A specialised tiny needle for real-time in vivo deep tissue measurements
Opportunity
Raman spectroscopy is a non-destructive analytical technique that can provide information about the structure and composition of substances at the molecular level. It is a vibration-based, label-free technique that involves illuminating the target material with a laser and analyzing the light scattered from the sample.
In essence, the laser’s photons probe chemical bonds in a substance and interact with their molecular vibrations, resulting in the energy of the laser photons being shifted up or down. This energy shift yields information about the vibration frequencies in the system. Since molecular groups have unique frequencies, the spectrum generated from these vibrations can be used to identify the substance. Because Raman spectroscopy is both efficient and non-destructive, it is used in a wide scope of fields from material engineering to medical sciences.
In medicine particularly, Raman spectroscopy is used in cell and tissue characterization and label-free diagnosis. In fact, recent technology has allowed the development of fibre optic Raman endoscopic probes that can perform in vivo Raman measurements in internal organs, like the stomach and lungs, under endoscopic guidance.
However, these Raman probes usually have an outer diameter of 0.7 to 2 mm and are considered bulky. As such, they can only pass through the large biopsy needles, limiting their use for deep tissue measurements in fine needle aspiration biopsy (FNAB) where channels have an inner diameter less than 0.5mm.
Technology
The novel technology developed to fill this gap is a submillimetre fibre optic Raman needle probe. Unlike previous Raman probes made using multiple fibres and a flat lens, this new design utilises a single multi-mode fibre tapered with a semi-spherical lens to ensure maximum laser excitation and Raman signal collection.
Using a customised Raman spectroscopy system, the researchers demonstrated that using the novel Raman needle probe with in-house-developed background rejection algorithms resulted in high quality tissue Raman measurements.
With adjustments to the dimensions of the new probe and lens, light was optimally focused onto the samples. This allowed the tapered fibre needle probe to improve the overall Raman photon collection by up to 3 times compared to the conventional flat tip Raman fibre probe. Using an improved Raman spectra post-processing algorithm, the researchers also found that the tapered probe has improved depth capability compared to the flat tip probe.
Since this deep-tissue capability was validated in a two-layer oesophageal tissue model, the tapered Raman probe was also tested in other tissue types. This resulted in the tapered Raman probe yielding unique Raman features and peaks that showed the unique biomolecular structure and makeup of the different samples, confirming that it can be used in different tissue types, including skin, muscle, fat and brain. Moreover, the novel probe can effectively collect the signal from the important regions of the Raman spectra within sub-seconds from each other, indicating its effectiveness in collecting real-time data from multiple organ sites.
The submillimetre fibre optic Raman needle probe is tapered with a semi-spherical lens that has a radius of about 125 µm. The needle probe can be easily inserted into a 24G syringe needle for deep tissue collection, and coupled with a Raman spectroscopy system to measure its performance.
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