Health and Biological Systems

Photonics and nanoelectronics, together with quantitative modeling and analysis, naturally apply to the interfacing with biological systems, as investigative tools, or as sensors of electric or chemical activity. Research efforts in this areas contribute from outside a direct health care setting to the improvement of the knowledge and tools that promote health. Below some examples of current activities related to photonics and electronics, from faculty from different departments and different colleges. They go from the development of new materials and devices, to the fundamental investigation sof biological processes.

Conjugated polymers and organic electronics

In the Chemical and Biomolecular Engineering department, Elsa Reichmanis‘ lab investigates the chemistry and properties of polymeric and nanostructured materials for advanced optoelectronics via the design and development of organic or organic/hybrid semiconductor systems for flexible and stretchable electronics (such as transistors), and the control of polymer/hybrid semiconductor organization at the molecular through meso-scales. Incorporation of such technologies on organic flexible substrates will lead to new types of biological sensors.

The group also works on mixed ionic-electronic organic conductors. These materials promise to serve as central building blocks for a myriad of applications, including battery electrodes, supercapacitors, electrochromic devices, actuators, and organic bioelectronics. In the latter domain, they offer opportunities to be used as active materials for low voltage, bio-electrochemical devices, such as organic electronic ion pumps, neuromorphic modules, electrophysiological monitoring, and organic electrochemical transistors. As such, these materials are emerging as a mainstay contemporary sensing platform, and the group is focused on investigating materials for future designs.

Optical biosensors

Prof. Himanshu Jain in the department of Materials Science and Engineering, a specialist on glasses, has demonstrated a proof-of-concept of evanescent wave mid-infrared biosensors for the qualitative and quantitative analysis of various chemical and biological species, and is interested in its practical development. Waveguides and fiber-optic materials transparent in the mid-IR spectral region offer access to fundamental vibrational fingerprint absorptions of organic molecules. These sensors are label-free, unlike the majority of array-based assays that currently employ fluorescent, enzymatic, or radiolabeled biomolecules for target recognition.

Mid-infrared sensing and some other modalities of biosensing such as surface enhanced Raman spectroscopy rely on the availability of appropriate metal nanoparticles in a transparent substrate such as a glass slide. The Jain group is also developing techniques for the fabrication of such nanocomposites with prescribed spatial and size distribution of nanoparticles.

THz semiconductor lasers and detectors

Prof. Sushil Kumar’s group in the department of electrical and computer engineering is working semiconductor lasers and detectors that operate in a wide wavelength range between 60 and 150 micrometers (frequencies between 2 and 5 THz). These THz laser are of interest for several chemical and biomolecular sensing schemes that find applications in spectroscopy of drugs in pharmaceutical industry as well as in industrial applications in general, because of unique spectral fingerprints that chemicals show in the terahertz region of the electromagnetic spectrum.

Optogenetics

Also in the department of electrical and computer engineering, Prof. Ning Li specializes on several types of devices that can be applied to optogenetics, the biological technique to control the activity of neurons or other cell types with light. This is achieved by expression of light-sensitive ion channels, pumps or enzymes specifically in the target cells. In systems neuroscience, the ability to control the activity of a genetically defined set of neurons has been used to understand their contribution to decision making, learning, fear memory, mating, addiction, feeding, and locomotion. The sensor typically involves semiconductor-based light-emitting diodes (LEDs), typically in the form of micro-LED light sources and sensitive photodetectors integrated on sharp tips that are either placed close to the brain tissue or inside the brain tissue. The group has experience on such devices and fabrication processes, demonstrating novel very efficient LEDs that produce much less heat than previously demonstrated. This is crucial, as the tissue temperature increase of one or two degrees will cause severe side effects.

In vitro neural circuits

In Electrical and Computer Engineering and Bioengineering, Prof. Yevgeny Bardichevsky’s Neural Engineering Lab uses large area multiple-electrodode arrays and microfluidics for high throughput drug screening and development, brain slice cultures, and polymer microfluidic devices to study how axons sprout and neural circuits develop. Working on In vitro models of neural circuits, the group seeks to reproduce, in a dish, circuit-level information processing that can be disrupted by psychiatric and neurological disorders. Transferring computational paradigms into living neural networks, the group develped an optical neuromodulation technique that made it possible to avoid or suppress chaotic circuit activity, and found that circuits composed of living neurons are capable of precise conversion of temporal patterns of neural activity into spatial ones. The group also developed a microfabrication-based method to ensure directionality of neuronal connectivity between 3D neuronal networks. These activities are already leading to new discoveries about the effect of physical constraints on epileptiform bursts in neuronal networks in vitro, which may lead to new insights into the development of epilepsy after brain trauma.

Lipid membranes, a key biological system

Lipid membranes and membrane-associated proteins, and their physical properties related t their structure, dynamics, and fluid flow are of interest to the biophysical community because they have the potential to affect the function of cell membranes. In the department of Physics, Prof. Honerkamp-Smith’s group uses microscopy and neutron reflectometry to probe micro- and nanoscale flow responses in lipid bilayers. They can also apply microfluidic shear flow to membranes, imposing femtonewton-scale forces to individual molecules in order to probe the mechanics of soft materials.  Many cells sense flow in order to regulate important physiological functions. Yet in many important cases, the mechanistic details of flow sensing are unknown. To meet this need, they developed new experimental methods to make quantitative measurements of mechanical forces on membrane proteins, using supported lipid bilayers as a simplified model system. Fundamental membrane mechanical properties govern important biological processes such as metabolism and infection resistance. Perpendicular to the membrane plane, lipid membranes interrupt fluid flow whereas parallel to the membrane, lipids circulate along with flow. When membranes are supported on solid substrates, circulation is prevented. Instead, parallel flow exerts shear stress on the membrane.

Micro-characterization of cellular mechanisms

Prof. Ou-Yang’s lab in the physics department uses advanced optical imaging and micro-characterization tools such as optical tweezing and “optical bottles” to study materials at the interface between living and nonliving systems. The group has expertise in colloids and the statistical physics of macromolecule diffusion, and studies how micro-rheological  properties of living cells are influenced by the chemical or mechanical environment surrounding them. They also look at how dynamic movements of the intracellular domain are affected by the physicochemical parameters of the extracellular matrix in which the cells are embedded. This research is based on experimental studies of the structure-dynamic relationships and the development of theoretical tools to model these behaviors.

Mathematical and computational models of cellular biophysics

In the physics department, the theoretical research group of Prof. Vavylonis works in cellular biophysics to gain insights into the physical principles governing the function and organization of living cells. In this way the group develops a new understanding of the intricacies with which a cell can organize its contents or change its shape by complex self-assembly and self-disassembly of the internal structures that build its skeleton. The primary interest lies in the cytoskeleton, a crucial component of cells that forms various structures responsible for mechanical integrity, shape maintenance, and motor-driven movement. Through collaborations with biologists and biophysicists, the group applies techniques from statistical physics, soft matter physics, and nonlinear dynamics to investigate specific biological processes. These processes include the functioning of the actomyosin contractile ring during cell division (cytokinesis) and cell polarization for tasks such as cell motion, mating, and growth. Actin filaments, in particular, exhibit a wide array of structures at the micrometer scale, including branched networks, cortical networks, contractile stress fibers, and parallel bundles. These structures serve various functions that cells can dynamically adjust, relying on fundamental mechanisms such as actin filament nucleation, cross-linking, motor-driven transport, severing, and depolymerization. These processes involve intricate interactions between the cytoskeleton and cell membranes and have wide-ranging implications, from developmental biology to cancer cell metastasis.

The research carried out by the Vavylonis group contributes to a deeper comprehension of cellular dynamics with potential implications for health and material science applications. For example, understanding the biochemical and biophysical mechanisms that govern cytoskeletal organization motivates the development of biomimetic self-organizing materials. This knowledge holds the potential to inform the design of advanced materials for applications in optics, nanophotonics, and self-assembled meta-materials