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Superconducting Mass Spectrometry and Molecule Analysis

Periodic Reporting for period 3 - SuperMaMa (Superconducting Mass Spectrometry and Molecule Analysis)

Okres sprawozdawczy: 2022-07-01 do 2023-06-30

Over the last decades, mass spectrometry has developed into an essential tool for science and a world market worth several billion dollars.
Mass spectroscopy has become a tool for all analytical sciences from fundamental physics, over applied chemistry, biology, pharmacy and clinical medicine to geology and planetary research.

Two grand challenges have, however, remained open throughout all these years:
the detection of slow macromolecular ions with low charge and the analysis of neutral massive macromolecules in the gas phase.

Mass spectrometers rely on the capability to prepare, select and detect molecular ions and many instruments detect these ions via secondary electron multiplication (SEM).
It has been a notorious challenge to efficiently detect massive biopolymers because SEM requires ions at high impact velocities.
Novel applications can therefore profit form detectors that can report the presence of particles with high mass-to-charge ratio and low energy, efficiently.

Moreover, established methods usually do not detect or analyze neutral macromolecular beams.
A novel detector, that provides this feature, can become open a new window for research and technology.

This detector should have a high spatial and temporal resolution, it should have a high detection quanutm yield even for low particle energies independent of the particle composition, and it should be scalable to many pixels - to develop a novel camera.

Protein analysis often is interested in conformations, which also depend on the molecular charge state. Most mass spectrometers handle highly charged molecules, and
new opportunities can open for charge-reduced or even neutral species in high vacuum.

Controlling the charge state of complex biomolecuar systems has been a grand challenge - and a great goal. Important progress hinges on the capability to control the charge softly and in high vacuum.
The synthesis of specific tags, that can be generically bound to complex proteins and cleaved off by laser light at a well defined position and time, addresses this challenge.

Neutral biomolecules in high vacuum have been hardly accessible so far. Novel sources and detectors now open research into this vast material class.
• Superconducting nanowire detector (SNWD or SSPD), a quantum sensor which
a) … can detect massive protein ions at energies even below 50 eV.
b) … can detect continuously, as required to fit to quadrupole or sector field mass spectrometry.
c) … exhibits fast time resolution, compatible with time-of-flight mass spectrometry.
d) … can detect neutral atoms, molecules and clusters down to kinetic energies of a few eV.
e) … enables ‘super’-resolution

• Superconducting camera for particles, such as atomic and protein ions, which
a) … is realized with 8 pixels and room temperature electronics.
b) … is achieved with to 16 pixels, with analogue cryogenic electronics.
c) … is made of 32 pixels, 20 connected to room temperature electronics.
d) … is made up of 128-pixel SNWD pixels, using integrated cryogenic electronics.

• Synthetic and photochemistry technologies, which
a) … allow the synthesis of photo-active tags for 532 nm.
b) … allow demonstrating photo-cleavage of proteins at 532 nm in mass spectrometry.
c) … allow the synthesis of photo-active tags for 355 nm.
d) … allow demonstrating photo-cleavage of proteins at 355 nm in mass spectrometry.
e) … allow the chemical synthesis of dual-color photo-active tags for 355 nm & 532 nm.
f) … explore photo-cleavage of dual-color photo-active tags in mass spectrometry
.
• Mass spectrometry technologies, that
a) … enable quadrupole mass selection for up to 47 kDa/charge.
b) … allow to prepare biomolecular beams compatible with these parameters using charge reduction.

• System integration of source, selection, detection and laser beam techniques, to
a) … detect protein ions at low energy using superconducting nanowire detectors.
b) … demonstrate protein beam profilometry.
c) … detect the internal energy of atoms.
d) … detect electronic energy of molecules.
e) … explore ‘action free’ few-photon absorption spectroscopy on solvent-free biomolecules.
f) … explore profilometry of mass-selected molecular beams using a 128 SNWD array (camera)
Our superconducting nanowire detection experiments are the first report SNWD enhanced quadrupole mass spectrometry and this in a range that is usually not readily accessible to such instruments.

Our fabrication techniques and cryogenic electronics allow preparing arrays of 128 pixels which are readily suited for mass spectrometry and ion beam profilometry in an energy range that has not been accesible to prior instruments based on secondary electron multiplication.

Our photocleavage studies are among the few to explore charge control of large proteins in high vacuum and we can do this with soft green photons, outside of any competition with heating UV bands in complex biomolecules.

The combinatio of these techniques offers new avenues for mass analysis, molecular spectroscopy, atom imaging, quantum interferometry and more.
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