Determination of Matrix Metalloproteinase 2 in Biological Samples Using a 3D Stochastic Microsensor Based on Graphene Oxide/AuNanoparticles/(Z)-N-(pyridin-4-yl-methyl) Octadec-9-enamide.

The levels of the MMPs in the biological samples of confirmed patients with gastric cancer are significantly elevated compared to those found in healthy people. Therefore, a novel 3D stochastic microsensor based on graphene oxide, modified with gold nanoparticles and (Z)-N-(pyridin-4-yl-methyl) octadec-9-enamide (namely N2-AuNP/GO), was designed for the determination of MMP-2 in biological samples, and validated for the screening tests of biological samples in order to be used for the early diagnosis of gastric cancer. The proposed sensor presents a low limit of quantification (1.00 × 10-22 g mL-1), high sensitivity (1.84 × 107 s-1 g-1 mL), and a wide working concentration range (1.00 × 10-22-1.00 × 10-7 g mL-1). Recovery values higher than 99.15% were recorded for the assay of MMP-2 in whole blood, gastric tissue tumors, saliva, and urine samples.

Stochastic Microsensors Based on Carbon Nanotubes for Molecular Recognition of the Isocitrate Dehydrogenases 1 and 2.

Two three-dimensional (3D) stochastic microsensors based on immobilization of protoporphyrin IX (PIX) in single-walled carbon nanotubes (SWCNT) and multi-walled carbon nanotubes (MWCNT) decorated with copper (Cu) and gold (Au) nanoparticles were designed and used for the molecular recognition of isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) in biological samples (brain tumor tissues, whole blood). The linear concentration ranges obtained for the molecular recognition and quantification of IDH1 and IDH2 were: IDH1 (1 × 10-5-1 × 102 ng mL-1) and IDH2 (5 × 10-8 - 5 × 102 ng mL-1). The limits of quantification obtained using the proposed microsensors were: 10 fg mL-1 for IDH1 and 5 × 10-3 fg mL-1 for IDH2. The highest sensitivities were obtained for the microsensor based on MWCNT. High recoveries versus enzyme-linked immunosorbent assay (ELISA) standard method were recorded for the assays of IDH1 and IDH2, all values being higher than 99.00%, with relative standard deviations (RSD) lower than 0.10%.

Disposable stochastic sensors obtained by nanolayer deposition of copper, graphene, and copper-graphene composite on silk for the determination of isocitrate dehydrogenases 1 and 2.

Three disposable stochastic sensors designed using nanolayer deposition of copper (Cu), graphene (GR), and copper-graphene (Cu-GR) composite on the silk textile, as substrate, were modified with chitosan (n=371-744), for biomedical analysis. Isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) served as model analytes for molecular recognition and quantification in biological samples such as whole blood and brain tumor tissue samples. The best sensitivities (3.77×107s µg mL-1 for IDH1, and 1.88×107s µg mL-1 for IDH2) and the lowest limits of quantification (10-2fg mL-1 for IDH1, and 5×10-2fg mL-1 for IDH2) for both IDH1 and IDH2 were recorded for the disposable stochastic sensors based on chitosan/graphene nanolayer. Very good correlations between the screening method based on disposable stochastic sensors and enzyme-linked immunosorbent assay (ELISA) were obtained; this was also proved by the results obtained using the paired t-test.

Sensitive Detection of Heregulin-α from Biological Samples Using a Disposable Stochastic Sensor Based on Plasma Deposition of GNPs-AgPs' Nanofilms on Silk.

A composite material comprised of graphene nanoplatelet and silver particles (GNPs-AgPs) was used for the deposition of GNPs-AgPs' nanofilms with cold plasma on silk. α-Cyclodextrin was used as a modifier of the active surface of the disposable sensor. The disposable stochastic sensor was used in screening tests for the assay of heregulin-α in whole blood and tissue samples. The disposable stochastic sensor showed a low limit of determination (4.10 fg mL-1) and can be used with high sensitivity on a wide concentration range (4.10 fg mL-1-0.04 µg mL-1). The screening method was validated against ELISA when good correlations (confirmed also by the t-test) were obtained.

Fast screening test for molecular recognition of levodopa and dopamine in biological samples using 3D printed stochastic microsensors.

The simultaneous assay of levodopa and dopamine is essential for diagnosis and treatment of neurodegenerative diseases and brain cancer. 3D stochastic microsensors based on multi-walled carbon nanotubes (MWCNTs), gold nanoparticles (AuNPs) and 1-adamantyloleamide (AOA) was used for the simultaneous molecular recognition of levodopa and dopamine in biological samples (whole blood, urine, and brain tissue). The proposed 3D stochastic microsensors presented low limits of quantification, and high sensitivities. High selectivity was recorded versus neurotransmitters such as epinephrine, norepinephrine, serotonin, and glutamate. High recoveries were obtained for the assay of both levodopa and dopamine in whole blood, urine, and tumor tissue samples.

Stochastic microsensors for the assessment of DNA damage in cancer.

Three stochastic microsensors based on graphite powder modified with three different oleamides: N-(2-piperidin-1-ylethyl)oleamide, N-(3,4-dihydroxyphenethyl)oleamide and N-(2-morpholinoethyl)oleamide, were designed, characterized, and used to assess DNA damage in cancer by assaying two biomarkers namely 8-nitroguanine and 8-hydroxy-2'-deoxyguanosine. The two biomarkers were determined from urine and whole blood samples. The characterization of the microsensors was done at two pHs 7.40 and 3.00. The best microsensor for the simultaneous determination of biomarkers in whole blood and urine samples was the one based on the graphite paste modified with N-(3,4-dihydroxyphenethyl)oleamide. The results indicated that the proposed microsensors can be reliably used for pattern recognition and quantitative determination of 8-nitroguanine and 8-hydroxy-2'-deoxyguanosine in whole blood and urine, and accordingly, for the assessment of DNA damage in cancer patients.

Stochastic sensors designed for assessment of biomarkers specific to obesity.

Two stochastic sensors based on the following oleamides: 1-adamantyloleamide and N,N-dimethyl-N-(2-oleylamidoethyl)amine physically immobilized on graphite paste were designed. The sensors were able to determine simultaneously from the whole blood of Wistar rats three biomarkers specific to obesity: leptin, interleukin-6 (IL-6) and plasminogen activator inhibitor 1 (PAI-1). The whole blood samples were obtained from Wistar rats treated with oleoylethanolamide (OEA), (Z)-N-[(1S)-2-hidroxy-1-(phenylmethyl) ethyl]-9octadecenamide (OLA), and with the aqueous solution of 1% Tween 80 used as solvent for oleamides formulations (control samples). The proposed sensors were very sensitive and reliable for the assay of obesity biomarkers in whole blood of rats.