Nano power: An electron-microscope image of 40-nanometer-wide rod-shaped particles that make up a promising battery material.
Credit: Arumugam Manthiram, University of Texas at Austin

Researchers show a low-cost route to making materials for advanced batteries in electric cars and hybrids

By Kevin Bullis, July 30, 2008, MIT Technology Review – A new way to make advanced lithium-ion battery materials addresses one of their chief remaining problems: cost. Arumugam Manthiram, a professor of materials engineering at the University of Texas at Austin, has demonstrated that a microwave-based method for making lithium iron phosphate takes less time and uses lower temperatures than conventional methods, which could translate into lower costs.

Lithium iron phosphate is an alternative to the lithium cobalt oxide used in most lithium-ion batteries in laptop computers. It promises to be much cheaper because it uses iron rather than the much more expensive metal cobalt. Although it stores less energy than some other lithium-ion materials, lithium iron phosphate is safer and can be made in ways that allow the material to deliver large bursts of power, properties that make it particularly useful in hybrid vehicles.

Indeed, lithium iron phosphate has become one of the hottest new battery materials. For example, A123 Systems, a startup based in Watertown, MA, that has developed one form of the material, has raised more than $148 million and commercialized batteries for rechargeable power tools that can outperform conventional plug-in tools. The material is also one of the types being tested for a new electric car from General Motors.

But it has proved difficult and expensive to manufacture lithium iron phosphate batteries, which cuts into potential cost savings over more conventional lithium-ion batteries. Typically, the materials are made in a process that takes hours and requires temperatures as high as 700 °C.

Manthiram’s method involves mixing commercially available chemicals–lithium hydroxide, iron acetate, and phosphoric acid–in a solvent, and then subjecting this mixture to microwaves for five minutes, which heats the chemicals to about 300 °C. The process forms rod-shaped particles of lithium iron phosphate. The highest-performing particles are about 100 nanometers long and 25 nanometers wide. The small size is needed to allow lithium ions to move quickly in and out of the particles during charging and discharging of the battery.

To improve the performance of these materials, Manthiram coated the particles with an electrically conductive polymer, which was itself treated with small amounts of a type of sulfonic acid. The coated nanoparticles were then incorporated into a small battery cell for testing. At slow rates of discharge, the materials showed an impressive capacity: at 166 milliamp hours per gram, the materials came close to the theoretical capacity of lithium iron phosphate, which is 170 milliamp hours per gram. This capacity dropped off quickly at higher discharge rates in initial tests. But Manthiram says that the new versions of the material have shown better performance.

It’s still too early to say how much the new approach will reduce costs in the manufacturing of lithium iron phosphate batteries. The method’s low temperatures can reduce energy demands, and the fact that it is fast can lead to higher production from the same amount of equipment–both of which can make manufacturing more economical. But the cost of the conductive polymer and manufacturing equipment also needs to be figured in, and the process must be demonstrated at large scales. The process will also need to compete with other promising experimental manufacturing methods, says Stanley Whittingham, a professor of chemistry, materials science, and engineering at the State University of New York, at Binghamton.

Manthiram has recently published advances for two other types of lithium-ion battery materials and is working with ActaCell, a startup based in Austin, TX, to commercialize the technology developed in his lab. The company, which last week announced that it has raised $5.58 million in venture funding, has already licensed some of Manthiram’s technology, but it will not say which technology until next year.

TARGET HEALTH excels in Regulatory Affairs and works closely with many of its clients performing all FDA submissions. TARGET HEALTH receives daily updates of new developments at FDA. Each week, highlights of what is going on at FDA are shared to assure that new information is expeditiously made available.

The FDA has issued a final regulation that they say makes early Phase 1 clinical drug development safe and efficient by enabling a phased approach to complying with current good manufacturing practice (CGMP) statutes and FDA investigational requirements. To facilitate this new approach, the regulation exempts most Phase 1 investigational drugs from the requirements in 21 CFR part 211. FDA will continue to exercise oversight of the manufacture of these drugs under FDA’s general statutory CGMP authority and through review of investigational new drug (IND) applications. A companion guidance recommends an approach for complying with CGMP statutory requirements such as standards for the manufacturing facility and equipment, the control of components, as well as testing, stability, packaging, labeling, distribution, and record keeping. When FDA originally issued CGMP regulations for drug and biological products (21 CFR parts 210 and 211), the agency stated that the regulations applied to all types of pharmaceutical production, but explained in the preamble to the regulations that FDA was considering proposing regulations more appropriate for the manufacture of drugs used in investigational clinical trials. The reason for this is that certain requirements in part 211 are directed at the commercial manufacture of products — such as repackaging and relabeling of drug products, rotation of stock, and maintaining separate facilities for manufacturing and packaging. These types of requirements may be inappropriate to the manufacture of investigational drugs used in Phase 1 clinical trials, many of which are carried out in small-scale, academic environments, typically involving fewer than 80 subjects. The guidance, CGMP for Phase 1 Investigational Drugs, describes an approach manufacturers can use to implement manufacturing controls that are appropriate for the Phase 1 clinical trial stage of development. The approach described in this guidance reflects the fact that some manufacturing controls and the extent of manufacturing controls needed to achieve appropriate product quality differ among the various phases of clinical trials. Manufacturers will continue to submit detailed information about relevant aspects of the manufacturing process as part of the IND application. The FDA may inspect the manufacturing operation, suspend a clinical trial by placing it on “clinical hold,” or terminate the IND if there is evidence of inadequate quality control procedures that would compromise the safety of an investigational product.

To find the Guidance for Industry, CGMP for Phase 1, Investigational Drugs, visit: http://www.fda.gov/cder/guidance/GMP%20Phase1IND61608.pdf

To find Current Good Manufacturing Practice and Investigational New Drugs Intended for Use in Clinical Trials/Final rule: http://www.fda.gov/OHRMS/DOCKETS/98fr/oc07114.pdf.

For more information about our expertise in Regulatory Affairs, please contact Dr. Jules T. Mitchel or Dr. Glen Park.

In terms of electronic submissions to FDA, over the past 2 years, Target Heath prepared and submitted 2 eINDs, 1 PMA eCopy with numerous PMA eCopy supplements and 1 eCTD NDA, with numerous supplements. All submissions were accepted by FDA. We are currently preparing 2 INDs which will be submitted electronically. There are 3 main advantages of eSubmissions: 1) they are paperless and save trees; 2) they dramatically reduce the time from the end of Phase 3 to regulatory submissions; and 3), they earn money as time to market is accelerated.

For more information about Target Health or any of our software tools for clinical research, please contact Dr. Jules T. Mitchel or Ms. Joyce Hays. Our software tools are designed to partner with both CROs and Sponsors.


Streamlining desalination: Researcher Ho Bum Park holds two samples of the chlorine-tolerant desalination membrane. The one on the left is one-tenth of a micrometer thick and is made of a porous support with a thin coating of the membrane. The blue membrane is about 50 micrometers thick.
Credit: Beverly Barrett/University of Texas at Austin

A new chlorine-tolerant material may streamline desalination processes

By Jennifer Chu, July 31, 2008, MIT Technology Review – Getting access to drinking water is a daily challenge for more than one billion people in the world. Desalination may help relieve such water-stressed populations by filtering salt from abundant seawater, and there are more than 7,000 desalination plants worldwide, 250 operating in the United States alone. However, the membranes that these plants use to filter out salt tend to break down when exposed to an essential ingredient in the process: chlorine.

Now researchers at the University of Texas at Austin (UT Austin) and Virginia Polytechnic Institute have engineered a chlorine-tolerant membrane that filters out salt just as well as many commercial membranes. The researchers say that such a membrane would eliminate expensive steps in the desalination process and eventually be used to filter salt out of seawater. The results of their study appear in the most recent issue of the journal Angewandte Chemie.

The majority of desalination plants today use polyamide membranes to effectively separate salt from seawater. Since seawater harbors a variety of organisms that can form a thick film over membranes and clog the filter, plants use chlorine to disinfect incoming water before it is sent through membranes. The problem is, these membranes degrade after continuous chlorine exposure. So the desalination industry added another step, quickly dechlorinating water after it’s been treated with chlorine and before it’s run through the membrane. Once the water has been desalinated, chlorine is added again, before the water enters the drinking-water supply.

Benny Freeman, a professor of chemical engineering at UT Austin, says that a chlorine-tolerant membrane may help significantly streamline the desalination process. Freeman and James McGrath, a professor of chemistry at Virginia Polytechnic Institute, engineered a water-filtering membrane that stands up to repeated exposures of chlorine.

The new membrane is made from polysulfone, a sulfur-containing thermoplastic that is highly resistant to chlorine. Previous researchers have attempted to design chlorine-tolerant membranes using polysulfone but have been hampered because the material is extremely hydrophobic, and doesn’t easily let water through. Scientists have tried to chemically alter the polymer’s composition by adding hydrophilic, or water-attracting, compounds. However, timing is everything, and Freeman says that when researchers add such compounds after they synthesize the polymer, “eventually, you break the backbone of the polymer chain . . . to the point where it’s not useful.”

Instead, Freeman and McGrath added two hydrophilic, charged sulfonic acid groups during the polymerization process and found that they were able to synthesize a durable and reproducible polymer. They then performed a variety of experiments to gauge the material’s ability to tolerate chlorine and filter out salt, compared with commercial membranes.

First, the team carried out salt permeability tests, measuring the amount of salt passing through a membrane in a given amount of time. The less salt found in the filtered water, the better. Freeman and McGrath found that the new membrane performed just as well as many commercial membranes in filtering out water with low to medium salt content. For saltier samples comparable to seawater, the team’s membrane was slightly less permeable.

“We have materials that are competitive today with existing nano filtration and some of the brackish water membranes,” says Freeman. “We are now pushing the chemistry to get further into the seawater area, which is a significant market we’d like to access.”

The researchers also tested the polymer’s chlorine sensitivity. They found that, after exposure to concentrated solutions of chlorine for more than 35 hours, the new membrane suffered little change in composition, compared with commercial polyamide membranes, which were “eaten away by the chlorine.”

Currently, Freeman and his colleagues are further manipulating the polymer composition to try to tune various properties, in hopes of designing a more selective and chlorine-resistant membrane. They are also in talks with a leading manufacturer of desalination membranes, with the goal of bringing the new membrane to market.

“These membranes may represent a reasonable route to commercialization,” says Freeman. “If we’re successful, we’ll have the possibility of basically making these membranes on the same equipment that people use today.”

Eric Hoek, an assistant professor of civil and environmental engineering at the University of California, Los Angeles, works on engineering new desalination membranes at the California Nanosystems Institute. He says that the chlorine-tolerant membrane developed by Freeman’s team may be a promising alternative to today’s industrial counterparts.

“This work is among the most innovative and interesting research on membrane materials in the past decade,” says Hoek. “While the chlorine tolerance exhibited by these membranes is impressive, the basic separation performance is not yet where it needs to be for these materials to be touted as immediate replacements of commercial seawater membrane technology.”