Active Cells, Biochemistry & Physiology Physics & Astronomy

Instrument Development: A lab-scale soft X-ray microscope for biological systems

In plain English

AI plain-English summary

A new microscope will use laser-driven X-rays to capture nanoscale images of living, wet biological samples without damaging them. Current high-resolution imaging techniques often require samples to be dried, frozen, or stained with artificial dyes, which can alter or destroy the very structures scientists want to study. This instrument overcomes that limitation by operating in the "water window"—a specific X-ray wavelength range where water is transparent but carbon (the backbone of organic molecules) absorbs strongly. The system generates coherent X-rays through high harmonic generation, a process that uses intense short laser pulses, then reconstructs images algorithmically without needing lenses. If successful, the microscope will achieve more than ten times better spatial resolution and faster data acquisition than the team’s current 29-nanometre system. It will allow researchers to observe cellular machinery in its natural, hydrated state for the first time at this scale. The instrument will be built as a reliable lab-scale facility, complementing larger synchrotron-based X-ray sources at Harwell and the Central Laser Facility. This could accelerate discoveries in cell biology, drug delivery, and disease mechanisms by providing routine access to nanoscale imaging that currently requires scarce, multimillion-pound national facilities.

View original technical description
This instrument development application proposes the construction of a laboratory based, laser driven, water window x-ray microscope, capable of label free, nanometre spatial resolution, of biological samples with minimal sample damage. The system makes use of the coherent nature of the x-ray radiation generated by high harmonic generation (HHG) from intense short pulse laser pulses. The coherent radiation is the basis of lensless imaging using algorithmic phase reconstruction (e.g. Coherent Diffraction Imaging and Ptychography). The project builds on the current 29 nm imaging systems developed at Southampton and using recent advances in reliable fibre based laser technologies and in line with the Rosalind Franklin Institutes aims, will produce a system with more than an order of magnitude increase in both spatial resolution, data acquisition time, and enable the imaging of hydrated samples with minimal sample damage. The system will be tested with several collaborations and in conjunction with the RFI and Harwell Research Complex imaging capabilities, and will be engineered to become a reliable facility to complement existing capabilities at the Central Laser Facility

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Researchers

Angus Kirkland (Co-Investigator)Emma Springate (Co-Investigator)Jeremy Frey (Principal Investigator)Peter Horak (Co-Investigator)William Brocklesby (Co-Investigator)

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Original classification

Research and Innovation

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