Non-Invasive, Topical Sampling of Potential, Low-Molecular Weight, Skin Cancer Biomarkers: A Study on Healthy Volunteers

Abstract

Monitoring of low-molecular weight cancer biomarkers, such as tryptophan (Trp) and its derivative kynurenine (Kyn), might be advantageous to non-invasive skin cancer detection. Thus, we assessed several approaches of topical sampling of Trp and Kyn, in relation to phenylalanine (Phe) and tyrosine (Tyr), on the volar forearm of six healthy volunteers. The sampling was performed with three hydrogels (made of agarose or/and chitosan), hydrated starch films, cotton swabs, and tape stripping. The biomarkers were successfully sampled by all approaches, but the amount of collected Kyn was low, 20 ± 10 pmol/cm 2 . Kyn quantification was below LOQ, and thus, it was detected only in 20% of topical samples. To mitigate variability problems of absolute amounts of sampled amino acids, Tyr/Trp, Phe/Trp, and Phe/Tyr ratios were assessed, proving reduced inter-individual variation from 79 to 45% and intra-individual variation from 42 to 21%. Strong positive correlation was found between Phe and Trp, pointing to the Phe/Trp ratio (being in the 1.0–2.0 range, at 95% confidence) being least dependent on sampling materials, approaches, and sweating. This study leads to conclusion that due to the difficulty in quantifying less abundant Kyn, and thus the Trp/Kyn ratio, the Phe/Trp ratio might be a possible, alternative biomarker for detecting skin cancers.

Interfacial Self‐assembly of Chiral Selenide Nanomembrane for Enantiospecific Recognition

“…To investigate the detection performance of the ten‐layer (10L) D‐nanomembrane, we analyzed the L‐Kyn level using serum and cerebro‐spinal fluid (CSF) ( n =7) clinical human samples from patients with Alzheimer's disease (AD) and healthy subjects. The concentrations of L‐Kyn in the serum was 1.01±0.27 μM in healthy subjects and 1.56±0.45 μM from patients with Alzheimer's disease, respectively, while the L‐Kyn levels in the CSF for these two groups were 0.12±0.053 μM and 0.17±0.045 μM (Figures 5c and 5d), respectively, as confirmed by liquid chromatography with tandem mass spectrometry (LC/MS/MS) (Tables S5 and S6) [32] . Notably, the sensitivity was approximately two orders of magnitude superior than that of LC/MS/MS (Figure S22), thus, providing capability to monitor Kyn in clinical samples.…”

“…Analysis showed that the ionic current decreased from 39.53±1.43 nA to 4.51±1.87 nA as the concentration of L‐Kyn increased from 10 −8 mM to 10 −1 mM in a linear fashion when using the 10L D‐Se nanomembrane while the ionic current decreased from 39.53 nA±1.43 nA to 38.98±1.65 nA as the concentration of D‐Kyn increased from 10 −8 mM to 10 −1 mM using the 10L D‐Se nanomembrane (Figures 4d and 4e). The linear calibration curve between Kyn concentration and the intensity of the photo‐driven ion current signal was established for the detection of L‐Kyn, with a limit of detection (LOD) of 0.0074 nM for L‐Kyn when using the 10L D‐Se nanomembrane (Figure 4f), with better levels of sensitivity that were ten‐fold higher than previously reported methods (Table S3) [32] . In addition, an LOD of 0.0058 nM for D‐Kyn was achieved by the L‐nanomembrane (Figure S18).…”

“…The linear calibration curve between Kyn concentration and the intensity of the photo-driven ion current signal was established for the detection of L-Kyn, with a limit of detection (LOD) of 0.0074 nM for L-Kyn when using the 10L D-Se nanomembrane (Figure 4f), with better levels of sensitivity that were ten-fold higher than previously reported methods (Table S3). [32] In addition, an LOD of 0.0058 nM for D-Kyn was achieved by the L-nanomembrane (Figure S18).…”

“…The concentrations of L-Kyn in the serum was 1.01 � 0.27 μM in healthy subjects and 1.56 � 0.45 μM from patients with Alzheimer's disease, respectively, while the L-Kyn levels in the CSF for these two groups were 0.12 � 0.053 μM and 0.17 � 0.045 μM (Figures 5c and 5d), respectively, as confirmed by liquid chromatography with tandem mass spectrometry (LC/MS/MS) (Tables S5 and S6). [32] Notably, the sensitivity was approximately two orders of magnitude superior than that of LC/ MS/MS (Figure S22), thus, providing capability to monitor Kyn in clinical samples. Statistical analysis showed that the L-Kyn concentrations of AD patients were higher than those of healthy subjects (Figures 5c, d); this was consistent with previous reports.…”

Photonic Interpenetrating Polymer Network Fibers Comprising Intertwined Solid-State Cholesteric Liquid Crystal and Polyelectrolyte Networks for Sensor Applications

“…Noninvasive sampling offers easy access to physiologically relevant biomarkers with minimum discomfort and supervision . Sweat, tear fluid, saliva, urine, breath, stool, seminal fluid, and swab specimen are the dominant sample types that can be collected noninvasively and analyzed using integrated diagnostic devices. , The analytical instruments used in current scientific studies, such as ion chromatography, electrophoresis, atomic spectroscopy, and mass spectroscopy, are often subject to stringent operating guidelines, delicate sample preparation, and meticulous maintenance. However, these analyses are currently only available in centralized laboratories.…”