Selected Publications All Publications

Biomolecular electrochemical sensors

Our research group was one of the first to use nanostructured materials to develop high-sensitivity electrochemical sensors for biomolecular analytes.  Over the last ten years, we have applied these sensors to a range of biological targets relevant to the diagnosis of cancer and infectious disease, and have applied them in other areas related to transplant and regenerative medicine.

Das, J.; Ivanov, I.; Safaei, T. S.; Sargent, E. H.; Kelley, S. O. Combinatorial Probes for High-Throughput Electrochemical Analysis of Circulating Nucleic Acids in Clinical Samples.
Angew. Chem. Intl. Ed. 2018, 57 (14), 3711–3716. https://doi.org/10.1002/anie.201800455.

De Luna, P.; Mahshid, S. S.; Das, J.; Luan, B.; Sargent, E. H.; Kelley, S. O.; Zhou, R. High-Curvature Nanostructuring Enhances Probe Display for Biomolecular Detection.
Nano Lett. 2017, 17 (2), 1289–1295. https://doi.org/10.1021/acs.nanolett.6b05153.

Das, J.; Ivanov, I.; Sargent, E. H.; Kelley, S. O. DNA Clutch Probes for Circulating Tumor DNA Analysis.
J. Am. Chem. Soc. 2016, 138 (34), 11009–11016. https://doi.org/10.1021/jacs.6b05679.

Das, J.; Ivanov, I.; Montermini, L.; Rak, J.; Sargent, E. H.; Kelley, S. O. An Electrochemical Clamp Assay for Direct, Rapid Analysis of Circulating Nucleic Acids in Serum.
Nature Chemistry 2015, 7 (7), 569–575. https://doi.org/10.1038/nchem.2270.

Sage, A. T.; Besant, J. D.; Mahmoudian, L.; Poudineh, M.; Bai, X.; Zamel, R.; Hsin, M.; Sargent, E. H.; Cypel, M.; Liu, M.; et al. Fractal Circuit Sensors Enable Rapid Quantification of Biomarkers for Donor Lung Assessment for Transplantation.
Science Adv. 2015, 1 (7), e1500417.https://doi.org/10.1126/sciadv.1500417.

Das, J.; Cederquist, K. B.; Zaragoza, A. A.; Lee, P. E.; Sargent, E. H.; Kelley, S. O. An Ultrasensitive Universal Detector Based on Neutralizer Displacement.
Nature Chemistry 2012, 4 (8), 642–648. https://doi.org/10.1038/nchem.1367.

Soleymani, L.; Fang, Z.; Lam, B.; Bin, X.; Vasilyeva, E.; Ross, A. J.; Sargent, E. H.; Kelley, S. O. Hierarchical Nanotextured Microelectrodes Overcome the Molecular Transport Barrier to Achieve Rapid, Direct Bacterial Detection. ACS Nano 2011, 5 (4), 3360–3366. https://doi.org/10.1021/nn200586s.

Vasilyeva, E.; Lam, B.; Fang, Z.; Minden, M. D.; Sargent, E. H.; Kelley, S. O. Direct Genetic Analysis of Ten Cancer Cells: Tuning Sensor Structure and Molecular Probe Design for Efficient MRNA Capture.
Angew. Chem. Intl. Ed. 2011, 50 (18), 4137–4141. https://doi.org/10.1002/anie.201006793.

Soleymani, L.; Fang, Z.; Sargent, E. H.; Kelley, S. O. Programming the Detection Limits of Biosensors through Controlled Nanostructuring.
Nature Nanotechnol. 2009, 4 (12), 844–848. https://doi.org/10.1038/nnano.2009.276.

Soleymani, L.; Fang, Z.; Sun, X.; Yang, H.; Taft, B. J.; Sargent, E. H.; Kelley, S. O. Nanostructuring of Patterned Microelectrodes to Enhance the Sensitivity of Electrochemical Nucleic Acids Detection.
Angew. Chem. Intl. Ed. 2009, 48 (45), 8457–8460. https://doi.org/10.1002/anie.200902439.

Yang, H.; Hui, A.; Pampalakis, G.; Soleymani, L.; Liu, F. F.; Sargent, E. H.; Kelley, S. O. Direct, Electronic MicroRNA Detection for the Rapid Determination of Differential Expression Profiles.
Angew. Chem. Intl. Ed. 2009, 48 (45), 8461–8464. https://doi.org/10.1002/anie.200902577.

Rare / single cell profiling

Our laboratory has developed a new cellular profiling technology – magnetic ranking cytometry – that is a powerful tool for the analysis of rare cells. By labeling cells with magnetic nanoparticles and using microfluidic devices to evaluate the level of magnetic labeling, we can collect information concerning protein and RNA analysis at the single cell level. We have applied this technology to analyzing circulating tumor cells and rare stem cells and have also used this approach to create new tools for high-throughput functional genomics.

Aldridge, P. M.; Mukhopadhyay, M.; Ahmed, S. U.; Zhou, W.; Christinck, E.; Makonnen, R.; Sargent, E. H.; Kelley, S. O. Prismatic Deflection of Live Tumor Cells and Cell Clusters.
ACS Nano 2018, 12 (12), 12692–12700. https://doi.org/10.1021/acsnano.8b07616.

Labib, M.; Mohamadi, R. M.; Poudineh, M.; Ahmed, S. U.; Ivanov, I.; Huang, C.-L.; Moosavi, M.; Sargent, E. H.; Kelley, S. O. Single-Cell MRNA Cytometry via Sequence-Specific Nanoparticle Clustering and Trapping.
Nature Chemistry 2018, 10 (5), 489. https://doi.org/10.1038/s41557-018-0025-8.

Poudineh, M.; Aldridge, P. M.; Ahmed, S.; Green, B. J.; Kermanshah, L.; Nguyen, V.; Tu, C.; Mohamadi, R. M.; Nam, R. K.; Hansen, A.; et al. Tracking the Dynamics of Circulating Tumour Cell Phenotypes Using Nanoparticle-Mediated Magnetic Ranking.
Nat. Nanotechnology 2017, 12 (3), 274–281. https://doi.org/10.1038/nnano.2016.239.

Labib, M.; Green, B.; Mohamadi, R. M.; Mepham, A.; Ahmed, S. U.; Mahmoudian, L.; Chang, I. H.; Sargent, E. H.; Kelley, S. O. Aptamer and Antisense-Mediated Two-Dimensional Isolation of Specific Cancer Cell Subpopulations. 
J. Am. Chem. Soc.2016https://doi.org/10.1021/jacs.5b10939.

Mohamadi, R. M.; Besant, J. D.; Mepham, A.; Green, B.; Mahmoudian, L.; Gibbs, T.; Ivanov, I.; Malvea, A.; Stojcic, J.; Allan, A. L.; et al. Nanoparticle-Mediated Binning and Profiling of Heterogeneous Circulating Tumor Cell Subpopulations. Angew. Chem. Intl. Ed. 2015, 54 (1), 139–143. https://doi.org/10.1002/anie.201409376.

Intracellular probes

We have developed a family of probes that exhibit strong subcellular localization profiles and we have used these compounds to explore site-specific chemistry within the cell.  We have applied these probes to the study of new mitochondrial biology and are using them as the basis for high-throughput screens of new mitochondrial function.

Lei, E. K.; Kelley, S. O. Delivery and Release of Small-Molecule Probes in Mitochondria Using Traceless Linkers.
J. Am. Chem. Soc. 2017, 139 (28), 9455–9458. https://doi.org/10.1021/jacs.7b04415.

Wisnovsky, S.; Jean, S. R.; Kelley, S. O. Mitochondrial DNA Repair and Replication Proteins Revealed by Targeted Chemical Probes.
Nature Chemical Biology 2016, 12 (7), 567–573. https://doi.org/10.1038/nchembio.2102.

Wisnovsky, S. P.; Wilson, J. J.; Radford, R. J.; Pereira, M. P.; Chan, M. R.; Laposa, R. R.; Lippard, S. J.; Kelley, S. O. Targeting Mitochondrial DNA with a Platinum-Based Anticancer Agent.
Chem. Biol. 2013, 20 (11), 1323–1328. https://doi.org/10.1016/j.chembiol.2013.08.010.

Chamberlain, G. R.; Tulumello, D. V.; Kelley, S. O. Targeted Delivery of Doxorubicin to Mitochondria.
ACS Chem. Biol. 2013, 8 (7), 1389–1395. https://doi.org/10.1021/cb400095v.

Pereira, M. P.; Kelley, S. O. Maximizing the Therapeutic Window of an Antimicrobial Drug by Imparting Mitochondrial Sequestration in Human Cells.
J. Am. Chem. Soc. 2011, 133 (10), 3260–3263. https://doi.org/10.1021/ja110246u.

Fonseca, S. B.; Pereira, M. P.; Mourtada, R.; Gronda, M.; Horton, K. L.; Hurren, R.; Minden, M. D.; Schimmer, A. D.; Kelley, S. O. Rerouting Chlorambucil to Mitochondria Combats Drug Deactivation and Resistance in Cancer Cells. Chem. Biol. 2011, 18 (4), 445–453.https://doi.org/10.1016/j.chembiol.2011.02.010.

Horton, K. L.; Stewart, K. M.; Fonseca, S. B.; Guo, Q.; Kelley, S. O. Mitochondria-Penetrating Peptides.
Chem. Biol. 2008, 15 (4), 375–382. https://doi.org/10.1016/j.chembiol.2008.03.015.

DNA-templated materials

DNA sequences can be used to program the properties of nanomaterials and also facilitate their self-assembly. Our research group developed the first DNA-programmed method allowing the systematic synthesis and functionalization of semiconductor quantum dots.  These materials have been used to develop agents for drug delivery and intracellular sensing.

Zhang, L.; Jean, S. R.; Li, X.; Sack, T.; Wang, Z.; Ahmed, S.; Chan, G.; Das, J.; Zaragoza, A.; Sargent, E. H.; et al. Programmable Metal/Semiconductor Nanostructures for MRNA-Modulated Molecular Delivery.
Nano Lett. 2018, 18 (10), 6222–6228. https://doi.org/10.1021/acs.nanolett.8b02263.

Zhang, L.; Jean, S. R.; Ahmed, S.; Aldridge, P. M.; Li, X.; Fan, F.; Sargent, E. H.; Kelley, S. O. Multifunctional Quantum Dot DNA Hydrogels.
Nature Commun. 2017, 8 (1), 381. https://doi.org/10.1038/s41467-017-00298-w.

Tikhomirov, G.; Hoogland, S.; Lee, P. E.; Fischer, A.; Sargent, E. H.; Kelley, S. O. DNA-Based Programming of Quantum Dot Valency, Self-Assembly and Luminescence.
Nature Nanotechnol. 2011, 6 (8), 485–490. https://doi.org/10.1038/nnano.2011.100.

Ma, N.; Sargent, E. H.; Kelley, S. O. One-Step DNA-Programmed Growth of Luminescent and Biofunctionalized Nanocrystals.
Nature Nanotechnol. 2009, 4 (2), 121–125. https://doi.org/10.1038/nnano.2008.373.

Electrocatalysis with nanostructured materials

As part of a collaborative team, we work on developing new approaches for the synthesis of renewable fuels.  Our approach typically relies on nanostructured materials that can be used for electrocatalytic synthesis.

De Luna, P.; Quintero-Bermudez, R.; DInh, C. T.; Ross, M. B.; Bushuyev, O. S.; Todorović, P.; Regier, T.; Kelley, S. O.; Yang, P.; Sargent, E. H. Catalyst Electro-Redeposition Controls Morphology and Oxidation State for Selective Carbon Dioxide Reduction.
Nature Catal. 2018, 1 (2), 103–110. https://doi.org/10.1038/s41929-017-0018-9.

Liu, M.; Pang, Y.; Zhang, B.; De Luna, P.; Voznyy, O.; Xu, J.; Zheng, X.; Dinh, C. T.; Fan, F.; Cao, C.; et al. Enhanced Electrocatalytic CO2 Reduction via Field-Induced Reagent Concentration.
Nature 2016, 537 (7620), 382–386. https://doi.org/10.1038/nature19060.

Saberi Safaei, T.; Mepham, A.; Zheng, X.; Pang, Y.; Dinh, C. T.; Liu, M.; Sinton, D.; Kelley, S. O.; Sargent, E. H. High-Density Nanosharp Microstructures Enable Efficient CO2 Electroreduction.
Nano Lett. 2016, 16 (11), 7224–7228. https://doi.org/10.1021/acs.nanolett.6b03615.

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