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. 2025 Dec 18;20(1):5–13. doi: 10.1021/acsnano.4c14828

Quantum Life Science: A Paradigm for Life Science Research

Hidetoshi Kono †,‡,*, Hiroshi Yukawa †,‡,*, Takeshi Hiromoto †, Ryuji Igarashi †,‡, Yoichi Takakusagi †,‡, Motoyasu Adachi †,‡, Yoshinobu Baba †,*
PMCID: PMC12822533  PMID: 41412569

Abstract

Quantum Life Science integrates quantum technology with life sciences, focusing on three key areas: nanoscale quantum biosensors, quantum technology-based hyperpolarized MRI/NMR, and quantum biology. Nanodiamonds with nitrogen-vacancy centers serve as cellular sensors, while hyperpolarized MRI/NMR techniques enhance metabolic imaging sensitivity. Quantum effects in biological systems, such as photosynthesis, magnetoreception, and enzyme catalysis, inspire biomimetic technologies. This field advances drug discovery, medical diagnostics, and understanding complex biological phenomena. Future developments may include accessible hyperpolarization technologies and quantum-inspired nanotechnologies with potential applications in energy harvesting and medical imaging. This interdisciplinary approach bridges quantum physics, biology, and technology, providing opportunities for scientific exploration and practical applications in various fields.

Keywords: quantum life science, nanoscale quantum biosensors, hyperpolarized MRI/NMR, quantum biology, NVC

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1. Introduction

Quantum Life Science is an emerging interdisciplinary field bridging quantum technologies and life sciences. This field focuses on two key areas: developing quantum sensing technologies for life science applications and understanding quantum phenomena that occur in biological systems. Japan has established several pioneering research centers to integrate quantum technology into biology and life sciences, embodying Sydney Brenner’s philosophy that “Progress in science depends on new techniques, new discoveries and new ideas, probably in that order." In 2019, the "Quantum Life Science Field" was established at the National Institutes for Quantum Science and Technology (QST), and it was reorganized into the "Institute for Quantum Life Science" in April 2021 as the first dedicated institution in this field. Around the same time, the University of Osaka established the Center for Quantum Information and Quantum Biology in 2020, with a primary focus on quantum information applications. More recently, University of Tsukuba launched the Center for Quantum and Information Life Sciences in 2022, which also emphasizes quantum information approaches to biological systems.

In the United States, the Quantum Biology Center at UCLA has been established in 2021 to promote interdisciplinary research combining quantum physics, biology, chemistry, and engineering, aiming to deepen our understanding of life at the nanoscale and foster the next generation of quantum biologists. Similarly, the Quantum Biology and Biophysics Ecosystem (QuBBE), funded by the National Science Foundation in 2021 and led by the University of Chicago, focuses on advancing quantum sensing applications in biological environments, and actively integrates education and workforce development to accelerate the convergence of quantum and biological sciences.

In Europe, the United Kingdom and Sweden have established comprehensive training and research programs. The Leverhulme Quantum Biology Doctoral Training Centre (QB-DTC) at the University of Surrey has begun training a new generation of scientists who can operate across the boundaries of biology, chemistry and quantum physics to pioneer research in quantum biology. In 2022, a national consortium, Quantum Life Science (QLS) Centre, including WACQT, AstraZeneca, IBM, Karolinska Institutet, SAS Institute, and Swelife, was established in Sweden. The primary aim of the center is to establish a foundation for national and Nordic collaboration in the QLS field, thereby promoting and accelerating the development and utilization of QLS applications. Germany has taken a translational approach through commercial applications. NVision, a spin-off from Center of Quantum BioScience at Ulm University, provides a quantum-based platform that polarizes natural metabolites, enabling these safe molecules to be used as an agent for imaging tumor metabolism via standard Magnetic Resonance Imaging (MRI). The center has been established not only to advance collaborative research at the intersection of quantum science and technology with chemistry, biology, and medicine, but also to educate young scientists in the fundamental and applied quantum fields.

The global expansion of quantum life science initiatives reflects the field’s potential to revolutionize our understanding of biological systems and enable novel approaches in biomedical research, diagnostics, and therapeutics. This perspective discusses three primary research directions: nanoscale quantum biosensors for unprecedented biological measurements, quantum-enhanced hyperpolarized MRI/NMR techniques for advanced imaging capabilities, and the emerging domains of quantum biology and quantum biotechnology for understanding and manipulating quantum effects in living systems.

2. Nanoscale Quantum Biosensors

Nanodiamonds with nitrogen-vacancy (NV) centers achieve extremely high sensitivity at the single-molecule level because their electron spin state can be optically manipulated and detected (using Optically Detected Magnetic Resonance, or ODMR). Such property enables us to obtain physical and chemical parameters like temperature, pH, magnetic field, and electric field in cellular environment. Since NVCs are biologically safe, their application for life science is progressing in recent years. − While this paper focuses specifically on nanodiamonds with nitrogen vacancy centers, the mechanisms and bottlenecks are closely related to more general quantum diamond sensors, as thoroughly reviewed by Du et al.

2.1. Nanodiamonds with Nitrogen Vacancy Centers (NVCs)

Diamonds have a crystalline structure made up of covalent bonds of carbon, and they are valued as precious stones because of their excellent light scattering properties. However, as an insulator, it is unsuitable for direct use as a sensing material in its natural state. On the other hand, nanodiamonds with NVCs, which are formed by nitrogen and vacancies, are nanometer-sized diamond particles that contain impurities such as nitrogen and vacancies in the diamond lattice and exhibit fluorescence due to their semiconductor-like energy band gap (Figure ). To apply nanodiamonds with NVCs as nanoscale quantum sensors, after specific spin manipulation and time evolution, the perturbation from the microenvironment to the NVC is measured as a spin distribution. For example, spin manipulation can be achieved using continuous optically detected magnetic resonance (CW-ODMR), which provides a spin resonance frequency spectrum that can be used to determine temperature. − Now, the CW-ODMR successfully measures slight changes in temperature in cells. The direct current magnetic field is evaluated by measuring the precession of the spin magnetization using Ramsey fringes, also known as “free induction decay (FID)”. , The pH and radicals in the microenvironment are obtained from the longitudinal relaxation time T1 using inversion recovery (T1 relaxometry). ,, The alternating magnetic field is detected based on the transverse relaxation time T2 using the Hahn echo method or dynamic decoupling (T2 relaxometry). The acquisition of spin resonance frequency spectra is currently the most frequently used method in biomagnetic measurements. The measurement procedure is simple. The frequency is swept while continuously irradiating microwaves. When the NVC is at the nonresonant frequency of the microwaves (off-resonance), the spin population of |0> can go over 80%, , but at the resonant microwave frequency (on-resonance), the spin population of |0> decreases due to spin excitation from |0> to |±1>. The resonance frequency can be obtained by plotting the fluorescence intensity against the applied microwave frequency (this plot is called the “spin resonance frequency spectrum” or simply the “ODMR (Optically Detected Magnetic Resonance) spectrum”). This is because a decrease in fluorescence intensity is observed in the on-resonance state. Since the resonance frequency reflects the energy levels derived from the spin Hamiltonian, where thermal, electric, and magnetic influences enter as distinct termsspecifically through the zero-field splitting, Stark, and Zeeman interactionsthis measurement enables their simultaneous and separate quantification via characteristic features in the ODMR spectrum.

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Nanodiamond with NV centers (NVCs). (a) An illustration of the crystal structure of negatively charged NVCs (NV–) that are ODMR active. (b) A transmission electron micrograph of nanodiamonds with NVCs (NV–). (c) A diagram of the energy levels of NVCs (NV–). The green, red, yellow sinusoidal, and black dashed sinusoidal arrows represent optical excitation, fluorescence emission, microwave excitation and intersystem crossing relaxation, respectively.

2.2. Cell Labeling Using Nanoscale Quantum Biosensors

Cell labeling using nanoscale quantum biosensors can be achieved either by binding them to the cell surface or introducing them into the cell. Peptides and antibodies are effective for cell surface binding. However, there is a concern that nanoscale quantum biosensors may detach during circulation in the body or fail to measure intracellular changes if they remain attached to the cell surface. In such cases, methods that promote cellular uptake of the nanoscale quantum biosensors are employed. Introducing them into cells includes chemical methods that promote spontaneous uptake by coating the nanoscale quantum sensors with cell- penetrating peptides, cationic liposomes, cationic polymer, etc., and physical methods that forcibly introduce them into cells, such as electroporation. At present, the use of chemical methods has made it possible to efficiently introduce nanoscale quantum sensors into all types of cells, including iPS cells and cancer cells. ,,

2.3. Biological Application of Nanodiamonds with NVCs

Physicochemical parameters of the intracellular environment, such as temperature, pH, viscosity, electric field, and magnetic field, are recognized for their critical roles in regulating cell activity. These parameters influence the dynamics and reactivity of biomolecules, thereby affecting vital cellular functions. For instance, the enhanced activity of macrophages and immune cells during fever illustrates the biological impact of elevated cell temperature. Moreover, processes such as cell division, gene expression, protein synthesis, and metabolic activity have been shown to be closely linked to these physicochemical factors, including cell Temperature, pH, viscosity electric field, and magnetic field conditions. , Nanodiamonds containing nitrogen-vacancy centers (NVCs) enable real-time sensing of local viscosity through their translational and rotational diffusion behaviors, as well as magnetic field detection via optical measurement of Zeeman splitting. Their biological utility can be further advanced through wide-field imaging techniques or integration with chip-based microwave architectures, making them promising candidates for high-throughput bioassay platforms. ,

3. Hyperpolarized MRI/NMR

Dynamic nuclear polarization (DNP), one of the quantum operations, improve the intrinsically low-sensitivity magnetic resonance (MR) signals, increasing the sensitivity of MR signals by >10,000-fold and realizing hyperpolarized (HP)-MR metabolic imaging and spectroscopy. , In the Overhauser-type DNP manipulation, metal ions, stable radical compounds, or artificially induced triplet states as a radical resource, such as pentacene, are used as donor electrons for electron spin resonance (ESR), followed by the transfer of the microwave-induced electron spin polarization to the nuclear spins in the guest molecules under a (cryo)­magnetic field with appropriate sample conditions. Rapid dissolution of the solid samples generates liquid-state HP samples, which allow intravenous administration into the body for MR metabolic imaging by directly monitoring the enzymatic conversion of the HP molecular probes to metabolites in the deep parts of the body. ,

3.1. Development of Functional HP Molecular Probes

The development of various functional molecular probes with longer T 1 is a key factor in maximally expanding the utility of dissolution-DNP. Molecular probes with long HP lifetimes and strong tolerances for DNP-NMR/MRI have been increasing. These include intermediates in energy metabolism, amino acids or oligopeptides, pH titrators, metal chelators, redox sensors, etc. − These are biological phenomena or chemical reactions detectable within the time window of HP signal decay. By contrast, trimethylphenyl ammonium (TMPA), a 15N-based biosensor, showed the longest T 1 of over 20 min among the small-molecule HP probes. Generating a functional TMPA derivative will facilitate the sensing or quantification of various biological reactions over a much longer period.

Furthermore, unlike other diagnostic imaging techniques, whose molecular probes principally use radio nuclides as a tracer, HP MR distinguishes nuclear spins as the differences in radio frequency on the spectra are differentiated as chemical shifts. Thus, simultaneous detection of multiple compounds is feasible. Due to the rational design of a diagnostic cocktail of different molecules/metabolites associated with each physiological characteristic, the precise detection of the disease state would be realized.

3.2. Hyperpolarized MRI for Metabolic Imaging: Biological and Biomedical Applications

Glucose metabolism is a fundamental mechanism for maintaining life activities, and recently, glutamine metabolism has gained attention as the secondary metabolic pathway for energy production (Figure ). Abnormalities in metabolic activity and/or flux in both metabolic pathways are highly associated with various diseases before the onset and progression of diseases. Detecting such metabolic changes early could lead to new diagnostic markers and treatment response indicators. Hyperpolarized magnetic resonance imaging (HP-MRI) has emerged as a powerful tool to directly observe these metabolic changes in vivo, offering significant potential for next-generation diagnostics and therapy (termed “metabolotheranostics”).

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A scheme for two major cell energy metabolisms, Glycolysis and Glutaminolysis. ATP, adenosine triphosphate. DHODH, dihydroorotate dehydrogenase. FH, fumarate hydratase. GLS, glutaminase. IDH, isocitrate dehydrogenase. KG, ketoglutaric acid. LDH, lactate dehydrogenase. NAD, nicotinamide adenine dinucleotide. OAA, oxaloacetic acid. PC, pyruvate carboxylase. PDH, pyruvate dehydrogenase. PK, pyruvate kinase. PPP, pentose triphosphate. ROS, reactive oxygen species. SDH, succinate dehydrogenase. TCA, tricarboxylic acid.

Among the 13C-labeled molecular probes, pyruvate, an intermediate in glucose metabolism, is the most promising probe. Pyruvate can be easily hyperpolarized, transported into cells via monocarboxylic acid transporter MCT1, and converted to lactate by cytosolic lactate dehydrogenase (LDH), of which process is enhanced in cancer cells. Clinically, pyruvate has shown safety in humans and is actively used in metabolic imaging studies. ,

Glutamine metabolism, or glutaminolysis, has been focused as an alternative important energy metabolism for providing precursors for ATP and reducing agents such as NAD­(P)H or glutathione (GSH). Glutamine is transported into cells via the ASCT2/SLC1A5 transporter and converted to glutamate in mitochondria by glutaminase (GLS). This pathway supports cancer proliferation and prevents cellular senescence.

Thus, the direct monitoring of this metabolism is worthwhile for glutamine-based life science phenomena and medical studies. To date, [5-13C,4,4-d 2,5-15N]-L-glutamine has been successfully developed for in vivo metabolic imaging using HP-MRI via the dissolution-DNP.

Current HP-MRI technologies have a limited spatial resolution, typically several hundred micrometers, making single-cell analysis challenging. However, DNP-NMR combined with a bioreactor system enables the direct monitoring of metabolisms for cell populations. , The number of cells can be reduced to as few as about 104 cells when integrating with micro coils and microfluid.

Parahydrogen-induced polarization (PHIP) provides a more accessible and cost-effective hyperpolarization method. Unlike DNP, PHIP does not require cryogenic conditions and large equipment. With recent advances in probe chemistry and device engineering, ,, PHIP now supports in vivo metabolic studies and real-time therapeutic monitoring. , Its integration with bioreactors or nanodevices and pseudotissues expands its applicability, enabling high-throughput metabolism analysis without high-field MRI or NMR.

3.3. DNP at Room Temperature with Nanocomposites and Material Development

In addition to para-hydrogenation, the hyperpolarization method at room temperature is cryogen-free and is a cost-effective and sustainable approach. These include nanodiamonds, silicon nanoparticles or nanowire , and triplet-DNP.

Recent developments in materials chemistry have overcome some technical drawbacks of DNP. HYbrid Polarizing SOlids (HYPSO) can provide DNP solutions at room temperature after preparation of HP molecular probes in cryogenic dissolution-DNP. , HYperPOlarizing Polymer (HYPOP) materials are being developed to realize actual room temperature hyperpolarization. Recently, using triplet DNP method, cocrystalline matrices with pentacene have successfully polarized biological molecular probes such as urea by transferring polarization of photoexcited triplet state of pentacene. Both HYPOP and HYPSO technologies are crucial for advancing MR applications, particularly in medical diagnostics and drug discovery.

4. Quantum Effects in Biological Systems: From Photosynthesis, Magnetoreception and Catalysis

Biological environments are inherently noisy, with thermal fluctuations and molecular interactions disrupting delicate quantum states. How organisms utilize quantum effects in the warm, humid environments of biological systems, where dissipation and decoherence readily occur, remains an enigma. Recent advancements in quantum biology have revealed intriguing quantum effects in three key biological processes: photosynthesis, magnetoreception, and catalysis. These findings offer exciting possibilities for developing novel biomimetic sensors and quantum-inspired technologies.

4.1. Quantum Coherence in Photosynthetic Light Harvesting

The initial process of photosynthesis, where light-harvesting protein complexes convert light into electron excitation energy, has been one of the main subjects of quantum biological research. Quantum beats corresponding to 1 ps order were reported in the bacteriochlorophyll-containing FMO protein from green sulfur bacteria. Subsequent experiments have suggested that the quantum beats are not derived from the electronic coherence and originate from impulsively excited vibrations. Another study for the PSII reaction center suggests a possibility of mixture of electronic and vibrational coherence, i.e., vibronic coherence. Recent cryo-electron microscopy studies of a phycobilisome from red algae reveal a massive molecular complex containing over 2000 pigments, connecting photochemical reaction centers across 90 nm distances. Thus, they are attracted as a model system to understand the energy transfer mechanism, particularly the achievement of nearly 100% efficiency of energy transfer. Two-dimensional electronic spectroscopy shows the existence of ultrafast energy transfer with a rate constant of less than 100 fs at the top of a phycobilisome of cyanobacteria. This result suggests the possibility of quantum-assisted directional energy transfer. In addition, the rod-shaped regions of phycocyanin molecules create different energy levels, forming a stepwise gradient toward the core region composed of allophycocyanin molecules. These observations hint at the possibility of quantum effects playing a role in the remarkable efficiency of photosynthetic light harvesting. However, further research is needed to elucidate the nontrivial mechanisms and their potential applications in artificial light-harvesting systems.

4.2. Quantum-Based Magnetoreception in Animals

Cryptochromes are proteins that are thought to play a key role in sensing extremely weak magnetic fields (ca. 10s of μT) in various organisms, particularly in birds and some other animals. The proposed sensing mechanism involves a quantum process called radical pairs that are generated upon blue light absorption with the cofactor and tryptophan residues within the molecule. The ratio of triplet and singlet radical pairs is influenced by this weak magnetic field and is believed to be essential for animals to orient themselves using Earth’s magnetic field. The coherence effect of electron spins continues longer than that of photosynthesis because of the nature of the low energy of the electric spin. The interplay between quantum coherence, entanglement, and signal transduction in animal magnetoreception remains an exciting area of research.

4.3. Insights from Hydrogenase Enzymes

Hydrogen, as a carbon-free gaseous fuel, is one of the most promising energy carriers for future energy alternatives to fossil fuels. In aiming for a hydrogen-based economy, hydrogenase (H2ase) enzymes have emerged as potential catalysts for hydrogen production, storage, and utilization. , The metalloenzymes, found in diverse microorganisms, catalyze the reversible oxidation and evolution of H2 in their energy metabolism. Depending on the active site metal cofactors, the enzymes are divided into three main types: [NiFe]-H2ases, [FeFe]-H2ases, and [Fe]-H2ases. The elucidation of H2ase crystal structures since 1995 has been pivotal in advancing their biotechnological applications. [NiFe]-H2ases, with their preference for H2 oxidation over proton reduction, show potential use as electrocatalysts in hydrogen fuel cells. , Conversely, [FeFe]-H2ases, biased toward proton reduction, are being investigated for light-induced H2 evolution devices. , However, their sensitivity to oxidation remains a significant challenge, , prompting extensive research into oxygen-tolerant variants.

4.4. Biomimetic Catalysts and Quantum Effects

In enzyme catalysis, quantum tunneling in the transfer of protons or electrons contributes to reaction efficiency. Building on this understanding, we focus on developing synthetic catalysts that mimic hydrogenase (H2ase) active sites. Recent focus for this protein has shifted from reproducing the primary coordination of each active site to assembling diverse model compounds and regulating secondary coordination spheres in metal complexes. , Of particular interest is the role of diphosphine ligands containing pendant amines, installed in a bis­(diphosphine)nickel complex as inspired by [FeFe]-H2ases. The pendant amines, positioned in the secondary coordination sphere of the metal center, can serve as proton relays in the reversible electrochemical H2 oxidation. This suggests the role of a strictly conserved Arg residue in the active sites of [NiFe]-H2ases, but it remains to be elucidated how the side-chain guanidinium group contributes to the catalytic reaction. ,

Iron–sulfur clusters in [FeFe]- and [NiFe]-H2ases are essential for electron transfer relays connecting the active site metal complex and an external electron donor or acceptor. Recent studies have revealed that hydrogen bonding of a serine hydroxyl group with the [4Fe–4S]H portion of the H-cluster (six-iron active site) in an [FeFe]-H2ase can affect its redox potential. , Furthermore, neutron structural analysis of a [NiFe]-H2ase in its oxidized state has identified an unusual hydrogen bond in the secondary coordination sphere of the proximal iron–sulfur cluster, where the amide proton appears delocalized between the hydrogen bond donor and acceptor atoms (Figure ). This unusual hydrogen bond is speculated to modulate the redox potential of the cluster. Quantum chemical calculations would be beneficial for understanding its formation mechanism and its relationship to the electron transfer.

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How close can neutron diffraction bring us to the understanding of catalysis via quantum mechanical processes? The background of the picture is the measured neutron diffraction pattern. The nickel (green) and iron (brown) ions of the active site in [NiFe]-H2ase along with the iron and sulfur (yellow) ions of the proximal iron–sulfur cluster, are depicted as spheres (PDB code: 8W6X90). The white mesh represents a neutron scattering length density, highlighting the delocalized amide proton.

The quantum nature of proton transfer or electron transfer reactions in H2ases presents an exciting frontier in quantum biology. The mechanisms underlying directional and efficient transfer via quantum tunneling are not fully understood. , Elucidating these quantum effects could provide crucial insights for developing more efficient synthetic catalysts.

5. Future Perspective

The development of nanoscale quantum sensors is progressing across the boundaries of different fields such as physics, chemistry, biology and engineering, and they are attracting attention in various fields due to their recent dramatic development and progress. In particular, the development of cell imaging and sensing technology using nanoscale quantum sensors has made it possible to measure in real time physical and chemical parameters that reflect cell conditions such as intracellular temperature and pH, which were previously difficult to measure. This is expected to lead to the practical application of pharmaceuticals using cells and the elucidation of complex biological phenomena. Furthermore, if the application of cell imaging and sensing is further accelerated, it is expected to bring about innovative contributions not only to pharmaceutical science, but also to a wide range of medical fields, including regenerative medicine, cancer treatment, embryology, immunology, and neuroscience.

The field of hyperpolarized (HP) NMR/MRI is evolving rapidly. While current HP applications require large, specialized facilities, the horizon holds promise for more accessible technologies. Benchtop-sized HP machines, sophisticated microfluid devices and innovative materials are poised to overcome existing technical limitations. These advancements could democratize HP-NMR/MRI research, potentially revolutionizing diagnostic technology and drug discovery. Real-time metabolic analysis using HP-NMR could shed light on emerging biological phenomena, such as biomolecular condensates and metabolic enzyme assemblies. Moreover, the advent of high efficiency hyperpolarizers opens up new possibilities in metabolomics, enabling the detection of metabolites without nuclear labeling. , For widespread use, we have to realize scalability and cost-effectiveness of manufacturing high-quality quantum sensors/HP NMR/MRI. The transformation of laboratory-level prototypes into commercially viable and affordable devices remains a significant challenge.

As our understanding of quantum biological phenomena grows, so too does our ability to develop quantum-inspired nanotechnologies, such as efficient solar energy capture and conversion technologies, applications in medical imaging, geophysical surveying, navigation, and the design of robust quantum devices. By bridging quantum biology and nanotechnology, we can develop sensors and devices that operate on entirely new principles, potentially revolutionizing fields from energy harvesting to medical diagnostics without using chemicals or genetic manipulation.

This paper was supported by the MEXT Quantum Leap Flagship Program (MEXT Q-LEAP, JPMXS0120330644).

The authors declare no competing financial interest.

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