The Center for Bioengineering

Countering Biothreats with Nanoscale Solutions

Micro- and nanotechnology includes materials, devices and systems that require microfabricated components on the order of one micrometer or one nanometer. The Center for Bioengineering’s expertise spans micro- and nanofabrication processes, microelectromechanical systems, electronics, photonics, micro- and nanostructures, implantable devices, and micro- and nanoactuators.

Recently, these nanoscale technologies played a key role in efforts to develop next-generation material to protect warfighters and first responders from biological and chemical warfare agents.

LLNL researchers and engineers Francesco Fornasiero, Ngoc Bui, Eric Meshot, Chiatai Chen, José Peña, and Kuang Jen Wu are pioneering the use of carbon nanotubes — with pores just a few nanometers wide — to create a base layer material that simultaneously provides biological threat protection and permeability to water vapor and which can be paired with a "smart" surface layer that guards against chemical agents. The team, with support from the Defense Threat Reduction Agency and the Laboratory Directed Research and Development Program, has already attained a crucial milestone in developing this next-generation protective garment by demonstrating that the proposed base layer is highly protective yet remarkably breathable. Read the full story about the technology here.

Other carbon nanotube applications under study include biomimetic membranes with high throughput and high selectivity that can enable ultra-fast dialysis for patients. Read that story here.

Combined Success with UCSF

A strong relationship with bioengineers, neuroscientists, and surgeons nationwide is critical to LLNL’s research efforts. For example, Livermore’s microfabrication know-how complemented clinical science expertise at UCSF while developing a method to implant flexible probes into deep brain tissue.

One therapeutic use of the flexible probe designs is deep brain stimulation (DBS). Currently used to treat some neurological disorders such as Parkinson’s disease, essential tremor, and epilepsy, DBS is also being investigated as a treatment for depression, neuropsychiatric disorders, PTSD, traumatic brain injury, and chronic pain. In DBS, surgically implanted electrical leads deliver pulses to specific brain tissue to disrupt certain electrical signals associated with a disorder; however the current technique lacks precision and includes undesirable side effects.

LLNL's effort to better understand DBS and enhance its effectiveness is part of DARPA’s Systems-Based Neurotechnology for Emerging Therapies (SUBNETS) program, part of the BRAIN Initiative. Read the full article.

Brain on a Chip

Some of our most significant advances are very tiny, such as a brain-on-a-chip device that records the neural activity of living brain cell cultures, enabling researchers to study the function of the human brain—outside of the body.

Using a 3D microelectrode array platform, researchers can keep thousands of human-derived neurons alive, networked, and communicating, while non-invasively recording their electrical activity. The device will advance research aimed at modeling disease or infections, drug discovery, and developing countermeasures for chemical or biological agent exposure.

In one of its first usages, LLNL scientists compared drug responses in the brains of rodents to drug responses of brain cells cultured in Lab-developed "brain-on-a-chip" devices — providing a critical first step to validating chip-based brain platforms.

With a validated device in place, scientists moved on to modeling the temporal dynamics of neuronal cultures, paving the way to use the 3D brain-on-a-chip to screen therapeutic compounds and to develop human-relevant models of neuronal cultures for diseases and disorders such as traumatic brain injury — and perhaps find ways of re-establishing normal brain function in TBI patients.

3D Printed COVID Swabs

LLNL Engineering joined the fight against COVID-19 in 2020, shortly after the pandemic began. In addition to rapid antibody design and emergency-use ventilator fabrication, we worked on consumables, such as N95 mask reuse sterilization and 3D printed nasopharyngeal swabs. A special issue of the Materials Research Society (MRS) Bulletin focuses on materials science innovation in response to the pandemic and offers a brief overview of consumables produced in the context of COVID-19 and the need the pandemic has elicited for rapid iteration and testing of medical technologies. Some of the need for rapid iteration was occasioned by manufacturing and supply chain issues, and some was necessitated by a need for more accessible or more rapid diagnostics than the PCR tests that have become the go-to for reliable COVID testing. At LLNL, the production of nasopharyngeal testing swabs was among the endeavors undertaken to address supply shortages, and innovation in the production of nasopharyngeal swabs occasioned the need for a quantitative assessment of their performance as well as robust testing protocols for general use. Led by Tooker and Materials Engineering Division Leader Chris Spadaccini, a protocol developed at LLNL aimed to provide a reliable, quantitative set of methods for understanding the aspects of swabs that are crucial to reliable COVID testing: collecting enough of a sample for RNA to be extracted from it and producing structural soundness that doesn’t come at the expense of flexibility and patient comfort. Read the full story.

LLNL develops 'stopgap' ventilator for COVID-19 patients

While hospitals across the U.S. faced a possible shortage of mechanical ventilators due to COVID-19, a self-assembled team at LLNL worked tirelessly to prototype a simple ventilator design for quick and easy assembly from available parts.

They first looked at CPAP machines — breathing aids commonly used to treat sleep apnea — as a potential viable option for sourcing components. When that proved unfeasible, the team started from scratch, studying ventilator design and manufacturing as well as talking to medical professionals. The team includes 20 scientists and engineers from the Lab’s Computing, Engineering and Physical and Life Sciences directorates who, before shelter-in-place orders went into effect, were working on national security efforts.

They received help from experts in the field, including intensive care unit doctors from the University of California, San Francisco, researchers from Colorado State University, associates of Homewood Consulting of Birmingham, Alabama, the University of Alabama at Birmingham and the Children’s of Alabama hospital, as well as the director of pediatric pulmonary medicine at Atrium Health in Charlotte. With many team members working around the clock, the effort produced a prototype dubbed the "Novel Emergency Response Ventilator" (NERVe), the design is derived from proven concepts and contains parts that are not being used by commercial ventilator manufacturers, to avoid disrupting already thin supply chains.

It is designed to meet the functional requirements of COVID-19 patients requiring mechanical ventilation, including a simple user interface, air flow circuits for inhalation and exhalation, and alarms to notify physicians if air pressures get too low. It can operate in a continuous ventilation mode — common for late-stage COVID-19 patients — but can adapt to patients who spontaneously breathe on their own. Read the full story.

Watch a video about the prototyping process.

LLNL GUIDE Rapid Response Platform Employed by DoD in Omicron Response

Between 2020 and 2022, engineers at LLNL used machine learning to create antibodies against Omicron, which has had immediate clinical interest and investment.

Led by Dan Faissol and Tom Desautels of the Computational Engineering Division, the work has made use of LLNL's largest computer, Sierra, to advance very quickly in the face of the 2021-2022 Omicron variant of COVID-19. Named "GUIDE," the project is an AI-enabled, rapid biologic countermeasure design consortium, led by LLNL and with input from Los Alamos and Sandia National Labs, plus representatives from industry and academia. GUIDE was initiated when primary antibody therapy CoV-2130 proved ineffective against Omicron, requiring re-targeting of this antibody product. Within just two and a half weeks, the LLNL team provided ~200 antibody sequences that were predicted to be effective and manufacturable (and which were under testing as of March 2022). This was done via an extensive campaign that used over 1 million GPU hours, including first use of Sierra in non-defense application.

In the video below, LLNL scientists explain how they are using antibodies from the nearly 20 year old SARS-1 outbreak to engineer antibodies for COVID-19. The team draws upon expertise at LLNL in biology, high-performance computing, and machine learning to create possible countermeasures for COVID-19 and to prepare for future outbreaks.

Thin-filmed Electrodes Provide Key Insights

In a study at UCSF, neurologists placed thin-film multi-electrode arrays developed at LLNL on the exposed hippocampus of patients undergoing epilepsy-related surgeries. The devices enabled the researchers to detect traveling waves of neural activity moving across the hippocampal surface and identify new properties about them — including bi-directionality during behavioral tasks — providing an enhanced understanding of human cognition.

Thin-film electrodes developed at LLNL have been used in human patients at UCSF, generating never-before-seen recordings of brain activity in the hippocampus, a region responsible for memory and other cognitive functions.

In a study published in Nature Communications, surgeons at UCSF placed the flexible arrays on the brains of a group of patients while they were already undergoing epilepsy-related surgery. They recorded electrical signals across the exposed hippocampus while some patients were under anesthesia and others were awake, and conscious patients were given visual cues and spoke words while their neural activity was recorded. This approach allowed the researchers to detect traveling waves moving across the hippocampal surface and identify new properties about them, including how they may contribute to human cognition. Read the full article.