Wyss Institute team unveils a low-cost, portable method to manufacture biomolecules for a wide range of vaccines, other therapies as well as diagnostics
Even amidst all the celebrated advances of modern medicine, basic life-saving interventions are still not reaching massive numbers of people who live in our planet’s most remote and non-industrialized locations. The World Health Organization states that one half of the global population lives in rural areas. And according to UNICEF, last year nearly 20 million infants globally did not receive what we would consider to be basic vaccinations required for a child’s health.
These daunting statistics are largely due to the logistical challenge of transporting vaccines and other biomolecules used in diagnostics and therapy, which conventionally require a “cold chain” of refrigeration from the time of synthesis to the time of administration. In remote areas lacking power or established transport routes, modern medicine often cannot reach those who may need it urgently.
A team of researchers at Harvard’s Wyss Institute for Biologically Inspired Engineering has been working toward a paradigm-shifting goal: a molecular manufacturing method that can produce a broad range of biomolecules, including vaccines, antimicrobial peptides and antibody conjugates, anywhere in the world, without power or refrigeration.
Now, in a new paper published September 22 in Cell journal, the team has unveiled what they set out to deliver, a “just add water” portable method that affordably, rapidly, and precisely generates compounds that could be administered as therapies or used in experiments and diagnostics.
“The ability to synthesize and administer biomolecular compounds, anywhere, could undoubtedly shift the reach of medicine and science across the world,” said Wyss Core Faculty member James Collins, Ph.D., senior author on the study, who is also Professor of Medical Engineering & Science and Professor of Biological Engineering at the Massachusetts Institute of Technology (MIT)’s Department of Biological Engineering. “Our goal is make biomolecular manufacturing accessible wherever it could improve lives.”
The approach, called “portable biomolecular manufacturing” by Collins’ team, which also included Neel Joshi, Ph.D., a Wyss Core Faculty member and Associate Professor of Chemical and Biological Engineering at Harvard’s John A. Paulson School of Engineering and Applied Sciences (SEAS), hinges on the idea that freeze-dried pellets containing “molecular machinery” can be mixed and matched to achieve a wide variety of end-products. By simply adding water, this molecular machinery can be set in motion.
To activate the biomolecular manufacturing process, freeze-dried components need simply be rehydrated (as seen in this mock demonstration). Credit: Wyss Institute at Harvard University
Compounds manufactured using the method could be administered in several ways to a patient, including injection, oral doses or topical applications. As described in the study, a vaccine against diphtheria was synthesized using the method and shown to successfully induce an antibody response against the pathogen in mice.
Subsequently, the team envisions that the method could be employed to create batches of tetanus or flu shots routinely manufactured in remote clinics. Vaccines against emerging infectious disease outbreaks could quickly be mobilized in the field to contain spiraling epidemics. Episodes of food poisoning could be dosed orally with the production of neutralizing antibodies produced on the spot. Flesh wounds susceptible to infection could be applied with topical antimicrobial peptides generated on demand. In these manners, the team’s approach could be leveraged to design a vast number of different lifesaving measures.
The approach is built upon work described in a seminal 2014 paper also published in Cell, when the team demonstrated that transcription and translation machinery could function in vitro, without being inside living cells, inside freeze-dried slips of ordinary paper embedded with synthetic gene networks.
The Wyss Institute team envisions that the compounds created using the portable manufacturing method could be administered to patients in a variety of ways, including injection (as seen in this mock demonstration), oral delivery, and topical application. Credit: Wyss Institute at Harvard University
Building off that work, the novel manufacturing method employs two types of freeze-dried pellets containing different kinds of components. The first kind of pellet contains the cell-free “machinery” that will synthesize the end product. The second kind contains DNA instructions that will tell the “machinery” what compound to manufacture. When the two types of pellets are combined and rehydrated with water, the biomolecular manufacturing process is triggered. The second type of pellet can be customized to produce a wide range of final products.
Since they are freeze-dried, the pellets are extremely stable and safe for long-term storage at room temperature for up to and potentially beyond one year.
“This approach could — with very little training — put therapeutics and diagnostic tools in the hands of clinicians working in remote areas without power,” said Keith Pardee, Ph.D., a co-first author on the study who was a Wyss Research Scientist and is now an Assistant Professor in the Leslie Dan Faculty of Pharmacy at the University of Toronto. “Currently, distribution of life-saving doses of protein-based preventative and interventional medicines are often restricted by access to an uninterrupted chain of cold refrigeration, which many areas of the world lack.”
The cost of the approach, at roughly three cents per microliter, could also give access to biomolecular manufacturing to researchers and educators who lack access to wet labs and other sophisticated equipment, impacting basic science beyond the immediately apparent promise in clinical applications.
“Synthetic biology has been harnessed to increase efficiency of manufacturing of biological products for medical and energy applications in the past, however, this new breakthrough utterly changes the application landscape,” said Wyss Core Faculty member Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and the Vascular Biology Program at Boston Children’s Hospital, as well as Professor of Bioengineering at Harvard’s SEAS. “It’s really exciting because this new biomolecular manufacturing technology potentially offers a way to solve the cold chain problem that still restricts delivery of vaccines and other important medical treatments to patients in the most far-flung corners of the world who need them the most.”
Powered by a chemical reaction controlled by microfluidics, 3D-printed ‘octobot’ has no electronics
A team of Harvard University researchers with expertise in 3D printing, mechanical engineering, and microfluidics has demonstrated the first autonomous, untethered, entirely soft robot. This small, 3D-printed robot — nicknamed the octobot — could pave the way for a new generation of completely soft, autonomous machines.
Soft robotics could revolutionize how humans interact with machines. But researchers have struggled to build entirely compliant robots. Electric power and control systems — such as batteries and circuit boards — are rigid and until now soft-bodied robots have been either tethered to an off-board system or rigged with hard components.
Robert Wood, the Charles River Professor of Engineering and Applied Sciences and Jennifer A. Lewis, the Hansjorg Wyss Professor of Biologically Inspired Engineering at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) led the research. Lewis and Wood are also core faculty members of the Wyss Institute for Biologically Inspired Engineering at Harvard University.
“One long-standing vision for the field of soft robotics has been to create robots that are entirely soft, but the struggle has always been in replacing rigid components like batteries and electronic controls with analogous soft systems and then putting it all together,” said Wood. “This research demonstrates that we can easily manufacture the key components of a simple, entirely soft robot, which lays the foundation for more complex designs.”
The research is described in the journal Nature.
“Through our hybrid assembly approach, we were able to 3D print each of the functional components required within the soft robot body, including the fuel storage, power and actuation, in a rapid manner,” said Lewis. “The octobot is a simple embodiment designed to demonstrate our integrated design and additive fabrication strategy for embedding autonomous functionality.”
Octopuses have long been a source of inspiration in soft robotics. These curious creatures can perform incredible feats of strength and dexterity with no internal skeleton.
Harvard’s octobot is pneumatic-based — powered by gas under pressure. A reaction inside the bot transforms a small amount of liquid fuel (hydrogen peroxide) into a large amount of gas, which flows into the octobot’s arms and inflates them like a balloon.
“Fuel sources for soft robots have always relied on some type of rigid components,” said Michael Wehner, a postdoctoral fellow in the Wood lab and co-first author of the paper. “The wonderful thing about hydrogen peroxide is that a simple reaction between the chemical and a catalyst — in this case platinum — allows us to replace rigid power sources.”
To control the reaction, the team used a microfluidic logic circuit based on pioneering work by co-author and chemist George Whitesides, the Woodford L. and Ann A. Flowers University Professor and core faculty member of the Wyss. The circuit, a soft analog of a simple electronic oscillator, controls when hydrogen peroxide decomposes to gas in the octobot.
“The entire system is simple to fabricate, by combining three fabrication methods — soft lithography, molding and 3D printing — we can quickly manufacture these devices,” said Ryan Truby, a graduate student in the Lewis lab and co-first author of the paper.
The simplicity of the assembly process paves the way for more complex designs. Next, the Harvard team hopes to design an octobot that can crawl, swim and interact with its environment.
“This research is a proof of concept,” Truby said. “We hope that our approach for creating autonomous soft robots inspires roboticists, material scientists and researchers focused on advanced manufacturing,”
Learn more: The first autonomous, entirely soft robot
New system surpasses efficiency of photosynthesis
The days of drilling into the ground in the search for fuel may be numbered, because if Daniel Nocera has his way, it’ll just be a matter of looking for sunny skies.
Nocera, the Patterson Rockwood Professor of Energy at Harvard University, and Pamela Silver, the Elliott T. and Onie H. Adams Professor of Biochemistry and Systems Biology at Harvard Medical School, have co-created a system that uses solar energy to split water molecules and hydrogen-eating bacteria to produce liquid fuels.
The paper, whose lead authors include postdoctoral fellow Chong Liu and graduate student Brendan Colón, is described in a June 3 paper published in Science.
“This is a true artificial photosynthesis system,” Nocera said. “Before, people were using artificial photosynthesis for water-splitting, but this is a true A-to-Z system, and we’ve gone well over the efficiency of photosynthesis in nature.”
While the study shows the system can be used to generate usable fuels, its potential doesn’t end there, said Silver, who is also a founding core member of the Wyss Institute at Harvard University.
The Wyss Institute for Biologically Inspired Engineering is a cross-disciplinary research institute at Harvard University which focuses on developing new bioinspired materials and devices for applications in healthcare, manufacturing, robotics, energy, and sustainable architecture.
The Institute has two sites: one in the Center for Life Sciences Boston building in Boston’s Longwood Medical Area, and one on Harvard’s main campus in Cambridge, Massachusetts. The Wyss Institute was launched in January 2009 with a $125 million gift to Harvard—the largest single philanthropic gift in its history—from Hansjörg Wyss.
The Institute works as an alliance among Harvard Medical School, Harvard School of Dental Medicine, Harvard School of Engineering and Applied Sciences, Harvard Faculty of Arts and Sciences, Children’s Hospital Boston, Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center, Boston University, Brigham and Women’s Hospital, Massachusetts General Hospital, Spaulding Rehabilitation Hospital, and the University of Massachusetts Medical School. Translating technological discoveries into commercial products and therapies is an important part of the organization’s mission.
The Latest Updated Research News:
Wyss Institute research articles from Innovation Toronto
- Bionic leaf turns sunlight into liquid fuel at 10 times the efficiency of photosynthesis – June 3, 2016
- Soft clothing-like exosuits to increase the wearer’s strength and endurance – May 23, 2016
- Using static electricity, RoboBees can land and stick to surfaces – May 20, 2016
- 3D Printing metal in midair for customized electronic and biomedical devices – May 20, 2016
- Finding Zika one paper disc at a time in 2 to 3 hours – May 7, 2016
- Scaling up tissue engineering with a new bioprinting technique – March 14, 2016
- Imagine a house that could fit in a backpack: A foldable material that can change size, volume and shape – March 12, 2016
- Pulling water from thin air – February 25, 2016
- Biosensors on demand by designer proteins – February 14, 2016
- Sensing the future of living detectors and bioproduction – January 31, 2016
- “Kill switches” shut down engineered bacteria – December 16, 2015
- Creating a new vision for multifunctional materials – November 29, 2015
- Gene drive reversibility introduces new layer of biosafety – November 18, 2015
- Microbiomes could hold keys to improving life as we know it – October 30, 2015
- Printing lightweight, flexible, and functional materials – September 22, 2015
- Robotic insect mimics Nature’s extreme moves – August 1, 2015
- A practical gel that simply “clicks” for biomedical applications – May 2, 2015
- A slippery surface that can repel almost everything – March 29, 2015
- New Material Stops Biofilm Formation – February 14, 2015
- A Breakthrough in Artificial Photosynthesis – February 11, 2015
- Injectable 3D vaccines could fight cancer and infectious diseases – December 9, 2014
- Airway muscle-on-a-chip mimics asthma – September 29, 2014
- A Wearable Robot Suit That Will Add Power To Your Step – September 11, 2014
- Cheap and compact medical testing – August 19, 2014
- A self-organizing thousand-robot swarm – August 15, 2014
- Carbon-fiber epoxy honeycombs mimic the material performance of balsa wood – June 26, 2014
- The concept of organs on a chip opens the possibility of realistically studying human organs without the use of patients or animal testing – June 25, 2014
- Researchers use light to coax stem cells to repair teeth – May 29, 2014
- ‘Heart disease-on-a-chip’ – May 12, 2014
- Bone marrow-on-a-chip unveiled – no animal testing needed – May 6, 2014
- Smart DNA nanorobots – April 23, 2014
- Wyss Institute awarded DARPA contract to further advance sepsis therapeutic device
- Electrical generators driven by changes in humidity from sun-warmed ponds and harbors
- Bio-Inspired Robotic Device Could Aid Ankle-Foot Rehabilitation
- Programming smart molecules: Could Make Chemical Reactions Intelligent
- Programmable glue made of DNA directs tiny gel bricks to self-assemble
- Cross-Disciplinary Team From Harvard and Dana-Farber Brings Novel Therapeutic Cancer Vaccine to Human Clinical Trials
- New coating turns ordinary glass into superglass
- Lifelike cooling for sunbaked windows
- Dodging antibiotic side effects
- Soft Exosuit
- High-octane bacteria could ease pain at the pump
- A shot in the arm for old antibiotics
- Printing Tiny Batteries
- Robotic insects make first controlled flight
- Cry me a river of possibility: Scientists design new adaptive material inspired by tears
- Scientists Notch a Win in War Against Antibiotic-Resistant Bacteria
- Prefabricated healing kit: Injectable sponge delivers drugs, cells, and structure
- “Lung-on-a-chip” sets stage for next wave of research to replace animal testing
- Writing the Book in DNA
- New coating evicts biofilms for good
- Smart suit improves physical endurance
- Artificial jellyfish created from rat heart tissue and silicone
- DNA robot could kill cancer cells
- In New Mass-Production Technique, Robotic Insects Spring to Life
- Cheap, biodegradable, biocompatible “Shrilk” is a potential plastic replacement
- Carnivorous Plant Inspires Coating That Resists Just About Any Liquids
- Organs-on-a-Chip for Faster Drug Development
- Researchers Create Self-Assembling Nanodevices That Move and Change Shape on Demand
- Fingernail-sized implant successfully eliminates tumors in mammals
Lightweight suit to increase the wearer’s strength and endurance
For decades engineers have built exoskeletons that use rigid links in parallel with the biological anatomy to increase the wearer’s strength and endurance, and to protect them from injury and physical stress. In recent years, a number of systems have been developed that show strong commercial potential for helping spinal-cord injury patients walk, or helping soldiers carry heavy loads. In these systems, there is an exoskeleton structure in parallel with the wearer’s skeletal structure that is typically connected at a few locations on the body using straps or belts. These devices use motors or elastic materials to assist with joint movements, thereby enhancing human power. However, exoskeletons often fail to allow the wearer to perform his or her natural joint movements, are generally heavy, and can hence cause fatigue.
The Wyss Solution
Targeting a specific set of applications where a wearer needs some partial assistance from a robot, Wyss Institute researchers are pursuing a new paradigm: the use of soft clothing-like “exosuits.” An exosuit does not contain any rigid elements, so the wearer’s bone structure must sustain all the compressive forces normally encountered by the body — plus the forces generated by the exosuit. The suit, which is composed primarily of specially designed fabrics, can be significantly lighter than an exoskeleton since it does not contain a rigid structure. It also provides minimal restrictions to the wearer’s motions, avoiding problems relating to joint misalignment.
Exosuits exemplify a new class of applications for soft robotics, an emerging field that combines classical robotic design and control principles with active soft materials.
Synthetic biology technique could make it safer to put engineered microbes to work outside the lab
Many research teams are developing genetically modified bacteria that could one day travel around parts of the human body, diagnosing and even treating infection. The bugs could also be used to monitor toxins in rivers or to improve crop fertilization.
However, before such bacteria can be safely let loose, scientists will need to find a way to prevent them from escaping into the wider environment, where they might grow and cause harm.