Raman technique spots signs of kidney damage

13 Jan 2022

Shanghai team develops noninvasive test for condition of donor organs.

A global shortage of donor kidneys compared to the number of patients in need of a transplant has put added focus on the methods used to assess the quality of candidate organs before transplantation.

Discard rates currently remain high, partly due to the difficulty of precisely measuring the extent of injury or damage suffered by a donor kidney, which has a direct bearing on later patient outcomes.

A project at the University of Shanghai for Science and Technology (USST) has now demonstrated a technique based on Raman scattering that could offer a possible solution, by allowing the detection of biomarkers related to kidney injury in donor organs. The same principle might also be suitable for diagnosis of developing kidney problems in patients.

"Today the lack of methods for precisely measuring donor kidney injury and predicting transplant outcome leads to high discard rates and recipient complications in clinical practice," said Mingxing Sui from Shanghai's Changhai Hospital, a project partner. "We want to solve this problem by developing a new system that can noninvasively provide an objective measure of donor kidney quality."

As reported in Optics Express, the technique is the first use of surface-enhanced Raman scattering (SERS) for simultaneous ultrasensitive detection of secretory leukocyte peptidase inhibitor (SLPI) and interleukin 18 (IL-18), both important biomarkers for kidney damage.

The use of SERS to detect low levels of specific biomarkers has been a topic of research for some time, but for assessment of potential transplant organs one hurdle has been effective methods to amplify the inherently faint Raman signals of interest in specific tissue environments.

Gold or silver nanoparticles are one method of surface enhancement, especially if they can be made to self-assemble into controllable and reproducible hot-spots to boost the SERS response. But the Shanghai project instead employed nanoparticles combining gold with black phosphorus (BP), a more recent candidate for SERS applications known to exhibit excellent optical and biocompatible properties.

Objective assessment of donor organs

Black phosphorus/gold nanohybrids were synthesized by depositing Au nanoparticles onto BP nanosheets, serving as SERS-active substrates. The combination offers a high-density of inherent and accessible hot-spots, according to the project.

"As an approach to SERS analysis BP/Au nanohybrids display high and stable SERS activity, which is crucial for sensitive, quantitative and reliable detection," noted the team in its paper. "SERS fingerprints can readily detect multiple biomarkers in one measurement."

In trials aimed at detecting the biomarkers simultaneously when they were mixed into fetal bovine serum as a model biological environment, the new hybrid SERS substrate showed a reproducible detection limit down to 1.53×10^-8 milligrams per milliliter for SLPI and 0.23×10^-8 milligrams per milliliter for IL-18.

These results indicate the high sensitivity and reliability of the method, said the project, and showed that the SERS-based method holds great potential for use in clinical practice. Future work will involve identifying more biomarkers suitable for kidney assessment, and development of machine learning algorithms to improve the interpretation of the spectral fingerprints.

"This highly sensitive SERS-based multiplexing technique can rapidly capture subtle changes in the biomarker expression levels associated with donor kidney injury," said Mingxing Sui. "This paves the way for objectively assessing the quality of donor kidneys in clinical practice."