Diagnostic tool: Polymer film loaded with antibodies can capture tumor cells

 The development of polymer film loaded with antibodies that can capture tumor cells shows promise as a diagnostic tool. Cancer cells that break free from a tumor and circulate through the bloodstream spread cancer to other parts of the body. But this process, called metastasis, is extremely difficult to monitor because the circulating tumor cells (CTCs) can account for as few as one in every billion blood cells.

Research led by scientists at the RIKEN Advanced Science Institute in Wako, in collaboration with colleagues at the University of California, Los Angeles, and the Institute of Chemistry at the Chinese Academy of Sciences, Beijing, has produced a polymer film that can capture specific CTCs1. With further development, the system could help doctors to diagnose an advancing cancer and assess the effectiveness of treatments.

The researchers used a small electrical voltage to help deposit a conducting polymer film of poly(3,4-ethylenedioxythiophene) (PEDOT) bearing carboxylic acid groups on to a 2-centimeter-square glass base (Fig. 1). The polymer formed nanodots, tiny bumps that measure 100 to 300 nanometers across, depending on the voltage used (1-1.4 V).

Adding a chemical linker to the film allowed it to bind a protein called streptavidin; this protein then joined to an antibody. In turn, the antibody could latch on to an antigen called epithelial cell adhesion molecule (EpCAM), which is produced by most tumor cells. In this way, the film could grab tumor cells from just a few milliliters of a blood sample.

The team tested several types of tumor cells on films with various sizes and densities of nanodots, and used a microscope to observe how well they captured the cells. The most effective film, with nanodots measuring about 230 nanometers across and containing about 8 dots per square micrometer, captured roughly 240 breast-cancer cells per square millimeter of film. In contrast, it caught fewer than 30 cervical cancer cells that do not express EpCAM, proving that the antibody used on the film is highly selective. A smooth PEDOT-carboxylic acid film with the same antibody captured only 50 or so breast cancer cells.

The film's efficiency depends on the size and spacing of the nanodots, and the presence of the capturing antibody. Since these can be easily modified, the same method could be used to make films that sense other types of cells.

The next step is to "further optimize the nanostructures of the conducting polymers and understand in more detail the cell-capturing mechanism," says RIKEN unit leader Hsiao-hua Yu. "We are also currently working on a direct electrical readout of the captured cells, without needing to use a microscope."

The corresponding author for this highlight is based at the Yu Initiative Research Unit, RIKEN Advanced Science Institute

Story Source:

The above story is reprinted from materials provided by RIKEN, via ResearchSEA.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

Jun Sekine, Shyh-Chyang Luo, Shutao Wang, Bo Zhu, Hsian-Rong Tseng, Hsiao-hua Yu. Functionalized Conducting Polymer Nanodots for Enhanced Cell Capturing: The Synergistic Effect of Capture Agents and Nanostructures. Advanced Materials, 2011; 23 (41): 4788 DOI: 10.1002/adma.201102151

Origami-inspired paper sensor could test for malaria and HIV for less than 10 cents, report chemists

 Inspired by the paper-folding art of origami, chemists at The University of Texas at Austin have developed a 3-D paper sensor that may be able to test for diseases such as malaria and HIV for less than 10 cents a pop. The sensors can be printed out on an office printer, and take less than a minute to assemble.

Such low-cost, "point-of-care" sensors could be incredibly useful in the developing world, where the resources often don't exist to pay for lab-based tests, and where, even if the money is available, the infrastructure often doesn't exist to transport biological samples to the lab.

"This is about medicine for everybody," says Richard Crooks, the Robert A. Welch Professor of Chemistry.

One-dimensional paper sensors, such as those used in pregnancy tests, are already common but have limitations. The folded, 3-D sensors, developed by Crooks and doctoral student Hong Liu, can test for more substances in a smaller surface area and provide results for more complex tests.

"Anybody can fold them up," says Crooks. "You don't need a specialist, so you could easily imagine an NGO with some volunteers folding these things up and passing them out. They're easy to produce as well, so the production could be shifted to the clientele as well. They don't need to be made in the developed world."

The results of the team's experiments with the origami Paper Analytical Device, or oPAD, were published in October in the Journal of the American Chemical Society and this week in Analytical Chemistry.

The inspiration for the sensor came when Liu read a pioneering paper by Harvard University chemist George Whitesides.

Whitesides was the first to build a three-dimensional "microfluidic" paper sensor that could test for biological targets. His sensor, however, was expensive and time-consuming to make, and was constructed in a way that limited its uses.

"They had to pattern several pieces of paper using photolithography, cut them with lasers, and then tape them together with two-sided tape," says Liu, a member of Crooks' lab. "When I read the paper, I remembered when I was a child growing up in China, and our teacher taught us origami. I realized it didn't have to be so difficult. It can be very easy. Just fold the paper, and then apply pressure."

Within a few weeks of experiments, Liu had fabricated the sensor on one simple sheet using photolithography or simply an office printer they have in the lab. Folding it over into multiple layers takes less than a minute and requires no tools or special alignment techniques. Just fingers.

Crooks says that the principles underlying the sensor, which they've successfully tested on glucose and a common protein, are related to the home pregnancy test. A hydrophobic material, such as wax or photoresist, is laid down into tiny canyons on chromatography paper. It channels the sample that's being tested -- urine, blood, or saliva, for instance -- to spots on the paper where test reagents have been embedded.

If the sample has whatever targets the sensor is designed to detect, it'll react in an easily detectable manner. It might turn a specific color, for instance, or fluoresce under a UV light. Then it can be read by eye.

"Biomarkers for all kinds of diseases already exist," says Crooks. "Basically you spot-test reagents for these markers on these paper fluidics. They're entrapped there. Then you introduce your sample. At the end you unfold this piece of paper, and if it's one color, you've got a problem, and if not, then you're probably OK."

Crooks and Liu have also engineered a way to add a simple battery to their sensor so that it can run tests that require power. Their prototype uses aluminum foil and looks for glucose in urine. Crooks estimates that including such a battery would add only a few cents to the cost of producing the sensor.

"You just pee on it and it lights up," says Crooks. "The urine has enough salt that it activates the battery. It acts as the electrolyte for the battery."

Story Source:

The above story is reprinted from materials provided by University of Texas at Austin.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

Hong Liu, Richard M. Crooks. Paper-Based Electrochemical Sensing Platform with Integral Battery and Electrochromic Read-Out. Analytical Chemistry, 2012; 84 (5): 2528 DOI: 10.1021/ac203457h

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Squeezing silicone polymers produces chemical energy, but raises doubts about implant safety

 A polymer is a mesh of chains, which slowly break over time due to the pressure from ordinary wear and tear. When a polymer is squeezed, the pressure breaks chemical bonds and produces free radicals: ions with unpaired electrons, full of untapped energy. These molecules are responsible for aging, DNA damage and cancer in the human body.

In a new study, Northwestern University scientists turned to squeezed polymers and free radicals in a search for new energy sources. They found incredible promise but also some real problems. Their report is published by the journal Angewandte Chemie.

The researchers demonstrated that radicals from compressed polymers generate significant amounts of energy that can be used to power chemical reactions in water. This energy has typically been unused but now can be harnessed when polymers are under stress in ordinary circumstances -- as in shoe soles, car tires or when compacting plastic bags.

They also discovered during the study that a silicone polymer commonly used in implants for cosmetic procedures releases a large quantity of harmful free radicals when the polymer is under only a moderate amount of pressure. These findings suggest the safety of certain polymer-based medical implants should be looked at more closely.

"We have established that polymers under stress create free radicals with overall efficiencies of up to 30 percent and shoot the radicals out into the surrounding medium where they can drive chemical reactions," said Bartosz A. Grzybowski, an author of the paper and the Kenneth Burgess Professor of Physical Chemistry and Chemical Systems Engineering. "These radicals can be useful or they can be harmful, depending on the situation."

Grzybowski and his team are the first to use this energy to drive chemical reactions by simply surrounding the compressed polymer with water containing desired reagents.

The radicals created in the polymer migrate toward the polymer/water interface where they produce hydrogen peroxide, which then can drive chemical processes.

"You can get a surprisingly large amount of chemical energy from a polymer under compression," Grzybowski said. "This energy is, in a sense, free for the taking. Under normal circumstances, the energy is virtually never retrieved from deformed polymers, which then age unproductively. But you could recharge a battery from the energy produced by walking or driving a car. And you could capture even more energy when compacting millions of plastic bags."

Grzybowski is also director of Northwestern's Non-Equilibrium Energy Research Center, which is funded by the U.S. Department of Energy.

"We are interested in new sources of chemical energy, and this energy from the simple breaking of polymers' bonds is not being used," he said. "By surrounding the polymer with a medium, such as water, we can produce environmentally friendly chemical energy. One direction we are pursuing is to use this energy to sanitize water in developing countries. This is possible because hydrogen peroxide produced by squeezed polymers kills bacteria."

The researchers confirmed that mechanical deformation -- moderate squeezing -- created free radicals in the polymers. They also determined the number of radicals produced in a polymer under pressure is approximately 1016 (10 to the 16th) radicals per cubic centimeter of polymer -- a substantial amount.

They next filled polymer tubes with water, squeezed the tubes and measured the total number of radicals that migrated into the surrounding solution. They found that nearly 80 percent of the radicals made the trip.

Grzybowski and his team demonstrated they can squeeze a polymer, such as what might be found in a shoe, tire or plastic bag, and get a mechanical-to-chemical energy conversion of up to 30 percent -- approaching the energy efficiency of a car engine.

The hydrogen peroxide produced when a polymer surrounded by water is squeezed can power a variety of chemical reactions, including fluorescence, nanoparticle synthesis and dye bleaching, the researchers showed.

To illustrate the process, they converted a Nike Air LeBron shoe into a "lightning shoe," where the air pockets in the polymeric sole are filled with a solution of a compound that lights up in the presence of radicals. After a person walked in the shoe for 30 minutes or more, enough radicals were created to generate a blue glow visible to the naked eye.

The researchers studied seven different polymers, including a number of particular public interest. Poly(dimethylsiloxane), a silicon-based material commonly used in medical implants, was one of them. In the lab experiments, the medium surrounding the polymer and the amount of pressure exerted on the material were similar to what would be found in the human body, Grzybowski pointed out.

"Our findings are somewhat worrisome since every polymeric implant in the human body experiences mechanical stresses and, as we now know, can produce harmful free radicals and liberate them into surrounding tissues, which may contribute to diseases such as cancer, stroke, myocardial infarction, diabetes and other major disorders," Grzybowski said. "With this knowledge, I am quite happy to have a metal implant in my knee, rather than a polymer implant.

"From a scientific perspective, our work proves yet again that a phenomenon can be useful or harmful depending on how we implement it," he said. "The same polymer can be a useful source of energy when outside of a human body, yet a potential risk hazard when implanted into it."

Story Source:

The above story is reprinted from materials provided by Northwestern University. The original article was written by Megan Fellman.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

H. Tarik Baytekin, Bilge Baytekin, Bartosz A. Grzybowski. Mechanoradicals Created in “Polymeric Sponges” Drive Reactions in Aqueous Media. Angewandte Chemie, 2012; DOI: 10.1002/ange.201108110

Strong Grip: Unexpected interaction between organic semiconductors

 Jülich physicists have discovered an unexpectedly strong bond between organic layers. Such structures are still puzzling scientists throughout the world. These structures form the basis for novel electronic components made from organic semiconductors that are now increasingly used in smart phones and television sets.

The results have been published in the journal Physical Review Letters.

Organic semiconductors are cheap to produce, can be flexibly shaped and are relatively insensitive to external influences. In principle, they could in future even be simply printed on plastic foils. They are already widely used as organic light-emitting diodes (OLEDs), particularly in smart phones, because they consume so little power. Nevertheless, the electronic properties of these complex materials still remain largely unknown. Researchers are particularly interested in the interfaces because component performance decisively depends on how well contacts can be created with other organic and metallic conductors. The stronger the bond, the better electrons can pass from one material to the other -- and the more power or light can be produced by solar cells or light-emitting diodes.

However, organic molecules do not usually form such strong bonds. "Scientists have assumed that organic materials only interact among themselves via weak van der Waals forces. Only in contact with certain metals do they display stronger bonding known as chemisorption," says Dr. Christian Kumpf from Forschungszentrum Jülich. "For the first time, we have been able to demonstrate such chemisorption between two organic layers, which we applied to a silver crystal by chemical vapour deposition." Such sandwich-like structures are also found in OLEDs and usually consist of several organic layers between two metallic conductors.

For the analysis, Kumpf and his colleagues made use of PTCDA, an organic semiconductor material, and copper phthalocyanine, which is frequently used as a dye. They then investigated the layers, which are only one molecule thick, using various highly specialized measuring techniques. By means of ultraviolet photoelectron spectroscopy (UPS), the researchers were able to show that a change is transferred between the organic semiconductors. They also used scanning tunnelling microscopy (STM) and low-energy electron diffraction (LEED) to demonstrate that the arrangement of the molecules is transferred to the next layer in the order of the strong bonding, almost like a photocopy.

It has been known for some time that certain metals can establish such strong interactions with an organic semiconductor. In his earlier work, Kumpf himself contributed to research in this field, even before moving to Prof. Stefan Tautz's group in Jülich in 2008. "What is new is that the charge transfer takes place between these organic materials, that was rather unexpected. These findings will undoubtedly be exploited in the development of new organic semiconductors," says Tautz, director at the Jülich Peter Grünberg Institute (PGI-3: Functional Nanostructures at Surfaces). There is, however, still a long way to go since industrial manufacturing processes and laboratory requirements are quite different; the latter being more concerned with reproducibility and precision.

Story Source:

The above story is reprinted from materials provided by Forschungszentrum Juelich, via AlphaGalileo.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

Benjamin Stadtmüller, Tomoki Sueyoshi, Georgy Kichin, Ingo Kröger, Sergey Soubatch, Ruslan Temirov, F. Tautz, Christian Kumpf. Commensurate Registry and Chemisorption at a Hetero-organic Interface. Physical Review Letters, 2012; 108 (10) DOI: 10.1103/PhysRevLett.108.106103