The Petri dish is a shallow, circular, glass or plastic dish with a loose-fitting cover over the top and sides, used for culturing bacteria and other microorganisms. The story of the Petri dish is an interesting one. Julius Richard Petri (1852-1921), a bacteriologist, worked for the master of “germ theory” in Germany in the late 1800s, Robert Koch (1843-1910). Initially, bacteria were cultured in liquid broth–a practice captured in famous images of experiments on spontaneous generation. Koch saw the advantage of growing bacteria on a solid medium instead. By spreading out mixtures of microorganisms on a solid surface, he could separate individual types in isolated colonies. With pure colonies, he could investigate the effects of each bacterium. The method allowed Koch to identify the specific organisms that cause tuberculosis, cholera, diphtheria, among many other diseases–and then to develop vaccines. At first, however, Koch used a “puddle” of gelatin on a flat piece of glass. Later, the gelatin was spread on the side of a flat bottle, accessed through a narrow opening at the end. Petri, however, realized that one could pour the gelatin in a shallow dish, and put a cover on it, making it easier to get at the bacterial cultures. Since then, of course, the Petri dish has become a staple in laboratory work–and not just in studying microbes. Koch’s work is certainly remembered (though oddly his name does not carry beyond the world of microbiologists, in the way that Pasteur’s has). However, at the same time, the name of Koch’s assistant has become a household word, though few know exactly who he was.

SyntheMed, Inc., a biomaterials company engaged in the development and commercialization of anti-adhesion and drug delivery products, announced that the Circulatory System Devices Advisory Panel of the FDA has recommended approval of REPEL-CV® Adhesion Barrier for use in pediatric patients (21 and younger) who are likely to need secondary open heart surgery. The panel also recommended the development of additional safety data as a basis for expanding the indicated use to include adult patients.

Target Health is pleased that it provided clinical trial monitoring, biostatistics, data management, medical writing, and regulatory services for the program. Target Health also prepared and submitted the PMA, including the eCopy. Target e*CRF® was used for the pivotal trial.

For more information, please contact Dr. Jules T. Mitchel. or Joyce Hays.

A team of Brown University biomedical engineers has invented a 3-D Petri dish that can grow cells in three dimensions, a method that promises to quickly and cheaply produce more realistic cells for drug development and tissue transplantation.

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Well-rounded growth. A new 3-D Petri dish allows cells to assemble themselves into bits of microtissue with natural cell-to-cell connections. (Credit: Peter Chai and Anthony Napolitano)

The technique employs a new dish – cleverly crafted from a sugary substance long used in science laboratories – that allows cells to self-assemble naturally and form “microtissues.” A description of how the 3-D dish works appears in the journal Tissue Engineering.

“It’s a new technology with a lot of promise to improve biomedical research,” said Jeffrey Morgan, a Brown professor of medical science and engineering.

Morgan conceived and created the 3-D Petri dish with a team of Brown students led by Anthony Napolitano, a Ph.D. candidate in the biomedical engineering program. Napolitano spent two years perfecting the new dish and recently won a $15,000 award from the National Collegiate Inventors and Innovators Alliance to develop the patent-pending technology into a commercially viable product.

“This technology is an inexpensive and easy-to-use alternative to current 3-D cell culture methods,” Napolitano said. “It’s the next generation.”

The technology tackles a topic of increasing interest to scientists: creating hothouse cells that look and behave more like cells grown in the human body. Since 1877, scientists have relied on the Petri dish to grow, or culture, cells. The cells stick to the bottom of the dishes and spread out as they multiply. In the body, however, cells don’t grow that way. They are surrounded by other cells in three dimensions, forming tissues such as skin, muscle, and bone. This is what happens in Morgan’s 3-D dish.

The clear, rubbery dish is the size of a silver dollar. It is made from a water-based gel made of agarose, a complex carbohydrate long used in molecular biology. This gel has a few benefits. It is porous, allowing nutrients and waste to circulate. And it is non-adhesive, so cells won’t stick to it. At the bottom of the dish sit 820 tiny recesses or wells. When cells are added to the dish –about 1 million at a time – roughly 1,000 sink to the bottom of each well and form a pile. These close quarters allow cells to self-assemble, or form natural cell-to-cell connections, a process not possible in traditional Petri dishes.

The result: microtissues consisting of hundreds of cells, even of different types. In Tissue Engineering, the Brown team describes how they combined human fibroblasts, which make connective tissue, and endothelial cells, which line the heart and blood vessels. The cells came together to form spheres and doughnut-shaped clusters. The process was quick – self-assembly took place in less than 24 hours.

“These microtissues have several potential uses,” Morgan said. “They can be used to test new cancer compounds and other drugs. And they can be transplanted into the body to regenerate tissue, such as pancreatic cells for diabetics. While there are other methods out there for making microtissues, our 3-D technology is fast, easy and inexpensive. It can make hundreds of thousands of microtissues in a single step.”

Differences in culture techniques matter in biomedicine, according to a growing body of research. Studies show sometimes dramatic differences in the shape, function and growth patterns of cells cultured in 2-D compared with cells cultured in 3-D. For example, a recent Brown study found that nerve cells grown in 3-D environments grew faster, had a more realistic shape and deployed hundreds of different genes compared to cells grown in 2-D environments.

That’s why several laboratories are pursuing 3-D cell culture methods. Brown Technology Partnerships has filed a patent application based on the technology developed in the Morgan lab and is actively pursuing licensing partners.

Napolitano was lead author of the Tissue Engineering article, and Morgan was senior author. Other members of the research team included Peter Chai, a student at The Warren Alpert Medical School of Brown University and Dylan Dean, an M.D./Ph.D. graduate student in the molecular pharmacology and physiology program.

The National Science Foundation funded the research.

Note: This story has been adapted from a news release issued by Brown University.

You’re invited to scroll down and view, ten works of art, all on silicon chips.

#1
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This sailboat, from a 1970s Texas Instrument chip, is the earliest example of chip artwork found so far.

#2
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This cheetah appeared in a Hewlett-Packard memory controller chip. This art was problematic: The cheetah’s aluminum spots flaked off, causing short circuits elsewhere on the chip.

#3
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Marvin the Martian appears on an image sensor chip used on the Mars rovers.

#4
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This image of Thor, god of thunder, appears in a Hewlett-Packard chip. It’s drawn with an unusual method: Tiny dots appear where “via” wires extend downward through the chip to connect different layers. This is the largest chip image in the Silicon Zoo.

#5
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This image of Waldo from the “Where’s Waldo” children’s book series was the first silicon artwork found by Silicon Zoo curator Michael Davidson.

#6
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A tiny train rides “tracks” that are used in charge-coupled devices to convert electrical signals into digital information.

#7
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A chip used in Digital Equipment’s MicroVax 3000 and 6200 minicomputers carries a message in Russia’s Cyrillic alphabet: “VAX–when you care enough to steal the very best.” The message was intended for technicians on the other side of the Cold War who might try to reverse-engineer the VAX designs by looking closely at the originals.

#8
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In a burst of symbolism, Intel engineers crafted an image of a shepherd looking after a two-headed ram. The real purpose of the Intel 8207 chip: a dual-port RAM (random access memory) controller.

#9
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A rendition of a Mickey Mouse watch is shown on a Mostek 5017 alarm clock chip.

#10
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Catchphrases appear in this chip’s mock fine print, including “Keep away from fire,” “Not for resale” and “No purchase necessary.”

On September 19, 2007, the Circulatory System Devices Panel will discuss, make recommendations and vote on a premarket approval application, sponsored by SyntheMed, Inc., for the REPEL-CV. REPEL-CV is a surgical adjuvant indicated for reducing the incidence, severity and extent of post-operative adhesion formation in patients undergoing cardiac surgery. Target Health is pleased to announce that it will attend the meeting on behalf of the sponsor. For this program, Target Health provided regulatory consulting, monitoring, data management, biostatistical and medical writing services. We prepared and submitted the PMA (including eCopy) and Target e*CRF® was used for the pivotal trial. The meeting is being held at the Hilton Washington DC North/Gaithersburg, Gaithersburg , MD.

For more information about Target Health, please contact Dr. Jules T. Mitchel. or Joyce Hays.

Researchers at the University of Sheffield in England, have developed a long-acting growth hormone. The new discovery could mean that children and adults with growth hormone 1) ___ will not have to have injections as often, reducing the need for daily treatments. Most hormones and 2) ___ have a short life and therefore require frequent injections as therapy. The new technology developed, means that scientists and clinicians are able to generate effective, long-acting hormones which promote growth over a minimum of ten days, after just one 3) ___. Cytokines are a subset of 4) ___ that enable communication between cells and the external environment, including the immune system. Cytokines hold huge potential for the treatment of disease due to their often fundamental roles in the development and progression of 5) ___. The research, published in the journal Nature Medicine, shows that the hormones are able to act for longer because of unique characteristics in the new 6) ___ created. Hormones normally circulate in blood attached to binding 7) ___ that prevent their clearance from the circulation and prolong their biological action. The new molecules, are able to bind to each other in a head-to-tail configuration, doubling their molecular mass in the 8) ___. This delays their absorption and elimination from the blood and therefore generates a hormone that will last for a longer period of time. This technology could bring significant benefit to patients. Children and adults with growth hormone deficiency have to give themselves daily injections and it is hoped that the new technology will reduce the number of times they have to do this to once every two weeks, or even once a month. The team is in the early stages of the drug 9) ___ process, and any drugs resulting from this research are several years away. The technology can also be applied to treat 10) ___ diseases such as multiple-sclerosis, cancer and metabolic diseases.


ANSWERS: 1) disorders; 2) cytokines; 3) injection; 4) hormones; 5) disease; 6) molecules; 7) proteins; 8) bloodstream; 9) development; 10) inflammatory

“Basal cells” are the stem cells in the nose.
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“And the nose [pause] has been cloned!” Miles Monroe (Woody Allen) Sleeper, 1973

For several years neuroscientists have been exploring the use of the stem cells found in the nose to help address injury and disease. Currently several teams of scientists are competing to develop clinical methods to help paralyzed patients.

The olfactory mucosa is one of the few sites where adults continue to grow new nerve cells from stem cells. Smell receptors can quickly regenerate after a cold or other damage. Professor Alan Mackay-Sim, deputy director of the Institute for Cell and Molecular Therapy at Griffith University, Queensland, has been studying smell and the unique properties of the cells he found in the nose for years. His team has been studying potential use of olfactory stem cells in treating Parkinson’s disease and is using stem cells from Parkinson’s sufferers to investigate the causes of Parkinson’s.

Since nasal stem cells are abundantly available in a patient’s own nose, concerns about transplant rejection are minimal, and no cultured stem cells from anyone’s embryo are needed.

According to Mackay-Sim,

Our goal is to repair the brain and spinal cord by taking small pieces of tissue from the nose and transplanting these cells back into the same person in a manner similar to a skin graft. The cells could be grown in a dish to expand their numbers or they could be genetically engineered to cause them to express therapeutic molecules. The nose is the only place where neurons, and their associated cells, are easily accessible. Nasal transplants would overcome many ethical issues associated with cell therapy, such as the use of embryonic cells. [source]

Dr. Geoffrey Raisman and his team at University College London have experimented with rats, using nasal stem cells to repair spinal injuries. Dr Carlos Lima at the Egaz Moniz Hospital in Lisbon has performed similar operations on dozens of human patients.

Neural crest stem cells are another type of embryonic stem cell that persist into adulthood in hair follicles. Maya Sieber-Blum of the Medical College of Wisconsin and Milos Grim of Charles University Prague have previously shown that follicles might provide stem cells for some types of cell replacement therapy. (Abstract of a report of their work.)

The team at Griffiths University in Queensland, Australia, recently announced results of research where they transplanted cells from the olfactory mucosa of humans, rats, and mice in to chicken embryos. They demonstrated the cells can give rise not only to nerve cells but also to heart, liver, kidney, and muscle cells. A paper on their work is to be published online this week in Developmental Dynamics. “Multipotent stem cell in adult olfactory mucosa”, Wayne Murrell et al. (Abstract here. Subscription required for full text.)

This announcement got a lot of ink, partly because it comes in the middle of a debate in Australia about the legality of embryonic stem cell research, and partly because the research was partly funded by the Catholic Archdiocese of Sydney. Naturally anything about stem cells becomes political these days.

Dr. Murrell has said he hopes the findings will help advance adult stem cell research. “It’s not that they can do more than the bone marrow or brain stem cells; it’s just that, we hope, they will be easier to work with.”

Comment

The citizens of California have committed to tax themselves $6 billion to establish a stem cell research center and sponsor stem cell research in their state, since the U.S. federal government has stopped funding research using embryonic stem cell lines.

Here is the web site of The California Institute for Regenerative Medicine.

About CIRM
The California Institute for Regenerative Medicine (“The Institute” or “CIRM”) was established in early 2005 with the passage of Proposition 71, the California Stem Cell Research and Cures Initiative. The statewide ballot measure, which provided $3 billion in funding for stem cell research at California universities and research institutions, was approved by California voters on November 2, 2004, and called for the establishment of a new state agency to make grants and provide loans for stem cell research, research facilities and other vital research opportunities. The Independent Citizens Oversight Committee (“ICOC”) is the 29-member governing board for the Institute. The ICOC members are public officials, appointed on the basis of their experience earned in California’s leading public universities, non-profit academic and research institutions, patient advocacy groups and the biotechnology industry.

79_50_0.jpgClick here for full view.

This true color mosaic of Jupiter was constructed from images taken by the narrow angle camera onboard NASA’s Cassini spacecraft starting at 5:31 Universal time on December 29, 2000, as the spacecraft neared Jupiter during its flyby of the giant planet. It is the most detailed global color portrait of Jupiter ever produced; the smallest visible features are ~ 60 km (37 miles) across. The mosaic is composed of 27 images: nine images were required to cover the entire planet in a tic-tac-toe pattern, and each of those locations was imaged in red, green, and blue to provide true color. Although Cassini’s camera can see more colors than humans can, Jupiter here looks the way that the human eye would see it.

Cassini’s camera is digital, much like today’s popular cameras, and it takes images in each color separately as different spectral filters are rotated in front of its light-sensitive detector. Over an hour was required for this portrait. Jupiter rotated during this time, so the face it presented to the camera, and the lighting on its moving clouds, were constantly changing. In order to assemble a seamless mosaic, each image was first digitally re-positioned to reflect the planet’s appearance at the instant the first exposure was taken. Then, the lighting variation across each image was removed, and the mosaic was re-illuminated by a computer-generated ‘Sun’ from a direction that allowed all imaged portions to appear in sunlight at once. The result, which was slightly contrast-enhanced to bring out subtleties in the Jupiter atmosphere, is a view that the spacecraft would have had at the same distance from the planet but ~ 80 degrees solar phase.

Everything visible on the planet is a cloud. The parallel reddish-brown and white bands, the white ovals, and the large Great Red Spot persist over many years despite the intense turbulence visible in the atmosphere. The most energetic features are the small, bright clouds to the left of the Great Red Spot and in similar locations in the northern half of the planet. These clouds grow and disappear over a few days and generate lightning. Streaks form as clouds are sheared apart by Jupiter’s intense jet streams that run parallel to the colored bands. The prominent dark band in the northern half of the planet is the location of Jupiter’s fastest jet stream, with eastward winds of 480 km (300 miles) per hour. Jupiter’s diameter is eleven times that of Earth, so the smallest storms on this mosaic are comparable in size to the largest hurricanes on Earth.

Unlike Earth, where only water condenses to form clouds, Jupiter’s clouds are made of ammonia, hydrogen sulfide, and water. The updrafts and downdrafts bring different mixtures of these substances up from below, leading to clouds at different heights. The brown and orange colors may be due to trace chemicals dredged up from deeper levels of the atmosphere, or they may be byproducts of chemical reactions driven by ultraviolet light from the Sun. Bluish areas, such as the small features just north and south of the equator, are areas of reduced cloud cover, where one can see deeper.

The Cassini-Huygens mission is a cooperative project of NASA, the European Space Agency and the Italian Space Agency. The Jet Propulsion Laboratory, a division of the California Institute of Technology in Pasadena, manages the Cassini-Huygens mission for NASA’s Office of Space Science, Washington, D.C. The imaging team consists of scientists from the US, England, France, and Germany. The imaging operations center and team lead (Dr. C. Porco) are based at the Space Science Institute in Boulder, Colo.

For more information about the Cassini-Huygens mission, visit http://saturn.jpl.nasa.gov and the Cassini imaging team home page, http://ciclops.org.

Credit: NASA/JPL/SSI
Released: November 13, 2003
Image/Caption Information

“We have not journeyed across the centuries, across the oceans, across the mountains, across the prairies, because we are made of sugar candy.”
—Winston Churchill

Cancer Can Be Detected By Scanning Surface Veins
Source: Purdue University

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Philip Low, Purdue’s Ralph C. Corley Distinguished Professor of Chemistry, discusses a new cancer detection method with graduate student Wei He (seated). Low’s research team is able to detect and count circulating tumor cells by shining a laser on surface veins. The team uses a two-photon fluorescence microscope (shown) to detect tumor cells labeled with tumor-specific fluorescent probes. (Credit: Purdue News Service photo/David Umberger)

A new technology for cancer detection that eliminates the need for drawing blood has been developed by Purdue University researchers.

Researchers from Purdue’s Cancer Center, Department of Chemistry and Weldon School of Biomedical Engineering collaborated with cancer and biotechnology experts from the Mayo Clinic to develop technology to detect tumor cells within the human body. By shining a laser on surface veins, such as those on the wrist and inside the cheek, researchers are able to reveal and count circulating tumor cells.

In addition to being less invasive, the new detection method is able to evaluate a much larger volume of blood than what can be drawn from a patient for analysis, said Philip Low, Purdue’s Ralph C. Corley Distinguished Professor of Chemistry.

“In the initial stages of cancer, there are very few circulating tumor cells – cells that indicate the spread of cancer and initiate secondary tumor formation,” Low said. “By increasing the volume of blood analyzed, we improve the sensitivity of the test and allow for earlier diagnosis. If there are two cancer cells in every 50 milliliters of blood, odds are the cells would not be found in a 10-milliliter blood sample. However, the cells would be found in the 100 milliliters of blood that flow through large veins each minute.”

Optical imaging provides high resolution and chemical specificity for cancer detection, but it usually suffers from limited penetration depth, making it hard to reach tumors inside the body, said Ji-Xin Cheng, an assistant professor of chemistry and biomedical engineering.

“In vivo detection of circulating tumor cells in surface veins provides an excellent way to overcome this problem,” Cheng said.

“Circulating tumor cells provide a benchmark for disease progression and precise monitoring of their levels could lead to personalized treatment,” Low said. “This technique allows us to quantify the amount of circulating tumor cells present, as opposed to tests that provide a ‘positive’ or ‘negative’ result.

“Through such precise monitoring, a physician could evaluate the response to chemotherapy and regularly adjust the dosage so that only the exact amount needed would be administered. This could reduce the time a patient is treated and the serious side effects that occur.”

The technique could provide doctors and patients results in a matter of minutes and save the medical industry millions of dollars in testing equipment, said Wei He, a graduate student in the Department of Chemistry and the Department of Biomedical Engineering. He worked on the project with Low and Cheng.

By directly labeling tumor cells while they are in the bloodstream, some of the costs and problems associated with testing drawn blood samples can be avoided, He said.

“One sample can require five to 10 test tubes during the course of sampling, processing and analysis such as handling, labeling and washing,” He said. “In addition, large hospitals can have more than 300 cancer patients in one day. Such a large influx can cause delays in sample processing and delays can affect the results of analysis.”

A paper detailing the technology and detection technique was published in the July 10 Proceedings of the National Academy of Sciences. In addition to Low, He and Cheng, postdoctoral researcher Haifeng Wang and Lynn C. Hartmann, a professor of oncology and associate director for education of the Mayo Clinic Cancer Center, co-authored the paper.

The technique uses a fluorescent tumor-specific probe that labels tumor cells in circulation. When hit by a laser, which scans across the diameter of the blood vessel 1,000 times per second, the tumor cells glow and become visible. The in vivo flow detection was performed on a two-photon fluorescence microscope in Cheng’s lab. The researchers compared several methods and found two-photon fluorescence provides the best signal to background ratio. The technology is able to scan every cell that is pumped through the vessel, He said.

Low’s team has developed two labeling agents that attach to different forms of cancer. One label targets ovarian, non-small lung, kidney and endometrial cancer, and the other targets prostate cancer.

These labels would be administered through an injection. The first label has already been tested in humans and has no adverse side effects and could potentially be administered weekly, He said.

Computed tomography, or CT, scans and magnetic resonance imaging, or MRI, are the current methods used to track the spread of cancer. These methods have a limited resolution, and a 1 millimeter tumor could go undetected by CT or MRI. The Purdue-developed technology can achieve single-cell resolution and can detect rare cell populations.

“Our method can detect cancer cells early in disease development and the test can be conducted frequently,” Low said. “Discovering the cancer early and knowing whether it has metastasized, or spread, greatly improves a patient’s chance for successful treatment.”

The laser penetrates to a depth of 100 microns and is able to examine shallow blood vessels near the surface of the skin. Advanced optical technology could be incorporated into the technology platform and enable the method to reach deeper vessels that handle larger volumes of blood, Cheng said.

The Purdue team continues to work with the Mayo Clinic and is planning to initiate a clinical trial to further evaluate the technique. The team also plans to develop labels for additional types of cancer and to downsize the equipment to make the technology portable.

This research was funded by an Indiana Elks Charities Grant, the Purdue Cancer Center and an Ovar’Coming Cancer Together research grant.

Note: This story has been adapted from a news release issued by Purdue University.

To find out more about Open Access, click here.

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