Abstract
To exploit the full potential of the transverse spatial structure of light using the Laguerre–Gaussian basis, it is necessary to control the azimuthal and radial components of the photons. Vortex phase elements are commonly used to generate these modes of light, offering precise control over the azimuthal index but neglecting the radially dependent amplitude term, which defines their associated corresponding transverse profile. Here, we experimentally demonstrate the generation of high-purity Laguerre–Gaussian beams with a single-step on-axis transformation implemented with a dielectric phase-amplitude metasurface. By vectorially structuring the input beam and projecting it onto an orthogonal polarization basis, we can sculpt any vortex beam in phase and amplitude. We characterize the azimuthal and radial purities of the generated vortex beams, reaching a purity of 98% for a vortex beam with l =50 and p = 0. Furthermore, we comparatively show that the purity of the generated vortex beams outperforms those generated with other well-established phase-only metasurface approaches. In addition, we highlight the formation of “ghost” orbital angular momentum orders from azimuthal gratings (analogous to ghost orders in ruled gratings), which have not been widely studied to date. Our work brings higher-order vortex beams and their unlimited potential within reach of wide adoption.
Keywords: vortex beams, Laguerre−Gaussian beams, phase-amplitude metasurfaces, orbital angular momentum
Introduction
The ability to structure light in all
its transverse degrees of
freedom has led to advances in fundamental science and real-world
applications, both classical and quantum.1 Particularly significant and utile are vortex light beams, which
carry orbital angular momentum (OAM).2 Since
they are associated with a vortex phase of the form
,3 azimuthal
phase elements have become ubiquitous for their generation, from spiral
phase plates4 and computer-generated holograms
displayed on spatial light modulators (SLM),5 to the use of geometric phase elements such as liquid crystals,6−8 or they can be created directly at the source.9,10 Recently,
a resurgence in vortex generation approaches has emerged with the
advent of nanofabrication,11 moving away
from traditional bulky optical components to subwavelength-structured
planar devices that shape the wavefront of light in all its properties,
i.e., amplitude, phase, and polarization.
The ease of use and ability to control polarization and phase in metasurfaces have facilitated the realization of many well-established metasurface devices for optical vortex generation, including q-plates12 and their notable generalization J-plates.13 However, as with other phase-only devices, they approximate a vortex beam by an incident Gaussian beam modulated by an azimuthal phase profile and subsequently neglect the amplitude term, which defines the annular intensity associated with these modes. As a consequence, the generated beam is not a solution to the paraxial wave equation and thus not an eigenmode of free space. During its propagation, the beam unravels, leading to the excitation of many undesirable radial modes.14 An example of a resulting impure vortex mode, with its many concentric rings of intensity, is depicted in Figure S4. This phenomenon has been shown to have a deleterious effect on the detection efficiency in both classical and quantum OAM applications,15 the implication of which becomes increasingly prominent for beams carrying larger OAM.
To ensure the invariance associated with
eigenmodes during their
propagation, the generated vortex beams must be generalized solutions
of the paraxial wave equation. Many families of transverse solutions
to the paraxial wave equation exist. In cylindrical coordinates, the
solutions form a complete, orthonormal basis, called Laguerre–Gaussian
(LG) modes of light. These modes require a pair of independent indices
to fully describe them: the azimuthal and radial indices,
and p. LG beams have garnered
much attention because of their circular symmetry, the infinite Hilbert
space they provide, and their inherent relation to the quantization
of orbital angular momentum (OAM).16 They
are natural modes of quadratic index media,17 making them a viable candidate for free space and optical fiber
communication. Their transverse structure is given by18
| 1 |
where ω0 is the beam waist,
is the generalized Laguerre polynomial
of argument x, and r and ϕ
are the radial and azimuthal coordinates, respectively. The azimuthal
component,
, is related to a vortex phase profile ψ(ϕ),
which results in a “twist” of the wavefront and quantizes
the OAM of
per photon.3 On the other hand, the radial component, p, is
related to the transverse amplitude distribution
, which results in “ripples”
in the beam intensity. Although neglected in the past, radial modes
have attracted interest for their diffraction properties as a means
to control light propagation in complex media.19,20 Recent work has also explored using the radial component as an additional
encoding space for quantum21,22 and classical information
protocols.23,24
To have control over the azimuthal and radial indices, we need to be able to modulate not only the phase of the incident beam but also its amplitude. One approach is to use an active resonator to facilitate the mode conversion necessary for generating pure OAM modes,25,26 but this requires elaborate cavity configurations. Alternative free-space methods have also been demonstrated, which employ complex amplitude modulation using phase-only devices.27 This involves carving the amplitude of the incident beam and discarding the remainder in an unwanted drop-port. The common practice is to use a spatial drop-port, as shown in Figure 1a, in which a linear grating diffracts the desired spatial profile, leaving the unwanted amplitude on the main optical path, which can be spatially filtered using an aperture. The drawback of this method is that it requires working off-axis with a diffraction order. Nanostructured silica glass devices have also been proposed to produce pure vortex beams.28 However, the devices are restricted to using circularly polarized incident fields, with their practical demonstration being limited to generating vortex beams with low OAM values.29,30 On the other hand, vortex beams of high OAM charge and purity have been generated using a two-step process, which combines the high resolution of metasurfaces with complex amplitude modulation achieved using a spatial light modulator to correct for the missing amplitude term.15
Figure 1.

(a) Spatial drop-port, implemented via a grating, is used to carve the amplitude of the incident beam and discard the remainder in a drop-port that can be spatially filtered. (b) Phase-amplitude metasurfaces allow for an alternative approach using polarization as a drop-port. By vectorially structuring the incident beam and projecting it onto an orthogonal polarization state (λ–), the desired amplitude can be revealed.
Here, using polarization as a drop-port, we experimentally
demonstrate
a generalized method for generating LG modes of high radial and azimuthal
purity, which we achieve using a single dielectric metasurface—called
the p-plate, since it addresses p-modes.31 The device’s ability
to structure light vectorially allows an arbitrary input beam to be
modulated in phase and amplitude32,33 (after a projection
onto the orthogonal polarization state) using a single on-axis transformation,
as shown in Figure 1b. We refer to such a combination as a phase-amplitude metasurface.32 The compact device also has the advantage that
it can be structured as an annular device without sacrificing performance,
enabling the fabrication of larger devices while reducing the write
time for electron-beam lithography. It follows that the total structured
area of the device is inversely proportional to the OAM it imparts
(see Figure S5). This results in a reduction
in the structured area of up to 75% for a device designed to impart
a charge of
. Overall, we experimentally show that our
device can generate modes with well-defined radial and azimuthal purities,
albeit with a simple and practical approach that is readily employable
in flat-optics systems, from imaging to quantum applications.
Results and Discussion
Ripple-Free Vortex Beams with High Topological Charge
The metasurface device is designed to impart an azimuthal phase, as well as a radially varying polarization transformation that converts part of the incident beam to the orthogonal polarization state. The resulting beam is a vector vortex beam that carries OAM and exhibits a nonuniform polarization distribution. A polarizer, either implemented as a separate element or as a wire-grid grating integrated into the metasurface substrate,33 can then be used to select the orthogonal polarization and effectively filter out the excess amplitude and any unconverted light.
An example of a fabricated p-plate device used to generate a pure LG10,0 vortex mode is shown in Figure 2a. The metasurface device consists of many rectangular nanopillars, with the birefringence of each pillar arising from its form factor. Specifically, the desired azimuthal phase profile ψ(ϕ) defines one of the two dimensions of the pillar Lx(ϕ), while the other dimension Ly(ϕ) is determined by ψ(ϕ) + Δϕ0, where Δϕ0 is a fixed parameter that corresponds to the phase retardance required to perform the desired polarization conversion to the orthogonal state.31 The desired amplitude profile, in this case A10,0(r) (purple line in the inset of Figure 2a), is sculpted from the incident Gaussian amplitude A0,0(r) (yellow line) according to an amplitude transmission function T(r) (red line). The transmission function is assimilated in the rotation angle of the pillars, α0(r), to employ a radially varying polarization conversion, which, upon the projection onto an orthogonal state, attenuates the incident amplitude and filters the desired A10,0(r) profile. For example, when the rotation angle of the pillar is α0 = π/4, light undergoes a polarization conversion to the orthogonal state that is not attenuated by the polarizer, resulting in the maximum transmission of light at that point. Conversely, when α0 = 0, light remains in its original polarized state, which is filtered by the orthogonal polarizer, so no light is transmitted. Therefore, since the desired beam has zero intensity at the center, the metasurface can be preemptively patterned to its characteristic annular shape, as the metasurface in this region would not impart a polarization conversion and light would, in any case, be filtered by the polarizer.
Figure 2.
(a) Optical image of
a p-plate metasurface device
designed to generate a pure LG10,0 vortex mode. The insets
show scanning electron microscope (SEM) images of the device, overlaid
with a cross section of the transmission function T(r) (red), which is required to carve the desired A10,0(r) amplitude (purple)
from the incident Gaussian A0,0(r) amplitude (yellow). The transmission function is assimilated
into the angles of the pillars α0, which vary along
the radial direction. Minimum and maximum transmission occur when
α0 = 0 or π/4, respectively. (b) The simulated
vectorial polarization structure of a beam generated directly at the
plane of the p-plate device designed with
and p = 0. The corresponding
experimental near-field intensity distributions of the beam projected
onto the (c) vertical and (d) horizontal polarization states. (e)
The radial p-mode spectrum of the vortex beam generated
by the p-plate compared to the theoretical p-mode spectrum of an azimuthal phase-only approach. The
insets show the corresponding far-field (FF) intensity distributions.
The operating principle of the p-plate allows
it to be designed to impart the required transformations on any incident
wave with known polarization, phase, and amplitude distribution, such
as a plane or Gaussian wave. We designed and fabricated the p-plates to act on a linearly polarized Gaussian beam, as
it is a readily available source in any laboratory. To optimize the
generation efficiency of the device, we design the p-plates for the specific beam waist ωs of the Gaussian
source such that the overlap between the incident intensity profile
and that of the desired intensity profile is maximized. The corresponding
beam waist ω0 of the Gaussian embedded in the target
LG mode is then given by
. We note that in situations where efficiency
can be neglected, this constraint can be lifted by designing the device
for an incident plane wave (see Figure S7). In this way, any beam in the laboratory can be easily extended
to approximate a plane wave, enabling the p-plate
device to work with any readily available source, albeit less efficiently
since the overlap of intensity profiles will be smaller and more light
will be discarded in the drop-port. As a demonstration, we fabricated
another p-plate device designed to modulate a plane
wave, with the corresponding generated mode shown in Figure S7.
To establish the efficacy of the p-plate device
in generating pure vortex modes, we experimentally demonstrate a p-plate that when incident with a Gaussian beam generates
an LG50,0 vortex beam with a charge of
and no radial modes (p = 0). A schematic of the generation and detection experimental setup
is shown in Figure S8. The vectorial structure
of the beam after the metasurface is shown in Figure 2b. Figure 2c,d shows the corresponding experimental near-field
intensity distributions of the generated LG50,0 mode when
projected onto the vertical and horizontal polarization bases, respectively.
The corresponding horizontally polarized component has the characteristic
annular intensity distribution of a vortex mode, while the vertically
polarized component is the unwanted complementary intensity distribution
from which the intensity was carved, leaving behind a dark ring.
To further comment on the purity of the generated vortex beam,
i.e., the spread of its energy among different azimuthal (
) and radial (p) modes,
the generated vortex beam was decomposed onto the
mode basis. We compute the modal overlap
by simply performing the inner product
between the generated vortex beam Ψ(r) and
the conjugate of the desired mode Φ(r) using
an SLM and then extract the modal weighting coefficients
as a quantitative measure of purity. A
vortex beam has a well-defined radial and azimuthal purity when
, i.e., 100% of the power being in the desired
LG mode. The inner product is performed experimentally with the details
described in the Methods section.
In the case of radial mode purity, the generated vortex was decomposed onto the LG50,p basis, with the measured p-mode spectrum shown in Figure 2e. The results confirm a high radial mode purity, with 97% of the generated beam power being in the desired p = 0 mode (see Figure S9 for the azimuthal mode spectrum). The Fourier intensity distribution of the vortex beam after it is propagated to the far-field is shown in the inset. We note that no spatial filtering was employed and that the polarization conversion to the orthogonal state allowed any residual light to be filtered by the polarizer. For comparison, the theoretical p-mode spectrum is also shown for the case when only an azimuthal phase is used to impart such a high OAM. In this case, the power in the desired p = 0 mode drops to 40%, with most of the beam’s energy being spread over higher-order radial modes. Optically, this manifests as concentric rings or radial ripples in the beam’s intensity, as seen in the accompanying inset of Figure 2e.
Comparing Dielectric Metasurfaces for Vortex Beam Generation
Having demonstrated that p-plate metasurfaces
can generate vortex beams with high OAM charges and purity, we experimentally
compare their performance to those of phase-only metasurfaces. As
subjects of the latter, we consider the widely used dielectric metasurfaces, q-plates and J-plates, as vortex beam generators.
The q-plate is a spin–orbit coupling device,
which uses the geometric phase to convert a circularly polarized incident
Gaussian beam to the orthogonal polarization state while imparting
an azimuthal phase. These devices are designed using identical pillars,
which effectively act as half-waveplates and whose orientation angle
varies in azimuth to confer the desired phase profile. On the other
hand, the J-plate, a significant generalization of
the q-plate, decouples the dimensions of the pillars,
combining both propagation and geometric phase control to imbue any
two orthogonal polarization states with independent arbitrary values
of OAM,
and
. Additionally, we judiciously design the J-plates to convert the incident circular polarization to
the orthogonal state with opposite handedness. Therefore, in q-plates and J-plates, the prescribed polarization
conversion allows any residual Gaussian beam to be filtered. In contrast
to p-plate devices, the nanopillars of q-plates and J-plates do not vary in dimension or
orientation angle along the radial direction and as such do not apply
any amplitude shaping. Consequently, for q-plates
and J-plates, the beam waist, ωs, of the incident Gaussian beam determines the beam waist ω0 of the generated LG beam. To ensure a fair comparison, we
fabricated all devices using the same design library and methods as
before. In addition, the characterization of all devices was performed
with the same incident Gaussian beam, so that LG beams carrying the
same OAM had the same beam waist, ω0.
The comparison
between the three types of devices (p-plates, J-plates, and q-plates) used to generate
vortex beams of charges
is presented in Figure 3. Visually, many concentric intensity rings
can be seen in intensity distribution shown in Figure 3b,c and are more apparent for beams carrying
higher OAM. These radial ripples are a consequence of any phase-only
approach that modulates a Gaussian beam by an azimuthal phase. In
contrast, when the radial degree of freedom is controlled as a means
of modulating the amplitude, a single intensity ring appears, as in
the case of the p-plate shown in Figure 3a. Figure 3d–f shows the corresponding p-mode spectra obtained. For p-plate devices
(see Figure 3d), the
power in the desired
mode is greater than 99% for all
modes, indicating high radial mode purity.
The p-mode spectrum of azimuthal phase-only devices
in Figure 3e,f shows
how the mode power is spread over a superposition of higher radial
modes. This effect becomes more pronounced as the OAM increases, with
the power in the desired p = 0 radial mode reaching
only 61 and 66% for the
mode generated using our J-plate and q-plate, respectively. These results
show a clear advantage for using phase-amplitude modulation for vortex
beam generation, particularly for beams with high OAM.
Figure 3.

Experimental far-field
intensity distributions of vortex beams
generated using amplitude and phase control in (a) p-plates and phase-only control in (b) J-plates and
(c) q-plates. For each type of device, three devices
were designed to impart the topological charge
. Corresponding radial p-mode spectra for (d) p-plates, (e) J-plates, and (f) q-plates, obtained via a modal
decomposition in the
basis. We note that no spatial filtering
was used in the generation or detection of the vortex beams.
Ghost Diffraction Orders in Azimuthal Gratings
In the
experimental intensity images shown in Figure 3, we observe azimuthal undulations in the
intensity, reminiscent of a pearl necklace. These “pearls”
are an artifact in vortex beams generated by azimuthal phase gratings
and have remained unnoticed in the literature, despite being present
in previous works.13,15 To understand their origin, we
consider the case of a p-plate whose azimuthal phase
is imparted purely by propagation phase in addition to a polarization
conversion to the orthogonal polarization state (see the Supporting Information for a discussion on J-plate and q-plate devices). The intensity
distribution for an LG5,0 mode generated from a p-plate features
pearls, as shown in Figure 4a. Their azimuthal structure alludes to an
undesirable contribution of OAM, reminiscent of the intensity distribution
of a superposition of interfering vortices of opposite charges,
and
, which similarly form well-defined
petal structures. This is confirmed by
the azimuthal mode decomposition performed on the vortex beams generated
by the p-plate devices for
, as presented by the corresponding spectra
in Figure 4b. Peaks
can be seen at the designed azimuthal index, with up to 97% of the
power of the generated vortex being in the designed
mode. Additional peaks of the order of
a percent are seen at
contributions. Despite being small in contribution,
the interference of these modes constitutes a strong visual effect.
Indeed, unlike superpositions of radial modes, whose intensity profiles
scale with the radial index p, superpositions of
opposite OAM charges lie on the same radius and have a larger overlap.
Figure 4.
(a) Experimental
intensity distribution of a vortex beam generated
by a p-plate with
and p = 0 reveals
azimuthal intensity undulations. (b) The
experimental azimuthal
-mode spectra for vortex beams generated
by p-plates with
. The inset shows small peaks at contributions
of opposite topological charge
, which constitute a strong visual effect
in panel (a). Illustration of the formation of “ghost”
OAM orders as a result of a small deviation in the grating depth,
δ, from 2π (dashed line) to 2π M (shaded area) in
(c) an azimuthal phase-only grating (which maps to a blazed grating
in polar coordinates) and (d) a phase grating with polarization conversion
(as in the p-plate). In both simulations, each device
is designed to impart a topological charge of
. (e) The simulated azimuthal
-mode spectra for vortex beams generated
in panels (c) and (d) showing ghost OAM contributions.
The origin of these superfluous OAM orders dates back to the work of Rowland and Michelson34,35 on false spectral lines produced by ruled gratings, in which ghost orders were described as originating from periodic errors of grating lines, with small error amplitudes resulting in excessively large ghost intensities. We advance the argument that these ghost orders are not limited to linear gratings but are susceptible to any diffraction grating elements, including azimuthal gratings. In the case of the latter, the relation becomes apparent when the azimuthal profile is mapped to polar coordinates, revealing a linear blazed grating (see Figure 4c). It follows then that a small deviation in the grating depth, δ, which in the case of metasurfaces may result from fabrication errors that deviate from the designed pillar size or height, will lead to a cross-coupling of adjunct ghost OAM modes.
To validate their presence, we performed numerical simulations,
in which we show that a small deviation (on the order of 10%) in the
azimuthal grating depth produces the so-called ghost OAM orders. We
consider two cases for generating an
vortex beam. The first applies a phase-only
azimuthal phase (see Figure 4c), which unwraps to a blazed grating with
phase jumps in polar coordinates. The second
applies an azimuthal phase as well as an arbitrary polarization conversion,
as in the case of p-plates (see Figure 4d). In this case, the form
birefringence of the metasurface structure allows each orthogonal
polarization state to be addressed with an arbitrary phase profile.
For p-plates, the azimuthal phase profile seen by
the orthogonal polarization states is the same. This results in an
unwrapped blazed grating with
phase jumps. The presence of ghost OAM
orders, in both cases, is confirmed by the simulated azimuthal modal
spectrum, shown in Figure 4e. For the phase-only approach, ghost OAM orders appear at
multiples of the designed charge
, whereas for the p-plate
device, there is only one appreciable OAM diffraction peak at
. The polarization conversion in the p-plate device results in a cross-coupling of ghost orders
that suppresses their effect, with the OAM orders being spaced by
(see the Supporting Information). In both cases, the contribution at
manifests as the
pearls in the intensity profile of the
vortex beam. Consequently, the numerical result for the p-plate device agrees with the experimental results, in that a small
deviation in the grating depth manifests as small contributions of
ghost OAM orders, with the first OAM diffraction order at
. Nonetheless, we emphasize that although
this is a visually pronounced effect, it corresponds to a very small
contribution of around a few percent. The azimuthal mode purity of
the generated beams is above 97%, which is comparable to the radial
purity results for the same devices.
Conclusions
We have demonstrated the generation of
high-purity vortex beams
from a single metasurface, with complete control of both azimuthal
and radial components. The ability to structure light vectorially
and, therefore, to use polarization as a drop-port provides a compact
on-axis conversion system that is easy to implement in practical flat-optics
systems. Furthermore, the subwavelength resolution of the device allows
for the structuring of pure vortex beams of very high OAM, highlighted
in the demonstration of a vortex beam with an
charge. Our results show the benefit of
using p-plate devices for radial mode purity, which
outperform other well-established vortex-generating metasurfaces (J-plates and q-plates). As such, p-plates could be of interest in any vortex application
in which the radial mode purity cannot be neglected.
The generalized
approach is not limited to pure vortex modes but
rather allows us to harness the full resource of LG modes with any
desired
and p-mode distributions.
In fact, the ability to perform phase and amplitude modulation allows
us to sculpt many other families of paraxial beams. Exploiting the
control over the complete transverse spatial degree of freedom is
significant for the emerging field of high-dimensional quantum information,
boosting communication channels with higher encoding capacities24 and increasing noise robustness in entanglement
distributions.36 We foresee these devices
as a very convenient and powerful approach, which could further drive
the uptake of higher-order vortex modes.
Methods
Metasurface Fabrication
The dielectric metasurface devices consist of amorphous silicon nanopillars on a fused silica substrate, arranged in a hexagonal closed-packed lattice. The metasurfaces are designed to operate in the near-infrared at 1064 nm. A phase library of nanopillars was simulated using a finite-difference time-domain software (Lumerical), together with a complex-value refractive index measured by ellipsometry. The height of each pillar was fixed at 600 nm, while the dimensions and orientation angle of the pillars were allowed to vary to impart a different phase delay between the x and y components of the field (by exploiting form birefringence). This allowed the required transformations to be implemented using either propagation or geometric phase. The fabricated devices are 200 μm in diameter and where applicable are designed to accept a focused Gaussian with a beam waist of 92 μm. Particularly, the p-plate devices were preemptively structured as annular rings by defining the annular region as the region where the intensity transmission function of the device is above 5%.
The fabrication of the metasurfaces proceeded as follows: an a-Si film of 600 nm was deposited onto the fused SiO2 substrate by plasma-enhanced chemical vapor deposition (STS LPX PECVD system). To ensure no charging effects during electron-beam exposure, a 10 nm thick Au film was deposited on top of the poly(methyl methacrylate) layer by physical vapor deposition. The exposure was carried out using a Raith150 Two electron-beam lithography system, with a beam energy of 20 keV and a beam current of 140 pA. A thin layer of Cr was deposited on the sample and then subjected to a lift-off process to reveal a hard mask of the metasurface design. This mask was transferred to the a-Si film using a plasma-enhanced reactive ion etching system (Sentech SI500), which was optimized for etch depth and sidewall verticality.
Measuring the Purity of Vortex Beams
The azimuthal
and radial purities of the generated vortex beams are measured using
a well-established phase flattening approach, called modal decomposition,37 with the idea of unraveling the wavefront into
a Gaussian-like mode. To do this, the generated beam is imaged via
a 4f telescope onto a phase-only SLM (HOLOEYE GAEA-2), on which we
display complex amplitude holograms of the conjugate modes in our
LG basis, as outlined in ref (37). We use the beam waist ω0 of the embedded
Gaussian to define the hologram used in the complex amplitude modulation.
We operate the SLM at the first diffraction order in the reflection
mode, although Figure S8 shows it in transmission
mode for simplicity. We compute the optical overlap by means of a
lens and measuring the Fourier-plane on-axis pixel intensity using
a camera. A pinhole is placed before the camera (Spiricon LT665) to
block unwanted diffraction orders. In this way, we extract the weighting
coefficients
that describe the contribution of each
of the modes in our basis. We employed background subtraction to remove
noise from the acquired intensity images. We note that a combination
of quarter- and half-waveplates (not shown in Figure S8) were used to ensure the correct polarization conversion
in the generation and detection steps.
Supporting Information Available
The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsphotonics.2c01697.
Discussion on the generation of ghost OAM orders by J-plates and q-plates, p-plate conversion efficiency, reduction in the writing area of the p-plate device as a function of the OAM, schematic of the experimental generation and detection setup, and optical images of LG50,0p-plate devices for both plane wave and Gaussian incident waves (PDF)
Author Contributions
⊥ M.d.O. and M.P. contributed equally to this work.
This work was financially supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme “METAmorphoses”, grant agreement no. 817794, and by Fondazione Cariplo, grant no. 2019-3923.
The authors declare no competing financial interest.
Supplementary Material
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