Nano and Pico Characterization Laboratory
Fundamental and applied research relies on the detection and characterization of physical observables related to matter, energy and time. To overcome the limitations imposed by any one individual technique, the NPC Team seeks to merge an extensive knowledge base in scanning probe microscopy with other physical methods of characterization to generate multidimensional datasets that serve to bridge resolution gaps and integrate structural information. In addition to pushing the limits of spatial resolution, real-time spatiotemporal measurements of dynamic processes are fast becoming a limiting capacity in modern sensing and computation, especially in cases where multi-input, distributed datasets are employed. Although integrated detection, measurement, and imaging systems are hard to come by; a motto of our group remains “if you can’t buy it, you build it”.
Cognitive Computing through Physical Intelligence: Neuromorphic Atomic Switch Networks
We have set out to examine the “pure” essence of intelligence as the ability of objects to learn the laws (correlations) of informative environments. Natural systems tend to be complex and dynamic, where the collective interactions between elements of the system serve to create emergent properties that cannot be described by simply extension from knowledge of the individual elements. While synthetic systems provide a unique opportunity to develop models of and methods for examination of complexity, the fabrication of micro- and nanoscale devices with complex architectures, especially those with some degree of random structural topology, is difficult using traditional methods. Combining directed and self-assembly of functional nanoscale building blocks into complex network architectures offers a promising route to creating intricate patterns of nanoscale components alongside the benefits of scalability and ease of fabrication. Self-assembled networks of non-linear elements have been recently presented as a unique implementation of a purpose-built electronic devices that provide a robust, flexible, and scalable experimental platform for controlled examinations of complexity, criticality and their potential toward implementing unconventional, biologically inspired computational paradigm in a synthetic experimental system.
Sponsored by WPI Center for Materials Nanoarchitectonics (MANA), National Institute of Materials Science (NIMS), Japan and the Defense Advanced Research Projects Agency (DARPA), US Defense Sciences Office (DSO).
Nanocytology Cancer Diagnostics
Cancer diagnosis traditionally relies on visual analysis or molecular biological techniques, such as immune-based assays and genomics. Advancement in diagnostic approaches aim to improve accuracy while decreasing the feedback time required to determine therapeutic efficacy. While tremendous progress has been made in recent decades, the application of new physical methods to biomedical research and clinical diagnostics remains a potentially rich field for fundamental scientific inquiry and subsequent translational efforts. Exploring the landscape for emerging technologies serves to provide complementary, orthogonal approaches to address long-standing challenges in clinical diagnostics and therapeutics.
It is now evident that biomechanics and the biophysical properties of cells are important for understanding cancer at the cellular level. Cell stiffness (Young’s modulus), as determined by nano-mechanical measurements using Atomic Force Microscopy (AFM) is a newly recognized cellular phenotype characteristic associated with cancer cells. This work focuses on translational activities enabling atomic force microscopy (AFM)-based technology development and application for cancer diagnosis. The project builds on the recent discovery of nanocytology as a predictive biomechanical marker for the progression and chemosensitivity of human cancer.
Biophysical Regulation of Stem Cell Development
A major hurdle for the cardiac stem cell therapy is the fact that embryonic stem cells, even after differentiation into cardiomyocytes with various genetic approaches, remains phenotypically at the fetal stages in culture. Critical for the application of PSCs to the cardiac regeneration is a comprehensive understanding of the role of biophysical environment during their maturation. We hypothesize that bio-electromechanical cues are required for further maturation of the stem cell derived cardiomyocytes. We have established a foundation for multifaceted solutions to various technical hurdles: selection of the optimal human embryonic stem cell (hESC) lines, optimization of the readout of the functional/genetic/epigenetic maturation of hESC-derived cardiomyocytes using cellular force spectroscopy (CFS) and live cell mechanical imaging interferometry (MII) unique to our labs, structural characterization via super-resolution confocal microscopy (STED), and feedback-controlled application of the electro-mechanical forces to the embryoid bodies by customized multielectrode arrays (MEA). Success will elucidate a fundamental principle of cardiac maturation and unlock the maturation block of PSC-derived cardiomyocytes, a critical barrier between current cardiac stem cell research and future regenerative medicine.
Chemistry, physics and mechanics of biomolecules
To understand biological processes at the molecular level it is essential to identify the involved proteins and their assemblies, to characterize their structure and function, and to unravel their interplay with other proteins and molecules. Techniques like X-ray crystallography, electron microscopy and nuclear magnetic resonance spectroscopy have contributed greatly to elucidate the structure and properties of biomolecular complexes. A fundamental aspect of such bionanostructures, such as cytoskeletal F-actin filaments, is the ability to reorganize their spatial structure and nanoscale mechanics. AFM offers a unique capability for direct 3D imaging of single actin filaments without electron dense staining, fixation, or extreme temperatures with imaging resolution comparable to that of electron microscopes. Additionally, AFM is a versatile technique that also brings information on structures, mechanics, dynamics and specific bio-molecular binding interactions under physiological solvent conditions. This research has the long term goal of programmed interrogation and functionality of single molecules using AFM.