Super-resolution atomic force microscopy for in situ imaging

Atomic force microscopy (AFM) is widely used to image surfaces and interfaces at the nanometer scale. Typically the spatial resolution of imaging solid-liquid interfaces is limited to nanometers because of the deformation of the sample by the AFM tip apex. We are combining noncontact imaging and atomic scale simulation to understand how the interaction forces between a few atoms on the tip apex and a few atoms on the surface determine the imaging contrast. The knowledge is being applied to enable reproducible subnanometer resolution imaging, which will open up new opportunities in probing a variety of surfaces, including self-assembled monolayer-based biosensors, microarrays, electrocatalysts, and supported lipid bilayers, at the atomic scale.

Interfacial molecular recognition of biosensors

Biosensors that are capable of label-free, and miniaturized detection of biomarkers in complex biofluids have the transformative potentials in medical diagnosis. However, despite intense efforts, it remains prohibitively difficult to engineer biosensors with the required sensitivity, selectivity and reproducibility. One of the root causes is that the recognition of biomarkers by probe molecules immobilized on the transducer materials remain poorly understood and controlled.  What has been particularly unclear is how the nanoscale lateral organization of probe and captured target molecules influences molecular recognition. We have developed high resolution, in situ atomic force microscopy to map closely spaced individual probes as well as discrete hybridization events on a functioning electrochemical DNA sensor.  The high resolution structural information is helping us to develop mechanistic understandings and predictive models of interfacial molecular recognition.  Working with NASA researchers, we are leveraging our knowledge to engineer biosensors with the performance needed for health monitoring on space flights or detection of biomarkers of extraterrestrial life. 

Precision nanoparticle assemblies

Once nanoparticles are organized into assemblies, new and interesting collective properties may emerge. A number of studies are utilizing these new properties such as energy transfer, plasmonic coupling, for chemical and biochemical sensing.  However, it remains difficult to form complex assemblies with precise control over the geometry and separation.  We are using self-assembled DNA nanostructures to template the formation of nanoparticle assemblies with designed geometry.  These assemblies are showing promising potential in sensitive and specific detection of chemical and biochemical analytes. 


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