Published
2025-11-10
DOI
https://doi.org/10.1002/nbm.70174
Primary Topic
Advanced NMR Techniques and Applications
Type
article
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article

30‐Channel Microcoil System for High‐Throughput Metabolic Flux Analysis Using Hyperpolarized 13 C NMR Spectroscopy

Juan Diego Sánchez, Esben Søvsø Szocska Hansen, Nichlas Vous Christensen, Christoffer Laustsen et al.
NMR in Biomedicine
Advanced NMR Techniques and Applications
article

30‐Channel Microcoil System for High‐Throughput Metabolic Flux Analysis Using Hyperpolarized 13 C NMR Spectroscopy

Juan Diego Sánchez, Esben Søvsø Szocska Hansen, Nichlas Vous Christensen, Christoffer Laustsen, Lotte Bonde Bertelsen, Sissel Ellemose Liboriussen
article en

Abstract

Hyperpolarized (HP) carbon-13 labeled compounds have significantly advanced metabolic research, enabling real-time, non-invasive tracking of metabolic processes in vivo and ex vivo. These techniques are particularly valuable for studying diseases characterized by altered metabolism, such as cancer, but their high cost and technical complexity limit broader adoption. A critical need exists for cost-effective, high-throughput methods to maximize the utility of these tracers in translational research. In this study, we present a 30-channel microcoil receiver array that enables simultaneous metabolic flux measurements across 30 samples using a single HP dissolution. This system represents a significant increase in throughput compared to previous setups. Using a single dissolution of HP [1-<sup>13</sup>C]pyruvate, we demonstrate the system's ability to detect significant changes in pyruvate-to-lactate conversion in acute myeloblastic leukemia ML-1 cells treated with 2-deoxy-d-glucose. This was achieved with high statistical power ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics><mml:mrow><mml:mi>p</mml:mi> <mml:mo><</mml:mo> <mml:mn>0.001</mml:mn></mml:mrow> <mml:annotation>$$ p<0.001 $$</mml:annotation></mml:semantics> </mml:math> ), despite inter-plate variability in perfusion rates of HP pyruvate. This work establishes a new benchmark for high-throughput HP technologies, achieving high statistical power per pyruvate dissolution. By addressing key limitations and optimizing current designs, this technology holds potential in translational metabolic research, particularly in resource-intensive applications such as drug screening and disease modeling. Furthermore, the modular design of the microcoil array is adaptable for a variety of sample types, including tissues, organoids, and patient-derived models. This versatility positions the system as a promising tool for translational research in metabolic diseases, extending beyond oncology to conditions such as diabetes, neurodegeneration, and cardiovascular disorders.

NMR in BiomedicineVol. 38(12)
Aarhus University (DK), Universidad Politécnica de Cartagena (ES), Hamburg Institut (Germany) (DE)
Openalex Percentile: Top 69%
Advanced NMR Techniques and Applications
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