TGA/Chemometrics addressing innovative preparation strategies for functionalized carbon nanotubes.

In this work, functionalized carbon nanotubes (CNTs) using two polyamine polymers, polyethyleneimine (PEI) and polyamidoamine dendrimer (PAMAM), were investigated by thermal analysis in order to address preparation strategies to obtain low cytotoxic compounds with the ability to conjugate microRNAs and, at the same time, to transfect efficiently endothelial cells. Thermogravimetric analysis (TGA) was coupled to chemometrics as a novel analytical strategy to characterize functionalized CNTs from different preparation conditions. In particular, two starting materials were considered: very small CNTs and carboxylated CNTs (CNT-COOH) in order to examine the affinity with polymers. Chemometrics permitted to compare results from TGA and to investigate the effect of a number of factors affecting the synthesis of coated nanotubes including a different amount of involved polymer and the time required for the suspension for a satisfactory and reproducible preparation procedure. The results demonstrated the effectiveness of TGA as a tool able to address synthesis of coated CNTs to be employed as efficient drug delivery vectors in biomedical applications.

An Innovative Multilevel Test for Hemoglobinopathies: TGA/Chemometrics Simultaneously Identifies and Classifies Sickle Cell Disease From Thalassemia.

Introduction: Hemoglobinopathies are the most common genetic disorder wordlwide and because of migrations are become an emerging global health problem. Screening programmes for Sickle cell disease and Thalassemia have been implemented in some countries, but are not a common practice, due to a lack in the accuracy of the methods and to the costs of the analyses. Objectives: The objective of this study was the application of the thermogravimetry coupled to chemometrics as new screening method to perform an early diagnosis of thalassemia and sickle cell disease. Methods: Whole blood samples (30 µL) from sickle cell anemia and thalassemia patients were analyzed using the thermobalance TG7 and the resulting curves were compared with those of healthy individuals. A chemometric approach based on Principal Components Analysis (PCA) was exploited to enhance correlation between thermogravimetric profiles and a model of prediction by Partial Least Square Discriminant Analysis (PLS-DA) was developed and validated. Results: The characteristic profile of the blood sample thermal decomposition and the first derivative of the TG curve showed that patients were clearly distinguished from healthy individuals as a result of different amounts of water and corpuscular fraction of blood. The chemometric approach based on PCA allowed a quick identification of differences between healthy subjects and patients and also between thalassemic and sickle cell anemia subjects. Chemometric tools (PLS-DA) were used to validate a model of prediction to process the thermogravimetric curves and to obtain in 1 h an accurate diagnosis. The TGA/Chemometric test permitted to perform first level test for hemoglobinopathies with the same accuracy of confirmatory analyses obtained by the molecular investigation. Conclusions: A screening test based on the coupling of thermogravimetry and chemometrics was optimized for the differential diagnosis of hemoglobinopathies. The novel test is able to simultaneously perform a simple and fast diagnosis of sickle cell anemia or thalassemia, in a single analysis of few microliters of non-pretreated whole blood at low cost, and with high accuracy. Moreover this method results particularly suitable in pediatric patients as it requires small sample volumes and is able to characterize also transfused patients.

Development of a novel test for the identification of hereditary erythrocyte membrane defects by TGA/Chemometrics.

Systematic screening for congenital erythrocyte disorders is not a common practice, due to a lack in the accuracy of the methods and to the costs of the analyses. As a consequence, the diagnosis is usually made when a severe complication occurs. This study introduces an innovative method to perform the screening of a hereditary disease characterized by erythrocyte membrane defects such as hereditary spherocytosis (HS) and hereditary elliptocytosis (HE). Blood samples from healthy donors and patients affected by HS and HE were processed by thermogravimetric analysis (TGA) and the resulting curves were analyzed by chemometrics in order to develop a model of prediction. A novel test was developed and validated by chemometrics and results were found to be in accordance with the genetic diagnosis, confirming the prediction ability of the optimized model that uses few microliters of whole non pretreated blood to perform the diagnosis of HS/HE in less than one hour.

Differential diagnosis of hereditary hemolytic anemias in a single multiscreening test by TGA/chemometrics.

A multi-screening test based on the coupling of thermogravimetry and chemometrics was optimized for the differential diagnosis of hereditary hemolytic anemias. The novel test is able to simultaneously perform a simple and fast diagnosis of sickle cell anemia, thalassemia, hereditary spherocytosis and hereditary elliptocytosis in a single analysis of a few microliters of non-pretreated whole blood. The thermogravimetric profile of blood from patients affected by such disorders was found to be characteristic of a specific anemic status or a disorder due to membrane defects. In addition, chemometric tools were used to validate a model of prediction to process the thermogravimetric curves and to obtain in 1 hour an accurate diagnosis. The effectiveness of the novel test was evaluated by comparing results with the confirmatory analyses specific for each disorder. The TGA/chemometric test made it possible to perform a first level test of congenital erythrocyte defects, including the hemoglobinopathies and disorders due to membrane defects with the same accuracy of confirmatory analyses obtained by molecular investigation. In addition, the novel test was used for the diagnosis of a number of Italian difficult cases, including neonatal patients for which the conventional screening tests did not manage to obtain a diagnosis confirming the high prediction ability of the single multiscreening test.

TGA/Chemometrics addressing innovative preparation strategies for functionalized carbon nanotubes / 药物分析学报

In this work, functionalized carbon nanotubes (CNTs) using two polyamine polymers, polyethyleneimine (PEI) and polyamidoamine dendrimer (PAMAM), were investigated by thermal analysis in order to address preparation strategies to obtain low cytotoxic compounds with the ability to conjugate micro-RNAs and, at the same time, to transfect efficiently endothelial cells. Thermogravimetric analysis (TGA) was coupled to chemometrics as a novel analytical strategy to characterize functionalized CNTs from different preparation conditions. In particular, two starting materials were considered:very small CNTs and carboxylated CNTs (CNT-COOH) in order to examine the affinity with polymers. Chemometrics permitted to compare results from TGA and to investigate the effect of a number of factors affecting the synthesis of coated nanotubes including a different amount of involved polymer and the time required for the suspension for a satisfactory and reproducible preparation procedure. The results demonstrated the effectiveness of TGA as a tool able to address synthesis of coated CNTs to be employed as efficient drug delivery vectors in biomedical applications.

Modeling Solid State Stability for Speciation: A Ten-Year Long Study.

Speciation studies are based on fundamental models that relate the properties of biomimetic coordination compounds to the stability of the complexes. In addition to the classic approach based on solution studies, solid state properties have been recently proposed as supporting tools to understand the bioavailability of the involved metal. A ten-year long systematic study of several different complexes of imidazole substituted ligands with transition metal ions led our group to the definition of a model based on experimental evidences. This model revealed to be a useful tool to predict the stability of such coordination complexes and is based on the induced behavior under thermal stress. Several different solid state complexes were characterized by Thermally Induced Evolved Gas Analysis by Mass Spectrometry (TI-EGA-MS). This hyphenated technique provides fundamental information to determine the solid state properties and to create a model that relates stability to coordination. In this research, the model resulting from our ten-year long systematic study of complexes of transition metal ions with imidazole substituted ligands is described. In view of a systematic addition of information, new complexes of Cu(II), Zn(II), or Cd(II) with 2-propyl-4,5-imidazoledicarboxylic acid were precipitated, characterized, and studied by means of Thermally Induced Evolved Gas Analysis performed by mass spectrometry (TI-EGA-MS). The hyphenated approach was applied to enrich the information related to thermally induced steps, to confirm the supposed decomposition mechanism, and to determine the thermal stability of the studied complexes. Results, again, allowed supporting the theory that only two main characteristic and common thermally induced decomposition behaviors join the imidazole substituted complexes studied by our group. These two behaviors could be considered as typical trends and the model allowed to predict coordination behavior and to provide speciation information.