A key element of the study was being able to measure binding affinities of the peptide to dPKC. Using Agile, the researchers were able to show that different peptides were binding to different regions of dPKC, thus explaining the different biological effects of the tested peptides. The end result is a highly specific, highly potent peptide inhibitor for protein-protein interactions between dPKC and substrate proteins as well as demonstration of an exciting, generalizable approach for creation of peptide therapeutics.
Publications Referencing Agile
Digital Biosensing by Foundry-Fabricated Graphene Sensors
Scientific Reports by Nature Research
Techniques such as Field Effect Biosensing are capable of rapid and flexible biological testing. Until now, access to this new technology has been limited to academic researchers focused on bioelectronic devices and their collaborators. Here we show that this capability is retained in an industrially manufactured device, opening access to this technology generally. Access to this type of production opens the door for rapid deployment of nanoelectronic sensors outside the research space. The low power and resource usage of these biosensors enables biotech engineers to gain immediate control over precise biological and environmental data.
Graphene-based Biosensor for On-chip Detection of Bio-orthogonally Labeled Proteins to Identify the Circulating Biomarkers of Aging
Lab on a Chip
In this publication, the Keck Graduate Institute (KGI) at Claremont Colleges uses the Agile graphene biosensor to develop a lab-on-a-chip with reduced sample size, complexity, cost, and time as compared to optical assays and mass spectrometry.
Synthetic Molecules for Disruption of the MYC Protein-Protein Interface
Bioorganic & Medicinal Chemistry
In this paper, the authors found that Agile successfully characterized MYC better than surface plasmon resonance (SPR) due to 1) A much lower limit of detection as compared with SPR or isothermal calorimetry (ITC), 2) Agile’s graphene surface which reduces non-specific binding with MYC as compared to a dextran surface, 3) The ability to avoid aggregation of target during immobilization due to the low concentration binding surface of the Agile biosensor.
Novel Graphene-based Biosensor for Early Detection of Zika Virus Infection
Biosensors and Bioelectronics
The compact and portable Agile uses an immobilized monoclonal antibody developed by the Centers for Disease Control and Prevention (CDC) to detect Zika virus antigen in serum. The LLOD and specificity demonstrated provide an opportunity for early stage detection.
FEB Increases Signal-to-Noise by 10 Times versus BLI and ELISA
Agile, a Field Effect Biosensing (FEB) system, detected Zika viral antigen at a concentration 10 times lower than on a BLI system in this breakthrough study. The platform also lowered the limit of detection by 10 times versus an ELISA for inflammatory protein IL-6.
Correcting Mitochondrial Fusion By Manipulating Mitofusin Conformations
In this joint publication by researchers from the Washington University School of Medicine, Albert Einstein College of Medicine, and Stanford University School of Medicine, Agile provided sensitive in vitro kinetic binding data that supports the model of positive cooperativity of two therapeutic minipeptides engineered by the researchers.
Engineered Substrate-Specific Delta PKC Antagonists to Enhance Cardiac Therapeutics
Delta protein kinase C (dPKC) is an enzyme involved with many signal transduction pathways, playing an important role in cancer, neurodegenerative diseases, and heart disease. Nir Qvit leads a study seeking to create a peptide based drug to prevent heart damage related to dPKC. To do this, they have performed a structure-activity-relationship study with a set of designed peptides. The peptides were tested for binding affinity using the Agile system, and were tested for efficacy in cell culture and animal tissue. The researchers show significant protection of cardiac tissue using their rationally designed peptides.
Large Scale Commercial Fabrication of High Quality Graphene-Based Assays for Biomolecule Detection
Sensors & Actuators: B. Chemical
Enzyme-protein and antibody-antigen binding experiments performed with Agile shown in this peer-reviewed paper demonstrate sensitivity down to pM levels, detection in complex media such as serum, and alignment with published equilibrium dissociation constants.
Selective Phosphorylation Inhibitor of Delta Protein Kinase C–Pyruvate Dehydrogenase Kinase Protein–Protein Interactions: Application for Myocardial Injury in Vivo
Journal of the American Chemical Society
This paper describes the use of Agile to gain in vitro kinetic binding measurements between a peptide inhibitor and a kinase enzyme for the treatment of chronic heart disease. The measurements had not been able to be attained using traditional methods due to the instability of the protein kinase.
Publications About Graphene Biosensors
Versatile Graphene Biosensors for Enhancing Human Cell Therapy
Biosensors and Bioelectronics
Cell-based therapy requires extensive preclinical characterization of biomarkers indicating mechanisms of action crucial to the desired therapeutic effect, and the challenge to achieve high-quality measurement is increasingly met by progress in biosensor design. A commercially-available graphene field effect transistor (G-FET) biosensing chip, the Agile, has been reported to robustly measure clinically-relevant target molecules (peptides, proteins, antibodies) in real time for dynamic pM level characterization in complex media.
ZIKA: A New System to Empower Health Workers and Local Communities to Improve Surveillance Protocols by E-learning and to Forecast Zika
Digital Health Conference
The devastating consequences of neonates infected with the Zika virus makes it necessary to fight and stop the spread of this virus. An essential part of the fight is the use of mobile technology to support routine surveillance by health workers. A cost-effective and portable graphene-enabled biosensor such as Agile is proposed to improve the turnaround time in confirming ZIKV cases.
Graphene as Biomedical Sensing Element: State of Art Review and Potential Engineering Applications
Composites Part B: Engineering
There has been abundant interest in using graphene material in biomedical sensor devices due to excellent biocompatibility, conductivity, cell growing properties, and surface behavior. This article reviews the use of graphene in miniaturized and biomedical sensors, and Agile is noted as a cost-effective graphene biosensor for Zika virus detection.
Three-Dimensional Nanostructured Graphene: Synthesis and Energy, Environmental and Biomedical Applications
This review article covers areas in which graphene has been exploited for biomedical applications. Agile is referenced as a potential graphene biosensor for diagnostics.
Switch-On the LAMP to Spot Zika
Annals of Translational Medicine
Zika has been called a public health emergency of international concern. This paper describes detection of Zika virus by loop-mediated isothermal amplification (LAMP) of viral RNA. Additionally, it calls out NS1 antigen-capture point-of-care platforms such as Agile as an alternative to nucleic-acid detection.
Scalable Graphene Aptasensors for Drug Quantification
Simpler and more rapid approaches for therapeutic drug-level monitoring are highly desirable to enable use at point-of-care. This paper describes a scalable approach for fabrication of arrays of GFET-based aptasensors and demonstrated sensitive (∼1 nM) and specific detection of the target tenofovir, with a process based on CVD-grown graphene and photolithographic processing, making it suitable for scale-up to industrial production. Nanomedical Diagnostics is referenced as the mass-manufacturer of GFET-based sensors.