Update
Charlene Crabb
20th Anniversary
A
dense tangle of neem
trees and gnarled bushes en-
velopes Tank 610, which, ex-
cept for a square hole of several inches
cut into its stainless steel side, looks
eerily intact for a piece of equipment
that, 20 years ago this month, was the
epicenter of the world’s worst in-
dustrial disaster — the release of
40 metric tons of methyl iso-
cyanate from a Union Carbide
Corp. pesticide manufacturing fa-
cility in Bhopal, India.
No one really knows how
many people died after inhaling
the chemicals that were spewn
from the 40-ft × 8-ft cylindrical
storage vessel on the night of
Dec. 2–3, 1984. A report released
by the Indian government last
May notes a “conservative esti- The 1984 incident in Bhopal involved a chemical explosion from Tank 610. being released into the air each
mate” of 2,500 immediate human
fatalities. In 1997, Indian officials tabu-
lated a death toll of 15,000 people,
most of whom died of chemical gas-re-
lated aftereffects, such as tuberculosis
and respiratory problems. Moreover,
hundreds of thousands of people may
have been injured.
The death and destruction in central
India served as a “wake-up call unlike
any other,” says Dorothy Kellogg, se-
nior director of Security and Operations
at the American Chemistry Council
(ACC; Arlington, VA; www.american-
chemistry.com). Industry, governments
and the public worldwide were jolted
into a greater awareness of chemical
hazards, and the corrective actions tak-
en in the wake of Bhopal ripple through
industry to this very day.
Nevertheless, process safety is still
plagued by significant weaknesses. The
U.S. currently has no sure way to assess
whether the myriad of activities designed
to improve chemical safety is actually
doing so. Opportunities to learn from in-
cidents go largely unheeded. And reac-
tive hazards remain unrecognized.
“Thankfully, we haven’t had any-
6 www.cepmagazine.org December 2004
Learning from Bhopal
thing approaching the terrible tragedy
of Bhopal,” says Gerald Poje of the
U.S. Chemical Safety and Hazard
Investigation Board (CSB;
Washington, DC; www.csb.gov). “But
there are a tremendous number of wor-
rying signs on the horizon.”
Safety in action
The specter of Bhopal catalyzed a
raft of voluntary programs and legisla-
tion aimed at prevention, training, pre-
paredness and response, which are now
integral parts of the process safety
landscape. Industry was the first to re-
act. Within four months of the tragedy,
the American Institute of Chemical
Engineers (AIChE; New York, NY;
www.aiche.org) established its Center
for Chemical Process Safety (CCPS;
New York; www.aiche.org/ccps), an
information and training clearinghouse
for process safety. In 1985, the ACC,
then known as the Chemical
Manufacturers Association, mandated
its members to adopt a program called
Community Awareness and
Emergency Response, or CAER,
which required companies to develop
emergency response plans in coopera-
tion with local emergency responders.
In 1987, the Canadian chemical indus-
try launched Responsible Care, the eth-
ic of continual improvement in health
and safety practices. Adopted by the
ACC in 1988, the program is now em-
braced by 47 countries.
CEP
Governments followed industry’s
lead by creating or amending legisla-
tion to better protect people and the
environment. In 1986, Congress
passed the Emergency Planning and
Community Right to Know Act
(EPCRA). Modeled after CAER,
EPCRA beefed up the responsi-
bilities of industry to inform
neighboring communities of
chemical hazards, as well as to
coordinate and plan emergency
response procedures both on
and off site. It also required cer-
tain facilities to annually report
the release of certain toxic
chemicals.
The first such compilation in
1988 indicated that some 4 bil-
lion lb of toxic chemicals were
year. That finding triggered
amendments to the Clean Air Act
(CAA) in 1990, such as the Process
Safety Management (PSM) standard,
which was promulgated by the
Occupational Safety and Health
Administration (OSHA; Washington,
DC; www. osha.gov) in 1992, and the
Accidental Release Prevention: Risk
Management Program (RMP), which
was promulgated by the Environmental
Protection Agency (EPA; Washington,
DC; www.epa.gov) in 1999. The CAA
amendments also authorized the cre-
ation of the CSB, an independent feder-
al agency that investigates major chem-
ical incidents to determine their root
causes.
Educational institutes are also plac-
ing more emphasis on process safety.
Many universities now include a
process safety course in the core cur-
riculum of their chemical engineering
programs — something virtually un-
heard of 20 years ago. Engineering un-
dergraduates at some schools can spe-
cialize in safety by opting for elective
courses in related areas, such as design
safety or fire protection. Graduate stu-
dents are conducting research on safe- experts want to change. One problem chemical production and use.
ty-related topics, such as runaway reac- with this yardstick, from an optimistic The Mary Kay O’Connor Process
tions or fires and explosions. point of view, is that it could soon be Safety Center at Texas A&M Univ.
This mounting awareness appears obsolete. “If we keep going the way (MKOCPSC; College Station;
to be paying off. Responsible Care we’re going, in not so many years, we http://process-safety.tamu.edu), along
companies in the U.S. succeeded in could be at zero fatalities,” says Scott with experts from industry, govern-
halving their rate of occupational in- Berger, director of CCPS. “At that ment, education and non-governmental
jury and illnesses since 1990, while ef- point, we won’t have any way to mea- organizations, attempted to devise such
fecting a 35% decrease in the number sure our progress.” methodologies for analyzing several
of reportable process safety incidents A more fundamental flaw lies in the existing federal databases. In 2001, the
since 1995. According to OSHA, the limitations of fatality, incident and in- MKOCPSC used the techniques to es-
number of fatal or catastrophic inci- jury statistics — the raw numbers fail tablish what it hoped would be a base-
dents requiring agency inspections to account for industry trends. Does the line for future annual comparisons.
also appears to be trending down — drop in fatalities this year, for example, Unfortunately, the development of
only one fatality has been recorded so reflect an improved safety performance these methods stopped there. The
far in 2004. or a sluggish economy with fewer peo- National Chemical Safety Program, as
ple in the workforce and lower chemi- the effort is known, has been unable to
Monitoring progress cal production? A more rational way to secure funding for subsequent analyses.
But gauging performance in process track the status of chemical industry Sam Mannan, director of the MKOCP-
safety merely in terms of fatalities and safety is to tie the incidents, injuries SC still hopes the project will be re-
incidents is something process safety and fatalities data to information about vived. “After all,” he says, “it’s scan-
The UUC facility permanently ceased operation in the days
BATTLING OVER BHOPAL after the gas leak, but chemicals left on site have never been
f increased awareness of process safety can be considered a
I silver lining to the cloud of deadly gas that enveloped the streets
of Bhopal 20 years ago, it is a bittersweet one. A darker legacy of
cleaned up (photo). Studies have found carcinogens, such as
chlorobenzenes, carbon tetrachloride and chloroform, in water
the disaster continues to unfold in the hospitals and medical clin- from hand-pump wells in communities surrounding the plant.
ics dotting the city and in courtrooms in both India and the U.S. More than 20,000 people live in the areas where the contaminat-
Every day at least 5,000 gas-leak survivors line up for free ed wells are located. The Indian Supreme Court directed the
treatment at more than two dozen Bhopal medical facilities. state government in May to supply clean drinking water to the
Many of the victims complain of debilitating breathlessness, residents. Construction of a pipeline that will bring 900,000 liters
aching joints and psychological disorders. Tuberculosis and res- of water a day from a nearby reservoir to the affected neighbor-
piratory infections plague those people with lungs particularly hoods is expected to begin by this month.
ravaged by the gas. Others suffer from early-onset cataracts and Last July, the U.S. Dept. of Justice rejected India’s latest re-
recurring infections of the eye, another organ highly vulnerable to quest to extradite Anderson, who has long since retired. A
methyl isocyanate. Many young women, who breathed the gas Bhopal court ruled last year that the former UCC chief should
as toddlers, have irregular menstrual cy- face criminal charges of culpable homi-
cles now. And growth retardation has cide in connection with the gas tragedy.
been reported in adolescent boys who But the U.S. government refused the re-
were in utero at the time of the leak. In ad- quest on the technical grounds that the
dition, Bhopal doctors expect that gas-re- charges against Anderson had not been
lated cancers will begin appearing in the properly framed in India, which requires
gas-effected population within five years. the accused to be present in court to hear
Compensating the victims for their suf- a judge read out the charges. Anderson
fering and loss is still the subject of ongo- briefly visited Bhopal just after the inci-
ing courtroom battles. In 1989, after four dent, but has never returned.
years of legal maneuvering, and in what News of the returned extradition request
many consider to be a legal and financial came a day after the Indian Supreme
coup, the Union Carbide Corp. (UCC) Court ordered the government to distrib-
reached a settlement with the Indian Supreme Court and paid ute $330 million in compensation directly to the victims. The
$470 million in reparations. Appeals began almost immediately, amount is the remainder of the original $470 million settlement
including continued attempts to extradite Warren Anderson, then that the government has not distributed, plus accrued interest.
chairman and CEO of UCC, to India on criminal charges. A num- However, grassroots citizen groups claim that the 1989 settle-
ber of other related lawsuits have also been filed. ment, which was based on early estimates of 3,000 deaths and
The latest chapter in the legal proceeding played out this 105,000 injuries, is insufficient compensation. Indian officials esti-
summer. In late June, the Indian Ministry of Chemicals and mated in 1997 that 578,000 people have been injured and more
Fertilizers, along with the Madhya Pradesh state government than 15,000 people have died due to gas-related illnesses.
where Bhopal is located, informed the U.S. Second Circuit Court Meanwhile, officials of the Madhya Pradesh state government,
of Appeals that both governments have “no objection” to UCC who are mostly members of a Hindu political party, are bucking
being directed to clean up the abandoned pesticide factory. The to have all 56 wards in Bhopal declared gas-effected and thus el-
official statement is the latest volley in a class-action lawsuit filed igible to receive part of the settlement. Currently, 36 wards are
in 1999 in New York that seeks clean up of the abandoned pesti- considered to have been touched by the gas cloud. About 45%
cide plant, decontamination of groundwater and compensation of the population in those communities is Muslim. The popula-
for resultant health problems. tions of the 20 other wards are largely Hindu.

CEP December 2004 www.cepmagazine.org 7

Update
dalous to not know where we are in
terms of process safety.”
Undoubtedly, Bhopal and other
headline-grabbing events have pro-
pelled improvements in chemical
process safety. But there is concern that
industry is not learning as much as it
should from incidents that occur on a
smaller scale and closer to home.
In the U.S. especially, liability is-
sues hinder companies from sharing
insights that could be gained from sys-
tem emergencies or failures. To en-
courage more extramural communica-
tion, some safety specialists support
the idea of allowing companies to ne-
gotiate for fewer citations or lower
fines if they agree to disseminate infor-
mation that would help other firms
prevent similar mishaps.
Even within organizations, valu-
able safety lessons slip through the
cracks. According to Poje, CSB inves-
tigators find that major incidents are
often preceded by similar, less detri-
mental events and “a failure to learn
lessons from them.” Indeed, incidents
generally receive intense scrutiny only
if they cause injury, death or substan-
tial property loss. But “incidents”
range from catastrophic to near-miss-
es, or even just upset conditions.
Further, the possibility that a system
upset may escalate to disaster can
merely depend on happenstance. For
example, the release of a toxic gas
could result in numerous fatalities or
none at all, depending, quite literally,
on which way the wind blows.
“We need to get away from a cul-
ture where we just investigate or react
when people are killed or injured or
when there’s major property loss, and
develop a culture where we investigate
near-misses and ask what could have
happened if…” Mannan says.
Reactive chemical hazards is anoth-
er process safety issue that needs atten-
tion and action, experts say. The CSB
put the spotlight on such hazards two
years ago with its analysis of 167 inci-
dents that occurred in the U.S. from
1980 to 2001 and involved runaway
chemical reactions. The accidents
caused 108 fatalities, as well as mil-
lions of dollars in property damage.
CSB found that more than 90% of
8 www.cepmagazine.org December 2004
the events involved hazards that are al-
ready recognized and documented in
literature. In addition, more than half
of the accidents involved chemicals
that are currently exempt from process
safety regulation because they pose
relatively low potential hazards. “But,
put them into a reactor, add tempera-
ture and pressure, and you’re creating
what could become a very dangerous
bomb,” says Poje.
Then again, a reactor may not even
be necessary. Uncontrolled reactions
can, and do, occur anywhere incom-
patible chemicals are inadvertently
mixed. The deadly cloud of chemicals
unleashed in Bhopal resulted after wa-
ter somehow entered the methyl iso-
cyanate storage tank.
Based on its two-year study, CSB
made 18 recommendations to reduce
the number of serious uncontrolled
chemical reactions, explosions, fires
or toxic gas releases caused by reac-
tive hazards. For example, the board
wants OSHA to broaden the PSM
standard to include individual chemi-
cals and combinations thereof that can
undergo hazardous reactions under
specific process conditions. PSM cur-
rently applies to only 137 listed chem-
icals, plus a class of flammable sub-
stances. But only 38 of the combined
total of these chemicals are considered
“highly reactive.”
To date, neither OSHA nor EPA
has placed CSB’s recommendations
on their respective regulatory agendas.
One ray of hope emerged last March
when the two agencies, together with
seven chemical industry organiza-
tions, formed an alliance to provide
businesses with information about
chemical reactive hazards. Several
technical experts from business and
government have also formed a
roundtable aimed at brainstorming
methods to better manage reactive
chemical hazards. “However, no one
has explained how any of these soft
pathways will solve the problem,”
Poje says. “We’re going to be dogged
in pursuing the leverage to
get the situation fixed.” CEP
Charlene Crabb is a science writer
based in Paris, France.
CEP
PROCESS TECHNOLOGY
Pervaporation Membranes Get Tough
The separation of aromatics from
aliphatic hydrocarbons is posing chal-
lenges to the chemical and petrochemi-
cal industries, especially as legislative
pressure to remove benzene from
aliphatics or from gasoline becomes in-
creasingly stringent. Pervaporation,
which separates compounds based on
sorption and diffusion properties, could
offer technical and economical benefits
over conventional processes such as
liquid extraction, extractive distillation
and azeotropic distillation, which are
highly complex and have high invest-
ment and operating costs. But, to date,
the commercial use of pervaporation
membranes has been limited because
the process requires long-term expo-
sure to organic liquids at high tempera-
tures, which makes the small pores
chemically and mechanically unstable.
PolyAn, Inc. (Berlin, Germany;
www.poly-an.com), in collaboration
with GKSS Research Center GmbH
(Teltow, Germany; www.gkss.de), has
developed the first pervaporation
membrane that selectively, yet cost-ef-
fectively, removes benzene from non-
aromatic compounds. The membrane
was designed using molecular surface
engineering (MSE) technology, which
covalently immobilizes an ultra-thin
polymer film onto a microporous
membrane. “The polymer is function-
alized to achieve the desired separa-
tion, and serves to improve membrane
stability,” says PolyAn business man-
ager Heike Matuschewski. He adds
that MSE can create these pervapora-
tion membranes at the commercial
scale in a reproducible manner.
The membrane is being used in a
pervaporation system that is integrated
with an extractive distillation process at
an undisclosed plant in Gelsenkirchen,
Germany, to purify benzene. Feed,
flowing at 15–20 L/h, enters the perva-
poration unit at 80–100°C and a few
bars of pressure. Benzene is vaporized
on the other side of the membrane at a
pressure of about 100 mbars. The ben-
zene-rich permeate stream is returned to
the extraction column. The purity of the
aliphatic stream is greater than 99%.
A Physiological Approach to Pipeline Integrity Brinker is developing its Platelet technology to provide
Brinker Technology Ltd. (Aberdeen, Scotland; leak location and sealing capability in pipelines ranging
www.brinker-technology.com), the recent Univ. of from 3/8-in. dia. to 48-in. dia. The firm is also exploring the
Aberdeen spin-out firm, has achieved the first commercial use of Platelet technology to provide emergency response
implementation of its Platelet technology for sealing and lo- service to leaks on large-bore-diameter pipelines, for locat-
cating leaks in pipelines. Working closely with BP (London, ing leaks on hydraulic or chemical injection lines, and for
U.K.; www.bp.com) and Aker Kvaerner (Lysaker, Norway; extending the lifetime of certain pipelines.
www.akerkvaerner.com), Brinker suc-
cessfully sealed a leak on a subsea water
injection pipeline on BP’s Foinaven
field. “The procedure from the start of
the offshore operation to successful seal
took less than 24 hours and allowed BP
to quickly increase water injection from
141,000 to 154,000 bbl/d with an imme-
diate effect on reservoir production,”
says Sandy Meldrum of BP. Platelet
technology has not only the capability
to seal a leak, but also to identify the po-
sition of the leak, she says.
Platelets are free-floating, polymer-
based devices that are injected into the
pipeline at very low concentrations us-
ing existing infrastructure, and are de-
livered to the site of rupture via fluid
flow — much like the way platelets in
blood, flow to injured tissues to initiate
coagulation. They range in size from
200 mm to sub-mm and come in a va-
riety of different shapes, depending on
the design issues involved. “Each re-
leased platelet has a certain statistical
probability of being entrained into a
leak, which depends on flow condi-
tions and leak geometry,” explains Ian
McEwan Brinker’s technical director
and Platelet technology inventor. The
Brinker team uses tools such as com-
putational fluid dynamics and flow-
loop testing to evaluate this probabili-
ty. Once at the site of rupture, the
Platelet is held firmly in position by
the pressure differential acting across
it, thereby plugging the leak. Excess
Platelets can be removed using a
downstream strainer system.
“The composition of the material
depends on the density of the medium,
strength requirements, ambient condi-
tions and chemical compatibility with
the medium or product,” says McEwan.
Fabrication is generally achieved by in-
jection molding with a RFID tag or ra-
dioisotopes embedded inside the
Platelet to reveal its position, and thus
the location of the leak.
www.cepmagazine.org or Circle No.119

CEP December 2004 www.cepmagazine.org 9

Update

Whole-Cell Approach to Dipeptide
Production Cuts Costs
Kyowa Hakko Kogyo Co.
(Tokyo, Japan; www.kyowa.co.jp)
has developed a new fermentation-
based route to amino acid dimers or
dipeptides. Production costs are sub-
stantially lower than those utilizing
conventional methods, which are
known chemical or enzymatic
processes (the latter of which are
based on the reverse reaction of pep-
tide hydrolases). “These competitive
routes to dipeptides require complex
protection and de-protection steps to
control and advance the reaction, re-
sulting in low yields, high costs and
many byproducts,” says Akio Ozaki,
Kyowa’s general manger of R&D.
The key to Kyowa’s process is
amino acid ligase, an enzyme pro-
duced by Bacillus subtilis, that directly
combines amino acids without requir-
ing protection and de-protection steps.
The reaction proceeds stoichiometri-
cally at theoretical yields of 100%,
while the actual yield depends on the
rates of reaction for corresponding
amino acids. The firm will make use of
its process by 2006 to begin commer-
cial production of alanyl glutamine, a
dipeptide made of L-alanine and L-
glutamine. “We expect the alanyl glut-
amine market to grow to about
100–200 ton/yr within a few years af-
ter the launch, and will increase pro-
duction to several hundred tons per
year in the future,” says Ozaki.
The gene coding the ligase was iso-
lated and engineered into E. coli, in
which it is overexpressed. The mi-
croorganisms are fermented at 30°C, 1
atm and neutral pH in the presence of
L-alanine and L-glutamine, which are
converted to alanyl glutamine by the
naturally occurring enzyme. Despite
their success at the laboratory scale,
the scientists had to overcome major
obstacles before scaleup of the reaction
could be considered. “Because dipep-
tides are good nutrients for cell
growth, the microorganisms tend to
degrade them very quickly,” explains
Ozaki. “We developed a strain that

ENABLING ABSOLUTE PARTICLE SIZING

W yatt Technology, Inc. (Santa Barbara, CA; www.wy-
att.com) is formally launching a particle-sizing sys-
tem that integrates two of its most advanced macromolecu-
lar characterization instruments — the Eclipse field flow
fractionation (FFF) device and the DAWN multi-angle light
scattering (MALS) detection system — to achieve absolute
particle sizing for samples containing submicron particles
without the need for device calibration or sizing standards,
as is required when using conventional particle separation
systems, such as hydrodynamic chromatography (HDC).
“Because there is no interaction with a stationary phase and
low shear forces, the method is less likely to degrade the
sample,” notes Christoph Johann, managing director of
Wyatt Technology Europe GmbH.
Although the DAWN enhanced optical system (EOS) is
the only MALS detector capable of simultaneous determi-
nation of the average radius and molar mass of the sample
in the detector cell, a separation is needed to provide distrib-
ution information. This is the role of the FFF system to
which the DAWN is coupled.
As with classic chromatography, sample components
elute at given retention times that are proportional to the hy-
drodynamic diameter of the molecules. During operation, a
sample is injected into the channel formed by an upper, im-
permeable plate that is bolted to a lower, porous plate made
of a frit material. An ultrafiltration membrane, with a typical
size barrier of 10 kiloDalton (kD), covers the bottom plate
to prevent the sample from penetrating the channel. As the
sample flows through the bottom frit, it creates a frictional
force that is perpendicular to the direction of transport. This
force drives the sample towards the channel bottom (often
called the accumulation wall) at a different velocity from the
flow at the center of the channel. Diffusion associated with
Brownian motion acts as a counterforce that drives the mol-
ecules away from the bottom wall.
When the system reaches a state of equilibrium, mole-
cules of every size find a specific average height above the
accumulation wall. Smaller particles, which have higher dif-
fusion rates, reach an equilibrium position furthest away
from the accumulation wall, which is on the order of a few
micrometers. The parabolic profile of flow along the chan-
nel translates the particles’ positions in height into different
elution times from the channel. The smaller particles elute
more quickly than larger particles, due to their higher diffu-
sion coefficients. “This is exactly the opposite of what oc-
curs during a size-exclusion or gel permeation chromato-
graphic (SEC/GPC) separation, in which the large
molecules elute first,” Johann points out. “The resolution of
FFF is very high, so that the sample fractions eluting at
every given time interval from the FFF channel are nearly
monodisperse — that is, they contain molecules or particles
of one size only,” he adds. Size differences between subse-
quent slices of 1 nm can be resolved reliably.
The resolution of the Eclipse-DAWN system can only
be matched by either ultracentrifugation (UC) or electron
microscopy (EM). For instance, with the Eclipse-DAWN
system, one can analyze a fraction offline, a capability
that is not possible with alternative methods. But, he
quickly points out that in terms of cost, UC and EM are
far more expensive than the Eclipse-DAWN system,
which ranges from $100,000 to $150,000 and also has a
lower cost of ownership.
The Eclipse-DAWN system has been tested extensively
for the characterization of cancer and other vaccines and to
improve the beer fermentation process. One major brewery
claims that the technology provides detailed information
about the structure of polysaccharides produced by the yeast,
which is linked to the quality of beer, as reflected in its shelf
life. Stressed yeast creates a different structure, which causes
the beer to haze before the “best-used-before” date.

10 www.cepmagazine.org December 2004 CEP

grows normally, yet has a low dipeptide degradation rate.”
Secondly, the reaction requires adensine triphosphate (ATP)
— “an expensive energy source to add as a raw material,”
Ozaki notes. But, Kyowa engineered a process that regener-
ates ATP from ADP within cells, so the need for ATP has no
impact on production costs.
Both chemical and fermentation-based dipetide produc-
tion technologies require amino acids as starting materials, A sugar on the surface of a mouse cell (right) modified with an azide
which generally cost $10–$100/kg. Kyowa would not com- group, and a probe comprising a phosphine attached to a peptide (Flag,
ment on the actual production costs of dipeptidies via its left) join in the Staudinger ligation. Fluorescence of a Flag antibody reveals
technology, but said that they are “much less” than those for a successful ligation.
conventional approaches, which are estimated to cost ap- tions with cell-surface sugars, while sparing the cells any
proximately 10 times as much as the amino-acid raw materi- upset to their metabolism.
al investment. While the firm’s initial focus is on the devel- Key to the success of Bertozzi’s technique, which is
opment of alanyl glutamine production, the new process can based on the the Staudinger ligation reaction, is what she
be used to manufacture many other dipeptides. “We have al- calls bio-orthogonality. Chemical reactions artificially in-
ready confirmed the formation of more than 60 dipeptides on duced on the cell surface must be highly selective and able to
the laboratory scale,” Ozaki says. take place in the cell’s warm, watery physiological environ-
ment, but have no harmful biological effects. The Staudinger
R&D UPDATE ligation, which takes place between an azide and a phos-
Corrosion Theory Supports Spreading of Unstable Pits phine, was modified by Bertozzi to ensure the ligation prod-
Research into the process of pitting corrosion in stainless (R&D Update continues on p. 13)
steel, conducted by scientists at the Univ. of Virginia
(Charlottesville; www.virginia.edu) and the Berlin-based
Fritz-Haber Institute of the Max Planck Society (www.fhi-
berlin.mpg.de), is challenging the accepted wisdom of how
rust develops and may reveal new ways to combatting a phe-
nomenon that is estimated to cost U.S. business and industry
the equivalent of 3%/yr of the U.S. gross national product
(GNP). According to the St. Louis Federal Reserve Bank,
this figure was $11.5 trillion in July 2004.
The researchers conducted a series of experiments to track
the development of tiny pits of corrosion on sheets of stain-
less steel in response to changes in the temperature or concen-
tration of salt in solutions. The effects of the experiments, ob-
served under a microscope, were not what other scientists
have theorized — i.e., that individual pits stabilize and grow
independently. Instead, they saw a critical point at which
things changed dramatically. “Even slight changes in the con-
ditions can greatly increase the likelihood of the sudden onset
of pitting corrosion as a cooperative critical phenomenon re-
sulting from interactions among metastable pits,” says Jack
Hudson, professor of chemical engineering at the Univ. of
Virginia. This causes an explosive phase of frenzied activity
spurred by a chemical interaction among numerous pits.
The research suggests that corrosion can be controlled by
factors that minimize the interaction of the small pits.
Possible approaches include changing the metal alloys used
or cleaning the reaction products from the metal’s surface.

Engineering Cell Surfaces

Researchers at the Dept. of Energy’s Lawrence
Berkeley National Laboratory (CA; www.lbl.gov), led by
Carolyn Bertozzi, also a professor of chemistry at the Univ.
of California at Berkeley (www.berkeley.edu), have for the
first time, enabled markers to be attached to cells via reac-
www.cepmagazine.org or Circle No.120

CEP December 2004 www.cepmagazine.org 11

 Update
HONING THE ART OF CREATING NANOMETER-SCALE PATTERNS
The ability to rapidly pattern and
write conductive polymers has been
identified as one of the target areas for
fabrication of organic electronic and
optoelectronic devices. This is coupled
with an increased demand for minia-
turization of conductive polymers to
the nanometer-size scale has resulted
in state-of-the-art techniques such as
dip-pen nanolithography (DPN),
which uses atomic-force-mi-
croscopy (AFM) probes mea-
suring 20–30 nm at the tip to
prepare conductive polymer
lines down to 290-nm width at
writing speeds as high as 0.8
µm/s. The probe tip is coated
with an ink that consists of ioni-
cally charged, conducting poly- Figure 1. This diagram shows the difference between traditional
mers that flow from the tip onto dip-pen nanolithography using liquid ink (left) and thermal dip-pen
the oppositely charged substrate nanolithography
Naval Research Laboratory.
surface and are applied as long
as the dip pen remains in contact
with the substrate. To date, however,
DPN has been limited by an inability
to turn the ink flow on and off once
contact is made.
Researchers from the Georgia
Institute of Technology (GIT; Atlanta
www.gatech.edu) and the Naval
Research Laboratory (NRL;
Washington, DC; www.nrl.navy.mil)
have developed a technique, dubbed
thermal dip-pen nanolithography
(tDPN) that overcomes this obstacle
by using meltable solid inks, such as
wax or solder, and AFM microcan-
tilever probes with built-in heaters
(microcantilever heaters) that can be cross-linking with the swollen film; the cross-linking reac- These speeds are attributed to the ab-
activated and deactivated at will
(Figure 1).
The microcantilevers are fabricated
out of crystalline silicon doped with
atomic impurities that allow electricity
to flow through them and heat up
“much like the resistive elements of an
electric stove,” explains William King,
professor of mechanical engineering at
GIT. At one end, the device is plugged
into an electrical socket; the wires get
smaller and smaller until they reach
the heater in the microcantilever.
“Electrical current is programmed
to turn on and off within billionths of
12 www.cepmagazine.org December 2004
a second, causing the temperature of
the heater to rise and fall in about a
millionth of a second,” explains
King. The dip pen only deposits ma-
terial on the substrate when heat is
activated, providing control over the
deposition process.
During experimentation, the re-
searchers used octadecylphosphonic
acid (OPA), which melts at about
Cold Cantilever Hot Cantilever
Ink
Substrate Substrate
using ink materials that melt (right). Image courtesy of
Conductive Atomic Force
Microscopy (ATM) Probe
Moving Direction
Substrate
Precursor Polymer Conductive Polymer
Figure 2. During electrochemical oxidative nanolithography, SPL technique for nanowriting of con-
a conductive electrode is brought in contact with a film sub-
strate bearing a potential that initiates solid-state oxidative
tion ensues to produce a conductive polymer.
100°C, as their ink, producing lines
about 95 nm wide at speeds of 1
nm/µs. They are optimizing the
process to make features as small as
10 nm, which are “well beyond the
limits of conventional semiconduc-
tor-patterning processes that depend
on light projected through a litho-
graphic mask,” says King. Using or-
ganic materials, the researchers hope
to produce a working semiconductor
prototype by the end of this year.
Within the scope of this work, the
CEP
rapid, direct writing of a conductive
polymer at the <100-nm scale on
glass has been achieved via a novel
scanning probe-based lithography
(SPL) technique called electrochemi-
cal oxidative nanolithography (EON;
Figure 2). Developed by Univ. of
Connecticut chemistry professor
Gregory Sotzing, and Los Alamos
National Laboratories’ chemist
Manuel Marquez, it combines
electrochemical AFM with sol-
id-state oxidative cross-linking
(SOC), a process during which
a polymer in the solid swollen
state is converted to a cross-
linked polymer with a conduc-
tivity of approximately one or-
der of magnitude higher than
that reported for conductive
polymers that are electrochemi-
cally cross-linked.
A conductive AFM tip is
brought in contact with a film sub-
strate bearing a potential that is high
enough to initiate SOC with the
swollen film; the cross-linking reac-
tion ensues to produce a conductive
polymer. Conductive polymer lines
with widths of 120 nm, 170 nm and
240 nm were patterned into a precur-
sor plastic at writing speeds of 60, 30,
and 15 µm/s, respectively, using a po-
tential of 1.4 V. “To our knowledge,
these writing speeds are 1,500 times
faster than the only other reported
ducting polymers,” says Sotzing.
sence of material transfer from tip to
substrate, and because neither nucle-
ation nor growth is required to form
conductive polymer, as in DPN, ac-
cording to the researchers. The soft-
ened polymer is drawn toward the tip
by the attractive electrostatic forces
between the charged tip and the pre-
cursor polymer film.
A limiting factor in EON is the
movement of polymer chains for
cross-linkable molecules to find each
other. This is currently controlled by
plasticizing the polymer to make the
chains more mobile.
REGULATORY UPDATE (NOI) to be covered. Under the CGP, permit coverage starts at
Permit Change Clarifies Eligibility vs. Accountability the time of discharge authorization. In the case of the CGP, this

O n Sept. 16, the U.S. Environmental Protection Agency

(EPA; Washington. DC; www.epa.gov) proposed modifi-
cations of permit conditions covered under the National
Pollutant Discharge Elimination System (NPDES) general per-
mit for storm water discharges from construction activities.
The general permit is available for use where the EPA is the
NPDES permitting authority, as opposed to those states where
the state issues NPDES permits. Coverage under the
Construction General Permit (CGP) authorizes the discharge of
storm water from construction activities consistent with the
terms of the permit.
Primarily, the proposed revisions clarify that permit
noncompliance only applies to sites with permit coverage.
In addition, the proposed revision, if adopted, will correct
a typographical error in the permit and a corresponding er-
ror in the fact sheet.
As written, the CGP suggests that construction site opera-
tors may be liable for permit noncompliance, even when the
operator is not covered, or not yet covered, by that permit. This
might occur before the operator submits a notice of intent
is typically after a seven-day waiting period subsequent to an
operator’s submission of an NOI to EPA. As established in the
CGP, to obtain permit coverage, operators must meet certain
eligibility criteria (e.g., development of a site-specific storm
water pollution prevention plan).
However, failure of the operator to act to become eligible
for permit coverage does not constitute permit noncompliance.
Rather an operator who fails to meet all applicable eligibility
provisions is not authorized for permit coverage. Thus, failure
to apply for a permit may indicate other types of noncompli-
ance (e.g., violation of CWA section 402 for discharging with-
out a permit, or violation of 40 CFR 122.21(c)(1) for failure to
submit a permit application at least 90 days before the date on
which construction is to commence). As an alternative, any op-
erator may apply for coverage under an individual permit, as
opposed to seeking to use the CGP. For more information, see
the Federal Register, 09/16/2004, pp. 55,818–55,821.
Regulatory Update is prepared by William A. Shirley, P.E., J.D.,
a chemical engineer and attorney in private practice in St. Louis, MO;
Phone: (888) OSHA-LAW; E-mail: envtllaw@charter.net.

(R&D Update continued from p. 11)

uct formed from these compounds is
stable under physiological conditions.
To get the azide-half of the reac-
tion to show up on the cell surfaces, a
precursor containing the azide group
is diffused into the cells. This precur-
sor is a sialic-acid-containing form of
oligosaccharide that is naturally pro-
duced by the stomach cells of mice
and displayed on their surfaces.
The azide-containing precursor
was injected into the abdomen of live
mice, after which it was absorbed by
the cells in the spleen and other or-
gans. Examination of the spleen cells
revealed an abundance of the cell-sur-
face azides. The other reactant, phos-
phine, can be attached to the markers.
To confirm the success of the
Staudinger ligation, the scientists used
a peptide marker that could be identi-
fied by a fluorescing antibody.
Work demonstrating the
Staudinger ligation in mice has diag-
nostic possibilities, says Bertozzi.
“Molecules detectable by magnetic
resonance imaging could be injected
into organs to seek out cells with cer-
tain glycosylation patterns (e.g., those
of cell-surface sugars characteristic of
cancerous cells).”
www.cepmagazine.org or Circle No.121

CEP December 2004 www.cepmagazine.org 13