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Neuro- or Biohybrid systems to synthesize fuels, and chemicals and act as sensors for military

Neuro- or Biohybrid systems are systems formed by at least one biological component – i.e. already existing in living systems – and at least one artificial – newly engineered – component. Biological and artificial components are not independent but are passing information either in one or both directions, thereby forming a new hybrid bio-artificial entity.


One implementation of bio–hybrid system consists of a passive and a biological active layer working in parallel. When an external electrical stimulus activates the myocytes in the biological layer, the cells contract; the global effect of the contraction may be either the stretching or the bending of the specimen.


Important implementation examples of biohybrid systems are brain-machine interfaces, where neurons and their molecular machineries are connected to microscopic sensors and actuators by means of electrical or chemical communication, either in vitro or in the living organism. Neurotechnology address basic understanding of biophysical properties of neuron-chip interfacing, technological aspects and constrains in fabricating biohybrid devices, and provide cues on their in-vitro and in-vivo applications in brain research.


Understanding biological systems presents unique opportunities for developing new defense capabilities through mimicry, integration of living and non-living components, or direct use of complex biological systems, says DARPA. Biohybrid systems implies the direct use of biological components like developing insect antennae to hand held device to detect odorant plume.


Biological signaling processes in intelligent materials

Scientists from the University of Freiburg have developed materials systems that are composed of biological components and polymer materials and are capable of perceiving and processing information. These biohybrid systems were engineered to perform certain functions, such as the counting signal pulses in order to release bioactive molecules or drugs at the correct time, or to detect enzymes and small molecules such as antibiotics in milk. The interdisciplinary team presented their results in some of the leading journals in the field, including Advanced Materials and Materials Today.


Living systems (such as cells and organisms) and electrical systems (such as computers) respond to different input information and have diverse output capabilities. However, the fundamental property these complex systems share is the ability to process information. Over the past two decades, scientists have applied the principles of electrical engineering to design and build living cells that perceive and process information and perform desired functions. This field is called synthetic biology, and it has many exciting applications in the medical, biotechnology, energy and environmental sectors.


“Thanks to major progress in our understanding of the components and wiring of biological signalling processes, we are now at a stage where we can transfer biological modules from synthetic biology to materials,” explains lead researcher Prof. Wilfried Weber from the Faculty of Biology and the BIOSS Centre for Biological Signalling Studies. A critical step in the development of these smart materials systems was to optimally align the activity of the biological building blocks. Similar to computers, incompatibility of individual components might crash the overall system. Key to overcoming this challenge were quantitative mathematical models developed by Prof. Jens Timmer and Dr. Raphael Engesser from the Faculty of Mathematics and Physics.


“A great thing about these synthetic biology-inspired materials systems is their versatility,” says Hanna Wagner, the first author of one of the studies and a doctoral candidate in the Spemann Graduate School of Biology and Medicine (SGBM). The modular design concept put forth in these studies provides a blueprint for engineering biohybrid materials systems that can sense and process diverse physical, chemical or biological signals and perform desired functions, such as the amplification of signals, the storage of information, or the controlled release of bioactive molecules. These innovative materials might therefore have broad applications in research, biotechnology and medicine.



Scaling up biohybrid systems to synthesize fuels, chemicals

Bioelectrochemical systems combine the best of both worlds – microbial cells with inorganic materials – to make fuels and other energy-rich chemicals with unrivaled efficiency. Yet technical difficulties have kept them impractical anywhere but in a lab. Now researchers at Lawrence Berkeley National Laboratory (Berkeley Lab) have developed a novel nanoscale membrane that could address these issues and pave the way for commercial scale-up.


The nanoscale membrane is embedded with molecular wires that simultaneously chemically separate, yet electrochemically couple, a microbial and an inorganic catalyst on the shortest possible length scale. This new modular architecture, described in a paper published recently in Nature Communications, opens up a large design space for building scalable biohybrid electrochemical systems for a variety of applications, including electricity generation, waste remediation, and resource recovery, in addition to chemical synthesis.


The work was led by Heinz Frei, a senior scientist in Berkeley Lab’s Molecular Biophysics and Integrated Bioimaging Division (MBIB), and Caroline Ajo-Franklin, a staff scientist with Berkeley Lab’s Molecular Foundry who holds a secondary appointment in MBIB.


“This advance introduces a completely new architecture for bioelectrochemical systems based on nanoscale integration and provides a path forward to scaling up these systems to a commercially relevant level,” said Frei. “What’s more, it provides an example of how a key design principle inspired by biology is applied for solving a major scientific gap of engineered systems.”


Biohybrid electrochemical systems employ separate microbial and inorganic catalysts in oxidation-reduction, or redox, reactions, to capitalize on the complementary strengths of each component. Microbes can synthesize complex molecules with high selectivity, while inorganic catalysts are the most efficient energy collectors. Such biohybrid systems are attractive as a sustainable technology to produce fuels and high-value chemicals using renewable energy.


But, a fundamental challenge in designing biohybrid systems is that the environments that support optimal function of living cells and inorganic materials are chemically incompatible, resulting in toxicity, corrosion, or efficiency-degrading cross reactions. To date, the approach has been to keep the biological and abiotic components physically separated by macroscopic (millimeter to centimeter) distances. However this exacts a high cost in terms of efficiency, due to resistance losses (on the order of 25 percent of the cell voltage) caused by ion transport between the components, making scale-up to commercially relevant levels impractical.


In electrochemical systems, broadly speaking, an oxidation reaction at the anode and a reduction reaction at the cathode create a driving force for electrons to flow, thereby converting chemical energy into electrical energy or vice-versa. As a proof-of-concept, the researchers electrochemically coupled Shewanella oneidensis, an anaerobic bacterium, to an inorganic catalyst, tin dioxide (SnO2). At 2 nanometers thick, the silica membrane enabled current flow while blocking oxygen and other small molecule transport.


This study builds on previous work by Frei’s group in which they fabricated a square-inch sized artificial photosystem, in the form of an inorganic core-shell nanotube array, and by Ajo-Franklin’s group in which insight at the molecular level revealed how the outer cell membrane protein interacts with an inorganic oxide surface.



The MINERVA Center on Bio‐hybrid Complex Systems represents an interdisciplinary effort aimed at developing bio‐inspired hybrid structures that will be integrated into complex nano/micro systems that exhibit new chemical, physical and functional properties emerging from the nano scale ordering of the assemblies. The research addresses the synthesis and assembly of the components, the molecular nano/micro‐scale characterization of the hybrids and the tailoring of functional systems and devices adapting principles of biology.

The topics that are addressed by the center include:

  • Smart bio‐hybrid systems that adapt tailored macroscopic functions originating from molecular or nano‐scale interactions. The systems are utilized for molecular machinery, circuitry, and logic operations.
  • Bio‐inspired (biomolecular and biomimetic) energy conversion and storage systems.
  • Bioelectronics and phtonics biohybrid systems; Interfacing biomolecules with nanoparticles (nanowires/nanotubes) or electronic elements (electrodes, transistors) for the construction of bioelectronic, or optobioelectronic devices.
  • Single cell studies addressing protein‐cell and intercellular interactions, and probing cell interactions with microenviroments. Studies include incorporation of bio‐inspired molecular machineries/nanoparticles into cells, and integration of live cells with solid‐state platforms.
  • Design of stimuli-regulated biomolecule/nano (micro) container systems for controlled delivery of drugs.


The assembly of such bio‐inspired systems involves challenging fundamental issues and holds great technological promises. Such bio‐inspired hybrid systems are expected to provide innovative solar energy conversion and storage systems, smart materials for nano‐medicine, innovative analytical sensors, bioelectronic and biofuel cells, and nano (micro) robotic systems.


These scientific challenges may only be resolved by an interdisciplinary research team involving experts in biophysics, chemistry, biology and material science. The MINERVA Center for Bio-hybrid Complex Systems assembled a team of established scientists bridging the various disciplines with the vision that a collaborative research leads to a synergistic output of innovative science with important practical implications.



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