Quantum spin resonance in engineered proteins for multimodal sensing

Nature 649, 1172-1179 (2026) · DOI: 10.1038/s41586-025-09971-3

License: CC BY 4.0.

Abstract

Sensing technologies that exploit quantum phenomena for measurement are finding increasing applications across materials, physical and biological sciences. Until recently, biological candidates for quantum sensors were limited to in vitro systems, had poor sensitivity and were prone to light-induced degradation. These limitations impeded practical biotechnological applications, and high-throughput study that would facilitate their engineering and optimization. We recently developed a class of magneto-sensitive fluorescent proteins including MagLOV, which overcomes many of these challenges. Here we show that through directed evolution, it is possible to engineer these proteins to alter the properties of their response to magnetic fields and radio frequencies. We find that MagLOV exhibits optically detected magnetic resonance in living bacterial cells at room temperature, at sufficiently high signal-to-noise for single-cell detection. These effects are explained through the radical-pair mechanism, which involves the protein backbone and a bound flavin cofactor. Using optically detected magnetic resonance and fluorescence magnetic-field effects, we explore a range of applications, including spatial localization of fluorescence signals using gradient fields (that is, magnetic resonance imaging using a genetically encoded probe), sensing of the molecular microenvironment, multiplexing of bio-imaging and lock-in detection, mitigating typical biological imaging challenges such as light scattering and autofluorescence. Taken together, our results represent a suite of sensing modalities for engineered biological systems, based on and designed around understanding the quantum-mechanical properties of magneto-sensitive fluorescent proteins.

Figures

30 panels with data across 6 figures. Each panel page shows the plot, its columns and its files; each data.csv begins with a header naming the paper, the panel, the source, the license and the provenance route.

Fig. 1

• panel (c-1): Top strip of printed panel (c): the magnet state (0 = off, 1 = on) against time (s), the field switched between 0 mT and 10 mT with a 20 s period, over the 80 s of the single-cell trace in c-2. data.csv
• panel (c-2): Main axes of printed panel (c): magnetic-field effect $\Delta\mathcal{I}/\mathcal{I}_\mathrm{off}$ (%) of a single cell expressing MagLOV 2 against time (s), as the field is switched between 0 mT and 10 mT with a 20 s period (timing in c-1). data.csv
• panel (d): ODMR of MagLOV 2 at a static field $B_0$ of about 21.6 mT: $\Delta\mathcal{I}/\mathcal{I}_\mathrm{bg}$ (%) against frequency (MHz), which decreases left to right as printed. Markers are data from a single cell; the blue line and shaded band are the mean and standard deviation of all cells in the field of view. The micrograph inset of the printed panel is not shown. data.csv
• panel (e): ODMR spectra at $B_0$ = 19.25, 20.28, 21.3, 22.48 and 23.75 mT against frequency (MHz), each offset to a baseline at its $B_0$, markers with fitted curves. The blue line is $\bar{\gamma}_e B_0$ ($g_e = 2.00$), its band the field uncertainty. Each spectrum has its own color, not black with red fits as printed, and the short printed resonance markers are not drawn. data.csv

Fig. 2

• panel (a-1): Magnetic-field effect of AsLOV2 R2: $\Delta\mathcal{I}/\mathcal{I}_\mathrm{off}$ (%) against time (s) over one 20 s cycle of a $B_0 = 10$ mT field, off for the first 10 s and on for the second. Markers are the average over periods, the band the standard deviation; the red curve is the exponential fit, $\tau = 5.85$ s. The printed shading of the on half and its labels are not shown. data.csv
• panel (a-2): Magnetic-field effect of MagLOV: $\Delta\mathcal{I}/\mathcal{I}_\mathrm{off}$ (%) against time (s) over one 20 s cycle of a $B_0 = 10$ mT field, off for the first 10 s and on for the second. Markers are the average over periods, the band the standard deviation; the red curve is the exponential fit, $\tau = 2.02$ s. The printed shading of the on half and its labels are not shown. data.csv
• panel (a-3): Magnetic-field effect of MagLOV 2: $\Delta\mathcal{I}/\mathcal{I}_\mathrm{off}$ (%) against time (s) over one 20 s cycle of a $B_0 = 10$ mT field, off for the first 10 s and on for the second. Markers are the average over periods, the band the standard deviation; the red curve is the exponential fit, $\tau = 2.43$ s. The printed shading of the on half and its labels are not shown. data.csv
• panel (a-4): Magnetic-field effect of MagLOV 2 fast: $\Delta\mathcal{I}/\mathcal{I}_\mathrm{off}$ (%) against time (s) over one 20 s cycle of a $B_0 = 10$ mT field, off for the first 10 s and on for the second. Markers are the average over periods, the band the standard deviation; the red curve is the exponential fit, $\tau = 1.07$ s. The printed shading of the on half and its labels are not shown. data.csv
• panel (b-1): On-resonance ODMR response of AsLOV2 R2: $\Delta\mathcal{I}/\mathcal{I}_\mathrm{off}$ (%) against time (s) over one 20 s cycle of the RF field at $B_0 = 21.6$ mT, off for the first 10 s and on for the second. Markers are the average over periods, the band the standard deviation; the red curve is the exponential fit, $\tau = 3.44$ s. The printed on-half shading and labels are not shown. data.csv
• panel (b-2): On-resonance ODMR response of MagLOV: $\Delta\mathcal{I}/\mathcal{I}_\mathrm{off}$ (%) against time (s) over one 20 s cycle of the RF field at $B_0 = 21.6$ mT, off for the first 10 s and on for the second. Markers are the average over periods, the band the standard deviation; the red curve is the exponential fit, $\tau = 0.46$ s. The printed on-half shading and labels are not shown. data.csv
• panel (b-3): On-resonance ODMR response of MagLOV 2: $\Delta\mathcal{I}/\mathcal{I}_\mathrm{off}$ (%) against time (s) over one 20 s cycle of the RF field at $B_0 = 21.6$ mT, off for the first 10 s and on for the second. Markers are the average over periods, the band the standard deviation; the red curve is the exponential fit, $\tau = 1.32$ s. The printed on-half shading and labels are not shown. data.csv
• panel (b-4): On-resonance ODMR response of MagLOV 2 fast: $\Delta\mathcal{I}/\mathcal{I}_\mathrm{off}$ (%) against time (s) over one 20 s cycle of the RF field at $B_0 = 21.6$ mT, off for the first 10 s and on for the second. Markers are the average over periods, the band the standard deviation; the red curve is the exponential fit, $\tau = 1.36$ s. The printed on-half shading and labels are not shown. data.csv

Fig. 3

• panel (a): Normalized emission spectra with 450 nm excitation, intensity (a.u.) against wavelength (nm), for AsLOV2 R2, MagLOV, MagLOV 2 and MagLOV 2 fast cell suspensions, smoothed with a moving average of 1 nm bandwidth. data.csv
• panel (b): Change of emission intensity between $B_0 = 10$ mT and 0 mT, $\Delta\mathcal{I}$ (counts), against wavelength (nm) for AsLOV2 R2, MagLOV, MagLOV 2 and MagLOV 2 fast, smoothed with a moving average of 1 nm bandwidth. data.csv
• panel (c): Normalized excitation spectra for 510 nm emission, intensity (a.u.) against wavelength (nm), for AsLOV2 R2, MagLOV, MagLOV 2 and MagLOV 2 fast cell suspensions. data.csv
• panel (d): Ultraviolet-visible absorption spectra of purified MagLOV 2 fast, absorbance (OD) against wavelength (nm), at 0, 80 and 180 min after the onset of blue LED illumination. The dashed literature reference spectra of the printed panel are not shown; its inset is the panel d-inset. data.csv
• panel (d-inset): Inset of printed panel (d): the same three absorption spectra of MagLOV 2 fast (0, 80 and 180 min) over the reduced window of about 451 to 750 nm and 0 to 0.04 OD. The dashed literature reference spectra of the printed inset are not shown. data.csv

Fig. 4

• panel (b): Histograms of the timescale $\tau$ (s) fitted to the magnetic-field effect of each cell, counts for the AsLOV R5 and MagLOV 2 populations measured separately, overlaid. data.csv
• panel (c): Histograms of the fitted timescale $\tau$ (s) for an equal mixture of the two populations, counts for the cells classified as AsLOV R5 and as MagLOV 2, overlaid. The printed bars sit half a bin left of those in panel (b); here both panels use the same bin centres. data.csv
• panel (f-1): Normalized intensity at 450 nm (a.u.) against time (s) for one trench of positive-control cells (MagLOV with mCherry): five single cells (gray), the trench average (black) and the applied field, switched between 0 and 10 mT. data.csv
• panel (f-2): Normalized intensity at 450 nm (a.u.) against time (s) for one trench of negative-control cells (EGFP only): five single cells (gray), the trench average (black) and the applied field, switched between 0 and 10 mT. data.csv
• panel (g-1): Classification of single cells: lock-in values (a.u.) against normalized intensity at 565 nm (a.u.), for mCherry negative (EGFP only, green crosses) and mCherry positive (MagLOV, red circles) cells. The gray dashed lines are the control decision (vertical) and the lock-in decision (horizontal). data.csv
• panel (g-2): Classification of trenches: lock-in values (a.u.) against normalized intensity at 565 nm (a.u.), for mCherry negative (EGFP only, green crosses) and mCherry positive (MagLOV, red circles) trenches. The gray dashed lines are the control decision (vertical) and the lock-in decision (horizontal). data.csv
• panel (h): Histogram of the standard deviation of lock-in values between the cells of each trench, $\sigma$(Lock-in values) (a.u.), in counts. The red dashed line is $\sigma$ across all cells. The printed bars are scaled as a density although the axis reads Counts; here they are counts. data.csv

Fig. 5

• panel (e): Lock-in ODMR normalized signal against $z$ position (mm) along the coil axis for two samples of MagLOV 2 fast cells measured separately: raw measurements of Sample 1 (red) and Sample 2 (blue), and gray shaded profiles after deconvolution. data.csv
• panel (f): Lock-in ODMR normalized signal against $z$ position (mm) along the coil axis with both samples of MagLOV 2 fast cells in place at once: the raw measurement (red) and the gray shaded profile after deconvolution. data.csv

Fig. 6

• panel (a): Magnetic-field effect $\Delta\mathcal{I}/\mathcal{I}_\mathrm{off}$ (%) of purified MagLOV 2 fast against [Gadobutrol] (M), three fields of view per concentration (open circles), with the fit $1/(ax+b)+c$. The two cartoon insets of the printed panel and its magenta markers linking three points to panel (b) are not shown. data.csv
• panel (b-1): Printed panel (b), trace 1 of 3 from the top: magnetic-field effect $\Delta\mathcal{I}/\mathcal{I}_\mathrm{off}$ (%) of purified MagLOV 2 fast against time (s) at [Gadobutrol] = $4.41\,\mu$M, magnet on for the first 20 s and off after the dashed line. The printed gray shading of the on half, its labels and the magenta marker are not shown. data.csv
• panel (b-2): Printed panel (b), trace 2 of 3 from the top: magnetic-field effect $\Delta\mathcal{I}/\mathcal{I}_\mathrm{off}$ (%) of purified MagLOV 2 fast against time (s) at [Gadobutrol] = $44.1\,\mathrm{m}$M, magnet on for the first 20 s and off after the dashed line. The printed gray shading of the on half, its labels and the magenta marker are not shown. data.csv
• panel (b-3): Printed panel (b), trace 3 of 3 from the top: magnetic-field effect $\Delta\mathcal{I}/\mathcal{I}_\mathrm{off}$ (%) of purified MagLOV 2 fast against time (s) at [Gadobutrol] = $415\,\mathrm{m}$M, magnet on for the first 20 s and off after the dashed line. The printed gray shading of the on half, its labels and the magenta marker are not shown. data.csv

Cite

Gabriel Abrahams et al. (16 authors). Quantum spin resonance in engineered proteins for multimodal sensing. Nature 649, 1172-1179 (2026). https://doi.org/10.1038/s41586-025-09971-3

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