Single cell spectroscopy: Noninvasive measures of small-scale structure and function

Mousoulis, Charilaos; Xu, Xianfan; Reiter, David A.; Neu, Corey P.

doi:10.1016/j.ymeth.2013.07.025

Cited by 16 publications

(8 citation statements)

References 130 publications

(136 reference statements)

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“…Furthermore, because the NV ensemble SR sensor is not subject to limitations associated with finite NV coherence time or diffusion-limited sample correlation time, it provides spectral resolution nearly two orders of magnitude narrower than previously demonstrated in NV-detected NMR, enabling observation of J-couplings and chemical shifts for the first time using a solidstate spin sensor. Of particular interest in this picoliter sample-volume regime is the possibility of performing NMR spectroscopy of small molecules and proteins [ 24 ] at the single-cell level. While some work has been done on inductively-detected intracellular NMR with slurries of bacterial cells [ 25 ] and large individual eukaryotic cells such as oocytes [ 26 ], NMR spectroscopy of smaller individual cells has not been achieved.…”

Section: Discussionmentioning

confidence: 99%

High-resolution magnetic resonance spectroscopy using a solid-state spin sensor

Glenn

Bucher

Lee

et al. 2018

Nature

373

454

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Quantum systems that consist of solid-state electronic spins can be sensitive detectors of nuclear magnetic resonance (NMR) signals, particularly from very small samples. For example, nitrogen-vacancy centres in diamond have been used to record NMR signals from nanometre-scale samples, with sensitivity sufficient to detect the magnetic field produced by a single protein. However, the best reported spectral resolution for NMR of molecules using nitrogen-vacancy centres is about 100 hertz. This is insufficient to resolve the key spectral identifiers of molecular structure that are critical to NMR applications in chemistry, structural biology and materials research, such as scalar couplings (which require a resolution of less than ten hertz) and small chemical shifts (which require a resolution of around one part per million of the nuclear Larmor frequency). Conventional, inductively detected NMR can provide the necessary high spectral resolution, but its limited sensitivity typically requires millimetre-scale samples, precluding applications that involve smaller samples, such as picolitre-volume chemical analysis or correlated optical and NMR microscopy. Here we demonstrate a measurement technique that uses a solid-state spin sensor (a magnetometer) consisting of an ensemble of nitrogen-vacancy centres in combination with a narrowband synchronized readout protocol to obtain NMR spectral resolution of about one hertz. We use this technique to observe NMR scalar couplings in a micrometre-scale sample volume of approximately ten picolitres. We also use the ensemble of nitrogen-vacancy centres to apply NMR to thermally polarized nuclear spins and resolve chemical-shift spectra from small molecules. Our technique enables analytical NMR spectroscopy at the scale of single cells.

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Section: Discussionmentioning

confidence: 99%

High-resolution magnetic resonance spectroscopy using a solid-state spin sensor

Glenn

Bucher

Lee

et al. 2018

Nature

373

454

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“…Likewise, improvements in sensitivity and spectral resolution could enable NMR spectroscopy of small molecules and proteins in single cells with potential applications ranging from single-cell metabolomics 134,135 to NMR fingerprinting of tumors. 135,136 Furthermore, the optical read-out of NV-NMR allows for spatial resolution, which can be visualized as ''scanning microscopy'' by moving the laser excitation and thus the measurement volume.…”

Section: Discussionmentioning

confidence: 99%

Advances in nano- and microscale NMR spectroscopy using diamond quantum sensors

2022

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“…Some examples of applications for mass-limited and concentration-limited liquid-state samples that particularly benefit from hyperpolarization include identification of natural products, metabolites of pharmaceuticals and agrochemicals, and characterization of compounds from combinatorial chemistry; , studies of structure and dynamics of membrane proteins and other biomacromolecules that are difficult to isolate and prone to aggregation at the high concentration typically needed for standard NMR measurements; and in-cell NMR. , Such applications require the ability to sense both small volumes and small concentrations. Double-resonant structures provide sample volumes of nanoliters, but the fill factor for the RF part of the double-resonator is very small, resulting in poor sensitivity.…”

Section: Instrumental Challenges and Outlook For Liquid-state Dnp Nmrmentioning

confidence: 99%

Challenges and Advances in the Application of Dynamic Nuclear Polarization to Liquid-State NMR Spectroscopy

Abhyankar

Szalai

2021

J. Phys. Chem. B

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Nuclear magnetic resonance (NMR) spectroscopy is a powerful method to study the molecular structure and dynamics of materials. The inherently low sensitivity of NMR spectroscopy is a consequence of low spin polarization. Hyperpolarization of a spin ensemble is defined as a population difference between spin states that far exceeds what is expected from the Boltzmann distribution for a given temperature. Dynamic nuclear polarization (DNP) can overcome the relatively low sensitivity of NMR spectroscopy by using a paramagnetic matrix to hyperpolarize a nuclear spin ensemble. Application of DNP to NMR can result in sensitivity gains of up to four orders of magnitude compared to NMR without DNP. Although DNP NMR is now more routinely utilized for solid-state (ss) NMR spectroscopy, it has not been exploited to the same degree for liquid-state samples. This Review will consider challenges and advances in the application of DNP NMR to liquid-state samples. The Review is organized into four sections: (i) mechanisms of DNP NMR relevant to hyperpolarization of liquid samples; (ii) applications of liquid-state DNP NMR; (iii) available detection schemes for liquid-state samples; and (iv) instrumental challenges and outlook for liquid-state DNP NMR.

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Single cell spectroscopy: Noninvasive measures of small-scale structure and function

Cited by 16 publications

References 130 publications

High-resolution magnetic resonance spectroscopy using a solid-state spin sensor

High-resolution magnetic resonance spectroscopy using a solid-state spin sensor

Advances in nano- and microscale NMR spectroscopy using diamond quantum sensors

Challenges and Advances in the Application of Dynamic Nuclear Polarization to Liquid-State NMR Spectroscopy

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