Technowave

Specially engineered cells arrange themselves into three-dimensional microtissues.

Cells coated with sticky bits of DNA can self-assemble into functional three-dimensional microstructures. This bottom-up approach to tissue engineering, developed by scientists at Lawrence Berkeley National Laboratory and the University of California, Berkeley, provides a new solution to one of field’s biggest problems: the creation of multicellular tissues with defined structures. Unlike top-down methods, in which scientists build cell structures on scaffolds, the new technique allows tissue engineers to dictate the precise geometric interactions of individual cells.

Researchers started with two cell types–one that secretes a protein, called a growth factor, which the other requires in order to grow. Coauthor Zev Gartner, now a pharmaceutical chemist at the University of California, San Francisco, decorated the cells with snippets of single-stranded DNA, attached using specialized sugars incorporated into the cell membrane. The two cell types carried complementary strands of DNA, which acted as a sort of Velcro. When the different cells were combined, their complementary DNA fragments joined into double strands, linking the cells together. Joined to their protein producing partners, the protein-dependent cells flourish. Without the DNA coating, the two cell types can’t communicate, and the dependent cells die.

By varying the relative concentrations of the two cell types, the researchers could maneuver the cells into particular configurations. For instance, when the cells were combined in a one-to-one ratio, they simply formed pairs. But when the growth-factor-dependent cells vastly outnumbered their counterparts, they formed characteristic three-dimensional clusters with a single growth-factor-secreting cell in the center. The results appeared Monday in the early online edition of Proceedings of the National Academy of Sciences.

“This approach provides a new way of recreating tissue complexity,” says Ali Khademhosseini, an assistant professor at Harvard-MIT’s Division of Health Sciences and Technology and Harvard Medical School, who was not involved in the study. Most tissue-engineering methods produce three-dimensional structures with the help of scaffolding materials.

Once the microstructures had formed, Gartner and his colleague Carolyn Bertozzi, director of the Molecular Foundry nanoscience research facility at Berkeley Lab, trapped them in a gel and imaged them in three dimensions using a fluorescence microscope. Because the cell-surface DNA isn’t stable in the long term, it’s not yet clear how long the structures will hold up on their own. The researchers are currently investigating whether the linked cells will begin to generate their own natural adhesion molecules to keep them attached once the DNA links are gone.

So far these microstructures are rudimentary–far from the structural sophistication of a whole organ. But by tweaking the ratio of cell types, the density of DNA on the cells’ surfaces, and the complexity of the DNA sequences, Gartner and Bertozzi hope to build larger and more intricate assemblies. “By playing around with these variables, we can bias the type of structure that we’re making,” says Gartner.

Combining different battery technologies could improve vehicle performance and reduce costs.

The race is on to find the ideal battery chemistry for plug-in hybrids and all-electric vehicles, but a startup in Indiana believes that a combination of different storage technologies might be the best way to improve vehicle performance and reduce cost. The company’s technology allows vehicles to run on a combination of fuel cells, ultracapacitors, and old-fashioned lead-acid batteries.

Noblesville-based Indy Power Systems has developed an energy management system for vehicles that can quickly switch between two or more energy sources, even when their voltages are different. “It’s basically a switch that directs energy in any amount and any direction,” says Steve Tolen, chief executive officer and founder of Indy Power, which operates out of Purdue Research Park. “The hardware handles the switching, and the software handles the timing and amounts.”

Tolen says that the power electronics package–called the Multi-Flex Energy Management System–is only slightly larger than a laptop computer. He describes it as a custom, software-controlled, DC-to-DC converter that’s bidirectional and variable.

“Imagine adding hot and cold water to a tub. We can add a variable amount of hot and a variable amount of cold in different volumes to match the outflow of the drain, which can also be variable,” Tolen explains. “In other words, the motor can ask for different amounts of current, and we can provide that, and in different ratios from the two (or more) power sources, regardless of the voltage of the power sources.”

For example, an electric vehicle could have both lead-acid and lithium-ion battery packs. Advanced lead-acid batteries may be cheaper, but they are also heavier and deteriorate more quickly if subjected to regular depletion and recharging. Lithium-ion batteries are generally more robust and lighter but are far more expensive. Combining the two means that you can use less of each. And just as important, says Tolen, the two chemistries can be balanced against each other to optimize performance. For example, the lithium-ion battery can be used to relieve stress on the lead-acid battery and extend its life, and vice versa.

Reza Iravani, a professor of electrical and computer engineering at the University of Toronto, says that Indy Power’s system is part of a trend toward greater emphasis on hybrid storage. For example, he says, Researchers in Australia have designed a car-battery system that combines lead-acid technology with supercapacitors, resulting in a fourfold increase in the life of the lead-acid batteries.

A California biotech company is engineering microbes to produce cheap biofuels that could outcompete ethanol.

Stroll the streets of San Francisco and you’re likely to overhear someone talking about biofuels. It’s the latest technology wave to hit the Bay Area, and scientists and investors are swarming toward any startup claiming a better way to make ethanol or biodiesels. Amyris Biotechnologies may actually have found one. Having previously reengineered microbes so that they would produce a malaria drug, the company is now drawing on its expertise at creating efficient bacterial factories to cheaply churn out novel types of biofuels.

Amyris is one of the first companies to spring from the relatively new field of synthetic biology. Unlike the conventional genetic engineering currently used in the manufacture of antibiotics and protein drugs such as insulin, synthetic biology involves hacking the entire metabolic system–changing the structure of some proteins, altering the expression of others, and adding in genes from other organisms–to create an efficient microbial machine. “We think of biological components as parts you assemble and try to get to function as a whole,” says Jay Keasling, a bioengineer at the University of California, Berkeley, and one of Amyris’s cofounders.

Plants and microbes naturally make small quantities of chemicals called terpenoids, which are the precursors of myriad products, including some pharmaceuticals and fuels. Several years ago, after developing new ways to boost bacteria’s production of terpenoids, Keasling and three of his postdoctoral students founded Amyris to commercialize their work.

For its first project, the company selected artemisinin, a potent malaria drug derived from the sweet wormwood tree (see TR10 2005). By tinkering with yeast’s metabolic processes, Keasling and his colleagues were able to boost its production of an artemisinin precursor a million-fold. After just two years of work, they are close to meeting their final goal for the drug–producing it in industrial quantities at prices affordable to developing nations. Now, having created microbial factories that can cheaply churn out carbon-based molecules, the group has turned its attention to biofuels.

Making fuel is different from making medicine. In most cases, pharmaceutical companies aren’t concerned with how efficiently they make their drugs because they know they can charge premium prices for them. New fuels, on the other hand, must compete in price with petroleum. Rather than trying to find better ways to make ethanol–the aim of most new biofuel efforts–the researchers chose to create entirely novel biofuels, guided by their own ideas about what a fuel might look like if designed from scratch. “We looked at the Merck Index and said, If you could pick any molecule to use as fuel, what would you pick?” says Jack Newman, one of Amyris’s cofounders and vice president of research.

The researchers selected several candidate compounds based on their energy content (ethanol has only 70 percent the energy of gasoline), their volatility (an ideal fuel shouldn’t evaporate too fast), and their solubility in water (unlike ethanol, a water-insoluble fuel could be piped around the country like petroleum). After narrowing the list by determining which fuels could be both produced in the lab and used in today’s engines, they were left with a selection of compounds including replacements for both diesel and jet fuel. “We’ve tested a lot of fuels with fantastic properties,” says Neil Renninger, Amyris cofounder and vice president of development.

Amyris scientists are now designing metabolic pathways that yield these compounds and tinkering with them to make production as efficient as possible. “You have to walk down a cost curve of production,” says Renninger. “At the bottom, you get a product so cheap you can burn it.”

While the company is still a long way from having a practical biofuel, its progress will be under close watch. As ethanol is being used more and more for transportation fuel, biofuels have captured the attention of investors. Indeed, in 2001, when Keasling and colleagues first thought about making biofuels, Amyris found very little investor interest. That has changed. “We went out with the aim of raising $7 million [during a 2006 round of financing] and ended up with $20 million,” says Newman. “We had to turn down multiple investors.”

Genetically modified algae could be efficient producers of hydrogen and biofuels.

Algae are a promising source of biofuels: besides being easy to grow and handle, some varieties are rich in oil similar to that produced by soybeans. Algae also produce another fuel: hydrogen. They make a small amount of hydrogen naturally during photosynthesis, but Anastasios Melis, a plant- and microbial-biology professor at the University of California, Berkeley, believes that genetically engineered versions of the tiny green organisms have a good shot at being a viable source for hydrogen.

Melis has created mutant algae that make better use of sunlight than their natural cousins do. This could increase the hydrogen that the algae produce by a factor of three. It would also boost the algae’s production of oil for biofuels.

The new finding will be important in maximizing the production of hydrogen in large-scale, commercial bioreactors. In a laboratory, Melis says, “[we make] low-density cultures and have thin bottles so that light penetrates from all sides.” Because of this, the cells use all the light falling on them. But in a commercial bioreactor, where dense algae cultures would be spread out in open ponds under the sun, the top layers of algae absorb all the sunlight but can only use a fraction of it.

Melis and his colleagues are designing algae that have less chlorophyll so that they absorb less sunlight. That means more light penetrates into the deeper algae layers, and eventually, more cells use the sunlight to make hydrogen.

The researchers manipulate the genes that control the amount of chlorophyll in the algae’s chloroplasts, the cellular organs that are the centers for photosynthesis. Each chloroplast naturally has 600 chlorophyll molecules. So far, the researchers have reduced this number by half. They plan to reduce the size further, to 130 chlorophyll molecules. At that point, dense cultures of algae in big bioreactors would make three times as much hydrogen as they make now, Melis says.

“If you can increase the productivity by means of thinning out the [chlorophyll], it’s going to affect any product that you make,” says Rolf Mehlhorn, an energy technologist at the Lawrence Berkeley National Laboratory. Algae that use sunlight more effectively would produce more oil, he says. Startups such as Solix Biofuels, based in Fort Collins, CO, and LiveFuels, based in Menlo Park, CA, are trying to extract oil from algae; the oil can be refined to make diesel and jet fuel.

The process is still at least five years from being used for hydrogen generation. Researchers will first have to increase the algae’s capacity to produce hydrogen. During normal photosynthesis, algae focus on using the sun’s energy to convert carbon dioxide and water into glucose, releasing oxygen in the process. Only about 3 to 5 percent of photosynthesis leads to hydrogen. Melis estimates that, if the entire capacity of the photosynthesis of the algae could be directed toward hydrogen production, 80 kilograms of hydrogen could be produced commercially per acre per day.

A new solar cell is 27 percent more efficient without being more expensive to make.

An MIT researcher has found a way to significantly improve the efficiently of an important type of silicon solar cells while keeping costs about the same. The technology is being commercialized by a startup in Lexington, MA, called 1366 Technologies, which today announced its first round of funding. Venture capitalists invested $12.4 million in the company.

1366 Technologies claims that it improves the efficiency–a measure of the electricity generated from a given amount of light–of multicrystalline silicon solar cells by 27 percent compared with conventional ones. The company’s efficiency and cost claims are based on results from small solar cells (about two centimeters across) made in the lab of Emanuel Sachs, a professor of mechanical engineering at MIT, who is one of the company’s founders. 1366 Technologies is building a pilot-scale manufacturing plant that will make full-sized solar cells (about 15 centimeters across). Within a year, the company will decide whether its pilot-plant results justify building a factory for commercial production, Sachs says.

Commercial solar cells made from multicrystalline silicon are normally far less efficient than more expensive ones made from single-crystal silicon, but they’re cheaper. The 27 percent improvement will bring multicrystalline cells to efficiencies about the same as single-crystal cells–around 19.5 percent–at the lower costs. So, if the technology successfully scales up, Sachs says, it could significantly bring down the cost of solar electricity. Sachs says that today, solar cells cost about $2.10 per watt generated. When manufactured at a commercial scale, the first cells incorporating his new technology will cost $1.65 per watt. Planned improvements will bring down this cost to about $1.30 a watt, he says. To compete with coal, the cost will need to come down to about $1 a watt, something that Sachs predicts can be achieved by 2012 with further improvements in antireflection coatings and other anticipated advances.

The company’s first prototype solar cells include three key innovations to improve efficiency. The first is a method for adding texture to the surface of the cells that allows the silicon to absorb more light, a trick that’s been used before with single-crystalline devices but has been difficult to implement with multicrystalline silicon. The rough surface causes light to bend as it enters the cell so that when it encounters the back of the cell, it doesn’t reflect right back out; rather, it bounces off at a low angle and remains inside the slab of silicon. The longer the light remains within the silicon, the greater the chance that it will be absorbed and converted into electricity.