Method development for increased sensitivity of dried-droplet-calibration and cell analysis with LIBS and LA-ICP-MS

Abstract

Laser induced breakdown spectroscopy (LIBS) is a power spectroscopic technique with a wide variety of applications from biomedicine to the metallurgy and mining industry. However, quantitative analysis with LIBS is generally dependent on the availability of certified reference materials or requires the preparation of matrix matched standards. The use of dried droplets offers an alternative calibration approach that is much faster and simpler in preparation. In typical dried droplet calibration, the residue forms a ring-like pattern, referred to as the coffee-ring effect (CRE), which increases the residue size and can induce matrix effects due to the uneven distribution of the analyte. Methods to decrease the residue size by suppressing the CRE and concentrating the analyte on a small area would therefore enhance the signal to noise ratio, reduce the time needed for full ablation and minimize the possibility of matrix effects. In this thesis, the application of a hydrophobic coating to reduce the surface contact area of the droplet and alteration to the pH-value of the droplet solution have been identified as promising ways to generate dried droplet residues that are concentrated on small areas. Additionally, the use of a deep eutectic solvent (DES) was demonstrated to be a potential alternative for carbon calibration with dried droplets, as the DES would form small residues even on unmodified silicon wafer substrates.The developed approach has been applied in the second part of this for the treatment of a hepatic spheroid model with a supramolecular system, consisting of nanoparticles with a therapeutic agent, was investigated in a collaborative effort. Imaging results were obtained via laser ablation inductively coupled plasma mass spectroscopy (LA-ICP-MS) and showed an initial accumulation of nanoparticles at the borders of the spheroid, with diffusion towards the center taking place at later treatment stages. Dried droplet calibration methods, developed in the first part of this thesis, were deployed to obtain quantitative results. These confirmed an increase in nanoparticle absorption by the spheroids, when increasing the treatment concentration. Thus, proving the applicability of dried droplet calibration in a practical analysis setting.