Disposable Stochastic Miniplatforms for Simultaneous Recognition and Determination of Vitamins B5, B7, and B9 in Food and Pharmaceutical Compounds.

Vitamins are essential for supporting daily physiological functions and are crucial for metabolic processes, including preventing vascular events and delaying the progression of diabetic nephropathy. The specific assessment of food and pharmaceutical compound quality requires the highly sensitive evaluation of vitamins B5, B7, and B9. Therefore, it is necessary to have a fast screening method for multivitamin tablets, pharmaceutical tablets, water, food, including raw egg yolk, and biological fluids, including urine, in order to ensure the precise identification and measurement of vitamins B5, B7, and B9. This paper introduces a novel disposable stochastic miniplatform that utilizes an incorporated 2D stochastic sensor to be able to simultaneously assay the three vitamins. Cobalt-phthalocyanine was used to modify the carbon film of the 2D sensor. High sensitivities (of 102-108 s-1 g-1 mL magnitude order) and low detection limits (of pg mL-1 magnitude order) were recorded for the disposable stochastic miniplatforms. The validation procedure involved the utilization of pharmaceutical tablets, supplement tablets, water samples, food samples, including raw egg yolk, and biological samples, specifically urine. The disposable stochastic miniplatforms demonstrate cost-effectiveness and suitability for the fast screening tests, with a time frame of 6 min, across a range of samples, a capacity of over 150 measurements, and an endurance of up to one month. Recovery values higher than 94.00% with RSD (%) values lower than 1.00 were recorded.

Simultaneous Assay of CA 72-4, CA 19-9, CEA and CA 125 in Biological Samples Using Needle Three-Dimensional Stochastic Microsensors.

Two-needle 3D stochastic microsensors based on boron- and nitrogen-decorated gra-phenes, modified with N-(2-mercapto-1H-benzo[d]imidazole-5-yl), were designed and used for the molecular recognition and quantification of CA 72-4, CA 19-9, CEA and CA 125 biomarkers in biological samples such as whole blood, urine, saliva and tumoral tissue. The NBGr-2 sensor yielded lower limits of determination. For CEA, the LOD was 4.10 × 10-15 s-1 g-1 mL, while for CA72-4, the LOD was 4.00 × 10-11 s-1 U-1 mL. When the NBGr-1 sensor was employed, the best results were obtained for CA12-5 and CA19-9, with values of LODs of 8.37 × 10-14 s-1 U-1 mL and 2.09 × 10-13 s-1 U-1 mL, respectively. High sensitivities were obtained when both sensors were employed. Broad linear concentration ranges favored their determination from very low to higher concentrations in biological samples, ranging from 8.37 × 10-14 to 8.37 × 103 s-1 U-1 mL for CA12-5 when using the NBGr-1 sensor, and from 4.10 × 10-15 to 2.00 × 10-7 s-1 g-1 mL for CEA when using the NBGr-2 sensor. Student's t-test showed that there was no significant difference between the results obtained utilizing the two microsensors for the screening tests, at a 99% confidence level, with the results obtained being lower than the tabulated values.

New stochastic devices for simultaneous analysis of mismatch repair proteins and KRAS in biological samples.

Two stochastic microsensors based on the immobilization of inulins: inutec and frutafit in a paste obtained from a graphene decorated with nitrogen (10.8 %), and boron (2.6 %), and paraffin oil (IR purity) were designed, characterized and validated for the molecular recognition and analysis of mismatch repair proteins like MLH1, MSH2, MSH6, PMS2, and of KRAS in biological samples such as: whole blood, urine, saliva, and tumoral tissues. The sensor based on inutec exhibited the largest working concentration range (10 decades of concentration) and the lowest limit of determination (0.32fg mL-1) when used for the assay of MLH1, and the wider working concentration range (8 decades of concentration), and the lowest limit of determination (2.30fg mL-1) when used for the assay of MSH6. The sensor based on frutafit exhibited the largest working concentration range (10 decades of concentration) when used for the determination of KRAS, and the wider working concentration range (5 decades of concentration), and the lowest limit of determination (1.00fg mL-1) when used for the assay of PMS2. No influence of the modifier (inutec and frutafit) was recorded on the linear concentration range (10 decades of concentration), and on the limit of determination (1.00 fg mL-1) for the assay of MSH2. The recoveries of MLH1, MSH2, MSH6, PMS2, and of KRAS in whole blood, urine, saliva, and tumoral tissues were higher than 98.00 with RSD (%) values lower than 0.10 %.

Bioanalysis of MMR and KRAS - a key factor in diagnosis of colorectal cancer.

Two miniaturized electrochemical devices were designed for the simultaneous bioanalysis of MMR (MLH1, MSH2, MSH6, PMS2), and of KRAS in whole blood, urine, saliva, and tumoral tissues. The devices comprised besides the electronic part of the potentiostat a combined 3D stochastic microsensor (combined microplatform) with the sensing part based on the modification of graphene decorated with nitrogen, sulfur and boron (NSB-EGR) modified with two types of frutafit: FTEX and FHD. For the assay of MSH2, MSH6, KRAS, and PMS2 higher sensitivities were recorded when the microdevice based on FHD was used, while for the assay of MLH1 the best sensitivity was achieved by using the microdevice based on FTEX. While the limits of quantification for MLH1, MSH2, and PMS2 were not influenced by the modifier, the microdevice based on FHD provided the lowest limit of quantification for KRAS, the microdevice based on FTEX provided the lowest limit of quantification for MSH6. The validation tests performed proved that recoveries of MLH1, MSH2, MSH6, PMS2, and of KRAS in whole blood, urine, saliva, and tumoral tissues higher than 98.50% with RSD (%) values lower than 0.10% were recorded.

Nanoplatform-based analysis for the detection of HER3 and HER4 for gastric cancer diagnosis.

Nanographene andα-cyclodextrin based sensors modified with gold nanoparticles and spheroidal copper were used to develop two stochastic sensors, which were then characterized and validated for the purpose of molecularly identifying and quantifying HER3 and HER4 in biological samples. In order to accomplish this goal, each of the stochastic sensors was incorporated in a nanoplatform. The two nanoplatforms were connected to a smartphone and recorded very low limits of determination (1 × 10-15g ml-1) and wide linear concentration ranges (1 × 10-15-1 × 10-8g ml-1) when a potential of 170 mV versus Ag/AgCl was applied. This allowed for the molecular identification and quantification of HER3 and HER4 in patients with gastric cancer, as well as in healthy individuals.

Molecular Recognition and Quantification of HER-3, HER-4 and HRG-α in Whole Blood and Tissue Samples Using Stochastic Sensors.

Human epidermal growth factor receptor-3, human epidermal growth factor-receptor-4, and heregulin-α are some of the biomarkers related to gastric cancer currently being used for early detection, personalized treatment, and evaluation of the efficiency of the treatment. Two stochastic sensors based on graphene decorated with TiO2 and/or Au modified with maltodextrin were proposed for the screening of two types of whole blood and tissue samples for the simultaneous recognition and analysis of the three biomarkers. The sensitivity of the two sensors showed high values, whereas the limits of determination were of fg mL-1 magnitude order. Thus, the proposed screening method can perform the quantitative analysis of both of the biomarkers of interest in whole blood and tissue samples, with recoveries higher than 96.00% and relative standard deviations lower than 1.00%.

Carbon Nanopowder-Based Stochastic Sensor for Ultrasensitive Assay of CA 15-3, CEA and HER2 in Whole Blood.

Two microsensors obtained by the physical immobilization of 5,10,15,20-tetraphenyl-21H,23H-porphine (TPP) and 5,10,15,20-tetrakis (pentafluorophenyl chloride)-21H,23H-iron (III) porphyrin (Fe(TPFPP)Cl) in carbon nanopowder decorated with gold nanoparticles (AuNp) were designed, characterized, validated and used for the molecular recognition and simultaneous ultrasensitive determination of CEA, CA15-3 and HER2 in whole blood. High sensitivities were recorded for both microsensors. Low limits of quantification were recorded for all biomarkers: CEA (12.8 pg mL-1 by using Fe(TPFPP)Cl/AuNp, and 190 fg mL-1 by using TPP/AuNp), CA 15-3 (100 fU mL-1 for both microsensors) and HER2 (3.9 fg mL-1 by using Fe(TPFPP)Cl/AuNp, and 35 fg mL-1 by using TPP/AuNp). A very good correlation between the results obtained using the proposed microsensors and ELISA, certified by the Student t-test, proves that the screening test can be used for ultrasensitive assays of the three biomarkers in whole blood.

N,S-Decorated graphenes modified with 2,3,7,8,12,13,17,18-octaethyl-21H,23H-porphine manganese(III) chloride-based 3D needle stochastic sensors for enantioanalysis of arginine: a key factor in the metabolomics and early detection of gastric cancer.

Arginine has an important role in the metabolomics of gastric cancer. Two 3D enantioselective needle stochastic sensors based on the physical immobilization of 2,3,7,8,12,13,17,18-octaethyl-21H,23H-porphine manganese(III) chloride (solution, 10-3 mol L-1) in graphene paste matrices decorated with N and S atoms were designed, characterized and validated for the enantioanalysis of arginine in whole blood and tissue samples. The signature values obtained for the enantiomers of arginine confirmed that the stochastic sensors are enantioselective. The lowest limit of quantification obtained for both enantiomers of arginine was 1 fmol L-1, while sensitivity of up to 1011 s-1 mol-1 L was recorded for the stochastic sensors. High recoveries were obtained for the determination of one enantiomer in the presence of the other one; moreover, very good correlation was found between the results obtained with the two 3D enantioselective needle stochastic sensors.

Interleukin-8, CXCL10, CXCL11 and their role in insulin resistance in adult females with subclinical hypothyroidism and prediabetes.

In obesity, the hormonal secretion of the thyroid gland switches from homeostasis to type 2 allostasis in order to adapt to persistent modifications of adipose tissue and inflammation. Previous meta-analyses have linked obesity with an increased risk of developing thyroid diseases, prediabetes, and type 2 diabetes mellitus. We designed an observational cross-sectional study including all female patients presenting consecutively in an ambulatory clinic for 16 months. This study aimed to describe the level of serum cytokines and chemokines in relation to TSH, fT4 and insulin resistance (IR) indexes in patients with subclinical hypothyroidism (SCH). The study included 72 women with a median age of 59 ± 17.75 years, and a mean BMI (Body Mass Index) of 31.48 ± 6.75 kg/m2. Modelling homeostasis model assessment of IR indices (HOMA-IR) based on chemokines (IL-8, CXCL10, CXCL11, leptin), C-reactive protein, the presence or absence of SCH, taking into account age, BMI, abdominal circumference, glycated haemoglobin (HbA1c), and anti-thyroid peroxidase antibodies (ATPO) as covariates, identified a single chemokine that was significantly associated with the dependent variable (IL-8). IR indices are negatively associated with IL-8 in female patients with subclinical hypothyroidism, but the effect of the cytokine is minimal. BMI rather than TSH influences the level of CXCL11 in our population. CXCL10 has a tendency to increase in patients with SCH, obesity and prediabetes, with no association with TSH.

Fast screening method for early diagnostic of gastric cancer based on utilization of a chitosan - S-doped graphene - based needle stochastic sensors.

Needle stochastic sensors were developed for the assay of carbohydrate antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA) in different biological samples (e.g., whole blood, tissues, urine, and saliva). Sulfur doped graphene powders were modified with chitosan; paraffin oil was added to form a homogeneous paste that was used as active side of the stochastic sensors. High sensitivities and low limits of determination were achieved for the assay of CA19-9 and CEA in biological samples. The validation of the proposed screening method (which is utilizing the stochastic sensors as screening tools) was made by using real biological samples obtained from confirmed patients with gastric cancer; very good correlations for the concentrations of CEA and CA19-9 were obtained using the needle stochastic sensors.

Stochastic microsensors based on modified graphene for pattern recognition of maspin in biological samples.

Maspin is a novel serine protease inhibitor differentially expressed in several types of human cancers. It proved to be a key biomarker in the assessment of gastric cancer. Therefore, we design, characterize, and validate two stochastic microsensors based on graphene co-doped with N and S, and modified with α-cyclodextrin and maltodextrin, for the pattern recognition and quantification of maspin in whole blood, gastric tumor tissue, saliva, and urine. While the sensitivities were comparable with magnitude order, the variations were in the wideness of the linear concentration range, when measurements were performed at a pH of 7.40. Very low limits of quantification were recorded at both working pHs: 7.40, and 3.00. High recoveries of maspin in whole blood, gastric tissue tumor, saliva, and urine were also recorded.

Mini-Review: Electrochemical Sensors Used for the Determination of Water- and Fat-Soluble Vitamins: B, D, K.

Vitamins are one of the most essential organic compounds that are necessary for the human body, in order to develop and grow in a healthy way. The aim of this mini-review is to bring together a series of electrochemical sensors (voltametric and amperometric) developed for the determination of vitamins from the families of B, D and K in biological, pharmaceutical or food-related samples. For this mini-review, 16 articles published between 2016 and 2021 were taken into consideration.

2D disposable stochastic sensors for molecular recognition and quantification of maspin in biological samples.

Three disposable stochastic sensors using nanolayer deposition of a graphene nanocomposite comprising graphene nanoparticles and gold nanoparticles, on different supports: silk, plastic, and paper, and modified with chitosan, were characterized and validated for molecular recognition and quantification of maspin in biological samples. Very low limits of determination (of pg mL-1 magnitude order) were recorded (5.12 pg mL-1 for the sensor based on silk at pH 7.40 and on copy paper at pHs 3.00 and 7.40; 16 ng mL-1 at pH 7.40 for the sensor based on plastic, 41.00 pg mL-1 for the sensor based on silk at pH 3.00, and 204.00 pg mL-1 for the sensor based on plastic, at pH 3.00), with wide linear concentration ranges (5.12 × 10-12-2.00 × 10-6 g mL-1 for the sensors based on silk at pH 7.40, and on copy paper at pH 3.00; 5.12 × 10-12-8.00 × 10-7 g mL-1 for the sensor based on copy paper at pH 7.40; 1.60 × 10-8-2.00 × 10-6 g mL-1 for the sensor based on plastic at pH 7.40; 4.10 × 10-14-2.00 × 10-6 g mL-1 for the sensor based on silk, at pH 3.00; and 2.04 × 10-13-8.00 × 10-7 g mL-1 for the sensor based on plastic at pH 3.00) allowing the molecular recognition and quantification of maspin in healthy people and patients with gastric cancer, when a potential of 125 mV vs. Ag/AgCl was applied. The recoveries of maspin in whole blood, saliva, urine, and tissue samples were higher than 95.00%, with a relative standard deviation lower than 1.0%.

Smart Portable Device Based on the Utilization of a 2D Disposable Paper Stochastic Sensor for Fast Ultrasensitive Screening of Food Samples for Bisphenols.

Since the determination of the high toxicity of bisphenol A, alternative structures for bisphenols have been synthesized, resulting in bisphenols C, E, F, S, and Z. These bisphenols have replaced bisphenol A in plastic bottles, toys, and cans used for preserving food. Later, the toxicity and negative effects of all of these bisphenols on people's health were proven. Therefore, there is a need for a fast ultrasensitive screening method that is able to detect the presence of these bisphenols in any condition directly from food samples. This paper presented a disposable device based on the utilization of a 2D disposable paper stochastic sensor for the fast ultrasensitive screening of food samples for bisphenols A, C, E, F, S, and Z. The 2D disposable sensor was obtained by the deposition of graphene and silver nanolayers on paper using cold plasma. Furthermore, the active side of the sensor was modified using 2,3,7,8,12,13,17,18-octaethyl-21H,23H Mn porphyrin. The limits of quantification of these bisphenols were 1 fmol L-1 for bisphenols C and E, 10 fmol L-1 for bisphenols A and F, 10 pmol L-1 for bisphenol S, and 1 pmol L-1 for bisphenol Z. The recoveries of these bisphenols in milk, canned fruits, vegetables, and fish were higher than 99.00% with RSD (%) values lower than 1.50%.

Gold Nanoparticles/Nanographene-Based 3D Sensors Integrated in Mini-Platforms for Thiamine Detection.

Vitamins are essential for sustaining daily activities and perform crucial roles in metabolism, such as preventing vascular events and delaying the development of diabetic nephropathy. The ultrasensitive assessment of thiamine in foods is required for food quality evaluation. A mini-platform utilizing two 3D sensors based on nanographene and gold nanoparticles paste modified with protoporphyrin IX and protoporphyrin IX cobalt chloride is proposed for the detection of thiamine in blueberry syrup, multivitamin tablets, water, and a biological sample (urine). Differential pulse voltammetry was utilized for the characterization and validation of the suggested sensors. The sensor modified with protoporphyrin IX has a detection limit of 3.0 × 10-13 mol L-1 and a quantification limit of 1.0 × 10-12 mol L-1, whereas the sensor modified with protoporphyrin IX cobalt chloride has detection and quantification limits of 3.0 × 10-12 and 1.0 × 10-11 mol L-1, respectively. High recoveries (values greater than 95.00%) and low RSD (%) values (less than 5.00%) are recorded for both 3D sensors when used for the determination of thiamine in blueberry syrup, multivitamin tablets, water, and urine, demonstrating the 3D sensors' and suggested method's high reliability.

Stochastic biosensors based on N- and S-doped graphene for the enantioanalysis of aspartic acid in biological samples.

Metabolomics plays a very important role in cancer mechanism and also in the early diagnosis of cancer. The enantioanalysis of aminoacids found in biological samples may favor the development of new screening tests for the early diagnosis of cancer. Two stochastic biosensors, based on the immobilization of α-hemolysin and hemin in exfoliated reduced graphene modified with nitrogen and sulphur, were proposed for the enantioanalysis of aspartic acid in biological samples (whole blood, urine, saliva, and tissue). The proposed biosensors showed low limits of quantification, high sensitivity, and large linear concentration ranges. The recoveries of d- and l-aspartic acid in biological samples were higher than 95.00%, with a relative standard deviation lower than 1.00%.

Fast Screening of Whole Blood and Tumor Tissue for Bladder Cancer Biomarkers Using Stochastic Needle Sensors.

Bladder cancer is one of the most common urologic malignancies, which is more frequent in men than in women. The early diagnosis for this type of cancer still remains a challenge, therefore, the development of a fast screening test for whole blood and tumor tissue samples may save lives. Four biomarkers, p53, E-cadherin, bladder tumor antigen (BTA), and hyaluronic acid were considered for the screening tests using stochastic needle sensors. Three stochastic needle sensors, based on graphite powder and modified with three types of chitosan, were designed and characterized for the screening test. The proposed sensors showed low limits of quantification, and high sensitivity and selectivity levels. The recoveries of p53, E-cadherin, BTA, and hyaluronic acid in whole blood samples and tissue samples were higher than 95.00% with a relative standard deviation lower than 1.00%.