Part per Trillion Label-Free Electronic Bioanalytical Detection

Magliulo, Maria; Mallardi, Antonia; Gristina, Roberto; Ridi, Francesca; Sabbatini, Luigia; Cioffi, Nicola; Palazzo, Gerardo; Torsi, Luisa

doi:10.1021/ac302702n

Cited by 58 publications

(78 citation statements)

References 43 publications

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“…Root Mean Square Deviations (RMSDs) and Root Mean Square Fluctuations (RMSFs) were obtained after alignment of the trajectory to all the C-alpha atoms belonging to the monomer under investigation66676869707172737475…”

Section: Methodsmentioning

confidence: 99%

Organic bioelectronics probing conformational changes in surface confined proteins

Macchia

Alberga

Manoli

et al. 2016

Sci Rep

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The study of proteins confined on a surface has attracted a great deal of attention due to its relevance in the development of bio-systems for laboratory and clinical settings. In this respect, organic bio-electronic platforms can be used as tools to achieve a deeper understanding of the processes involving protein interfaces. In this work, biotin-binding proteins have been integrated in two different organic thin-film transistor (TFT) configurations to separately address the changes occurring in the protein-ligand complex morphology and dipole moment. This has been achieved by decoupling the output current change upon binding, taken as the transducing signal, into its component figures of merit. In particular, the threshold voltage is related to the protein dipole moment, while the field-effect mobility is associated with conformational changes occurring in the proteins of the layer when ligand binding occurs. Molecular Dynamics simulations on the whole avidin tetramer in presence and absence of ligands were carried out, to evaluate how the tight interactions with the ligand affect the protein dipole moment and the conformation of the loops surrounding the binding pocket. These simulations allow assembling a rather complete picture of the studied interaction processes and support the interpretation of the experimental results.

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Section: Methodsmentioning

confidence: 99%

Organic bioelectronics probing conformational changes in surface confined proteins

Macchia

Alberga

Manoli

et al. 2016

Sci Rep

Self Cite

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“…1) are two of the most studied semiconductor polymers having a wide range of applications ranging from organic thin-film transistors (OTFTs), solar cells, light emitting diodes to biosensors. [1][2][3][4][5][6] In particular, they are successfully used as the organic semiconductor layer (OSL) in the OTFTs. The performances of OTFTs are typically evaluated in terms of the mobility of charge carriers and are strongly affected by the morphology and the molecular order of the OSL.…”

Section: Introductionmentioning

confidence: 99%

Morphological and charge transport properties of amorphous and crystalline P3HT and PBTTT: insights from theory

Alberga

Perrier

Ciofini

et al. 2015

Phys. Chem. Chem. Phys.

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We explore the relation between the morphological and the charge transport properties of poly(3-hexylthiophene) (P3HT) and poly(2,5-bis(3-alkylthiophen-2-yl)thieno[3,2-b]thiophene) (PBTTT) semiconductor polymers in both amorphous and crystalline phases. Using molecular dynamics to simulate bulk supercells and the Marcus theory to analyze the transport properties we found that amorphous systems display a reduced hole mobility due to the loss of nematic order and π-π stacking leading to a reduction in the electronic coupling between two chains. In the crystal phase, PBTTT displays a larger charge mobility than P3HT due to the interdigitation of the side chains enhancing the stability of the conjugated rings on the backbones. This more stable π-π stacking reduces the energetic disorder with respect to P3HT and increases the electronic coupling. In contrast, in the amorphous phase, PBTTT displays a reduced charge mobility with respect to P3HT due to the absence of side chains attached to the thienothiophenes, which increases their fluctuations and the energetic disorder. In addition, we show that it is possible to calculate the reorganization energy neglecting the side chains of the polymers and thus saving computational time. Within this approximation, we obtained mobility values matching the experimental measurements, thus confirming that the side chains are crucial to shape the morphology of the polymeric systems but are not involved in the charge transport process.

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“…Moreover, electrochemical biosensors are compatible with microfluidics technologies, allowing for facile integration with microfluidic organs-on-a-chip platforms for continual monitoring of (multiple) secreted biomolecules in a noninvasive manner while consuming only small volumes of media. 17,18 …”

mentioning

confidence: 99%

Aptamer-Based Microfluidic Electrochemical Biosensor for Monitoring Cell-Secreted Trace Cardiac Biomarkers

et al. 2016

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Continual monitoring of secreted biomarkers from organ-on-a-chip models is desired to understand their responses to drug exposure in a noninvasive manner. To achieve this goal, analytical methods capable of monitoring trace amounts of secreted biomarkers are of particular interest. However, a majority of existing biosensing techniques suffer from limited sensitivity, selectivity, stability, and require large working volumes, especially when cell culture medium is involved, which usually contains a plethora of nonspecific binding proteins and interfering compounds. Hence, novel analytical platforms are needed to provide noninvasive, accurate information on the status of organoids at low working volumes. Here, we report a novel microfluidic aptamer-based electrochemical biosensing platform for monitoring damage to cardiac organoids. The system is scalable, low-cost, and compatible with microfluidic platforms easing its integration with microfluidic bioreactors. To create the creatine kinase (CK)-MB biosensor, the microelectrode was functionalized with aptamers that are specific to CK-MB biomarker secreted from a damaged cardiac tissue. Compared to antibody-based sensors, the proposed aptamer-based system was highly sensitive, selective, and stable. The performance of the sensors was assessed using a heart-on-a-chip system constructed from human embryonic stem cell-derived cardiomyocytes following exposure to a cardiotoxic drug, doxorubicin. The aptamer-based biosensor was capable of measuring trace amounts of CK-MB secreted by the cardiac organoids upon drug treatments in a dose-dependent manner, which was in agreement with the beating behavior and cell viability analyses. We believe that, our microfluidic electrochemical biosensor using aptamer-based capture mechanism will find widespread applications in integration with organ-on-a-chip platforms for in situ detection of biomarkers at low abundance and high sensitivity.

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Part per Trillion Label-Free Electronic Bioanalytical Detection

Cited by 58 publications

References 43 publications

Organic bioelectronics probing conformational changes in surface confined proteins

Organic bioelectronics probing conformational changes in surface confined proteins

Morphological and charge transport properties of amorphous and crystalline P3HT and PBTTT: insights from theory

Aptamer-Based Microfluidic Electrochemical Biosensor for Monitoring Cell-Secreted Trace Cardiac Biomarkers

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