Category Archives: BioEngineering

MEDIA RELEASE

IBNs Droplet Array Sheds Light on Drug-Resistant Cancer Stem Cells

Singapore, May 9, 2012 Researchers at the Institute of Bioengineering and Nanotechnology (IBN), the worlds first bioengineering and nanotechnology research institute, have developed a miniaturized biochip for investigating the effect of drugs on cancer stem cells (CSCs). Published recently in Nano Today, this new technology could boost the development of more effective cancer drugs.

In a tumor, CSCs form a small and distinct class of cancer cells that are more resistant to chemotherapy. Similar to stem cells found in human tissues, CSCs can produce and differentiate into different cell types. If CSCs are not eradicated, they can repopulate the tumor and lead to cancer recurrence. Hence, it is important for researchers to understand the efficacy of anti-cancer drugs against CSCs. However, since CSCs are so scarce they make up approximately 1% of cancer cells their study has been hampered by conventional drug screening methods, which require large sample volumes and are slow and expensive.

A team of researchers led by IBN Executive Director, Professor Jackie Y. Ying, has developed a miniaturized biological assay called the Droplet Array to perform cheaper, faster and more convenient drug screening using limited samples.

In traditional biological assays, microplates a flat plate with multiple wells in which samples are placed are commonly used, and each well requires at least 2,500 or 5,000 cells, to be present for viable analysis. By comparison, IBNs Droplet Array is a flat, rectangular glass plate on which a series of spots, each 2 millimeters in diameter, are arranged. The samples are pipetted into these tiny spots, making them appear like droplets. The plate is then coated with a layer of proprietary oil to prevent evaporation and cross contamination between the sample droplets during the rinsing process. An accompanying bench-top device to automate the rinsing process of the plate has also been developed. Being one-fifth the size of a well in a standard microplate, each spot on IBNs Droplet Array requires only 500 cells for screening. This massive reduction in sample volume not only saves money, but is also particularly advantageous for studying scarce quantities of target cells, such as CSCs.

Using the Droplet Array, the IBN researchers investigated the drug responses of CSCs extracted from breast, liver and colon cancer cells. It was found that chemotherapeutic drugs such as doxorubicin, which usually induce cell death in liver cancer cells, demonstrated poor efficacy in liver CSCs. The CSCs from the breast and colon tumors also showed much greater ability to survive the effects of anti-cancer drugs.

Animal studies were conducted to validate the findings of the Droplet Array. CSCs and non-CSCs from liver tumors were implanted into two different sets of mice at the same time. After 6 weeks, tumors were formed in the mice implanted with CSCs, whereas the mice without CSCs did not develop any tumors. Tumors extracted from the mice with CSCs also showed blood vessel formation, which confirmed the self-renewal property of these cells.

The drug resistance properties of CSCs have been widely discussed in recent years but until now, it has been challenging to quantify this correlation. Using the Droplet Array, IBN researchers have successfully demonstrated that CSCs can survive chemotherapy and drive metastasis.

Professor Jackie Y. Ying said, The Droplet Array marks a significant breakthrough in nanotechnology and lab-on-a-chip concepts, and provides an efficient platform for accelerating drug screening and development. The study of cancer stem cells, in particular, is an exciting application of this technology for both the academic and pharmaceutical industries. We hope that this finding will facilitate the development of more effective cancer drugs. We also hope to leverage on the Droplet Arrays capabilities to complement/replace animal models for drug toxicity testing, and develop new cancer diagnostics.

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:: 09, May 2012 :: IBN’S DROPLET ARRAY SHEDS LIGHT ON DRUG-RESISTANT CANCER STEM CELLS

Public release date: 30-Apr-2012 [ | E-mail | Share ]

Contact: Wileen Wong Kromhout wwkromhout@support.ucla.edu 310-206-0540 University of California - Los Angeles

If you throw a rubber balloon filled with water against a wall, it will spread out and deform on impact, while the same balloon filled with honey, which is more viscous, will deform much less. If the balloon's elastic rubber was stiffer, an even smaller change in shape would be observed.

By simply analyzing how much a balloon changes shape upon hitting a wall, you can uncover information about its physical properties.

Although cells are not simple sacks of fluid, they also contain viscous and elastic properties related to the membranes that surround them; their internal structural elements, such as organelles; and the packed DNA arrangement in their nuclei. Because variations in these properties can provide information about cells' state of activity and can be indicative of diseases such as cancer, they are important to measure.

UCLA bioengineering researchers have taken advantage of cells' physical properties to develop a new instrument that slams cells against a wall of fluid and quickly analyzes the physical response, allowing for the identification of cancer and other cell states without expensive chemical tags.

The instrument, called a deformability cytometer, was developed by UCLA biomedical engineering doctoral students Daniel Gossett and Henry Tse and assistant professor of bioengineering Dino Di Carlo. It consists of a miniaturized microfluidic chip that sequentially aligns cells so that they hit a wall of fluid at rates of thousands of cells per second. A specialized camera captures microscopic images of these cells at a rate of 140,000 pictures per second, and these images are then automatically analyzed by custom software to extract information about the cells' physical properties.

Other researchers had previously discovered that the physical properties of cells could provide useful information about cell health, but previous techniques had been confined to academic research labs because measuring the cells of interest could take hours or even days. With the deformability cytometer, the group can prepare samples and conduct an analysis of tens of thousands of cells within 10 to 30 minutes.

"Our system makes use of an approach that (U.S. Secretary of Energy) Steven Chu used to stretch DNA to, instead, stretch cells," Di Carlo said. "This required us to engineer the fluid dynamics of the system such that cells always entered the stretching flow in the same place, making use of inertial focusing technology my group has been pioneering."

With a system in place to measure the physical properties of cells at much higher rates, the bioengineers teamed up with collaborators across the UCLA campus to measure various cell populations of interest to biologists and doctors.

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When cells hit the wall: UCLA engineers put the squeeze on cells to diagnose disease

ScienceDaily (May 1, 2012) If you throw a rubber balloon filled with water against a wall, it will spread out and deform on impact, while the same balloon filled with honey, which is more viscous, will deform much less. If the balloon's elastic rubber was stiffer, an even smaller change in shape would be observed.

By simply analyzing how much a balloon changes shape upon hitting a wall, you can uncover information about its physical properties.

Although cells are not simple sacks of fluid, they also contain viscous and elastic properties related to the membranes that surround them; their internal structural elements, such as organelles; and the packed DNA arrangement in their nuclei. Because variations in these properties can provide information about cells' state of activity and can be indicative of diseases such as cancer, they are important to measure.

UCLA bioengineering researchers have taken advantage of cells' physical properties to develop a new instrument that slams cells against a wall of fluid and quickly analyzes the physical response, allowing for the identification of cancer and other cell states without expensive chemical tags.

The instrument, called a deformability cytometer, was developed by UCLA biomedical engineering doctoral students Daniel Gossett and Henry Tse and assistant professor of bioengineering Dino Di Carlo. It consists of a miniaturized microfluidic chip that sequentially aligns cells so that they hit a wall of fluid at rates of thousands of cells per second. A specialized camera captures microscopic images of these cells at a rate of 140,000 pictures per second, and these images are then automatically analyzed by custom software to extract information about the cells' physical properties.

Other researchers had previously discovered that the physical properties of cells could provide useful information about cell health, but previous techniques had been confined to academic research labs because measuring the cells of interest could take hours or even days. With the deformability cytometer, the group can prepare samples and conduct an analysis of tens of thousands of cells within 10 to 30 minutes.

"Our system makes use of an approach that (U.S. Secretary of Energy) Steven Chu used to stretch DNA to, instead, stretch cells," Di Carlo said. "This required us to engineer the fluid dynamics of the system such that cells always entered the stretching flow in the same place, making use of inertial focusing technology my group has been pioneering."

With a system in place to measure the physical properties of cells at much higher rates, the bioengineers teamed up with collaborators across the UCLA campus to measure various cell populations of interest to biologists and doctors.

Along with UCLA stem cell biologist Amander Clark, an assistant professor of of molecular, cellular and developmental biology, Di Carlo's team confirmed that stem cells that have the capability to become any tissue type stretch much less than their progeny, which are already in the process of becoming a particular tissue.

In collaboration with cytopathologist Dr. Jian Yu Rao, a professor of pathlogy and laboratory medicine at the David Geffen School of Medicine at UCLA, the team accurately detected cancer cells from pleural fluids using the high-speed deformability cytometer. Pleural fluid, which builds up around the lungs, is traditionally challenging to analyze because it contains a mixture of cell types -- including immune cells, mesothelial cells from the chest wall lining and, potentially, low concentrations of cancer cells.

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When cells hit the wall: Engineers put the squeeze on cells to diagnose disease

This news release and any accompanying images can be accessed on the web at: http://ucsdnews.ucsd.edu/pressreleases/ blinking_microbubbles_for_early_cancer_screening _take_grand_prize_at_resear/ Blinking microbubbles for early cancer screening take grand prize at Research Expo 2012

Newswise Carolyn Schutt, a Ph.D student in bioengineering at the University of California, San Diego is developing a new imaging technique that could lead to highly-sensitive light imaging deeper inside the body, improving the way we diagnose breast cancer. Schutts research, which was entered in the nanoengineering category, received the grand prize April 12 at the UC San Diego Jacob School of Engineering Research Expo 2012.

Schutt's aim is to build a bridge between optical imaging and ultrasound imaging, in order to get the benefits of both technologies: the chemical sensitivity of visible light and the tissue penetrating properties of ultrasound. Such a "smart particle contrast agent" would render biological tissue effectively transparent to light and enable highly sensitive light imaging deeper inside the body, improving the way we diagnose cancer. Conventional X-ray mammography can only show the density of tissue, indicating the presence of a mass, but cannot determine any of the biochemical differences between a benign mass and a malignant tumor.

There is a very high false positive rate with just X-ray mammography, said Schutt, who was honored with the best poster award for the Department of NanoEngineering and Jacobs School-wide Rudee Outstanding Poster Award. By being able to extract chemical information we hope to avoid unnecessary biopsies that are done on benign lesions.

For example, because of their rapid growth, cancerous tumors consume a lot of oxygen so the area around a tumor is likely to be hypoxic or depleted of oxygen. Cancer cells also require increased blood flow to fuel their growth creating a region of new blood vessel formation. The use of this technique could allow this sort of biochemical information to be determined for tumor diagnosis.

Schutts work, advised by nanoengineering Professor Sadik Esener, focuses on the use of gas-filled microbubble contrast agents that change their fluorescence intensity, or blink, only in response to focused ultrasound. A solution of these microbubbles would be injected into the body to circulate through the blood stream. When gas microbubbles encounter an ultrasound pressure wave, they contract and expand their outer surface in response to the pressure peaks and troughs. By loading the microbubble surface with a fluorescent dye that turns off when it is very close to other dye molecules the ultrasound creates a blinking signal. Initially, less than 10 percent of the bubbles produced this modulating fluorescence. Analysis of the nanostructure by super-resolution microscopy showed that most of the dye partitioned into isolated clusters, which were likely preventing the dye from blinking in response to ultrasound. Schutt was able to manipulate the bubble nanostructure by heating the bubbles to melt their outer surface and distribute the dye more evenly, and then rapidly cooling them to lock in this distributed state. This melting and quick cooling process increased the fraction of blinking microbubbles to over 50 percent, making this a more viable imaging platform.

This blinking light can then be used to build up an image of the ultrasound-scanned tissue (a suspected tumor, for example) with the sensitivity and contrast offered by optical imaging. This is a new and powerful capability that could significantly improve present diagnostics as well as image guided therapeutic capabilities. In addition to NanoEngineering, Esener is affiliated with the departments of Electrical and Computer Engineering and Computer Science and Engineering, and UC San Diego Moores Cancer Center and director of the multi-institutional NanoTumor Center.

Schutt is also active in campus outreach and leadership programs. As a Gordon Scholar, Schutt participates in the Gordon Engineering Leadership Centers engineering leadership programs, a course of study Schutt takes seriously. In her current position as outreach chair of the Bioengineering Graduate Student Society, Schutt organized the groups exhibit at the recent San Diego Festival of Science and Engineering as well as a festival-wide science challenge for K-12 students to learn and discuss key science concepts. Read our chat with Schutt about organizing the Home Run Science Challenge.

Schutt was one of more than 230 graduate students who presented at Research Expo, which was sponsored by Qualcomm, ViaSat and SAIC. Judges were impressed by the students high level of technical proficiency and their ability to communicate their ideas.

Three-time Research Expo Judge Silvia De Dea, a staff scientist at Cymer, which is a member of the Jacobs School Corporate Affiliates Program, was impressed by the entrepreneurial mindset of many of the students she met who already had some experience with the patent process, including thinking about how their technology could be eventually sold or licensed to industry. Realizing that they had that type of mindset was very interesting, said De Dea, a Jacobs School alumna who earned a masters (2004) and doctorate (2008) in chemical engineering.

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'Blinking Microbubbles' for Early Cancer Screening Take Grand Prize at Research Expo 2012

SAN DIEGO Carolyn Schutt, a Ph.D student in bioengineering at the University of California, San Diego is developing a new imaging technique that could lead to highly-sensitive light imaging deeper inside the body, improving the way we diagnose breast cancer. Schutts research, which was entered in the nanoengineering category, received the grand prize April 12 at the UC San Diego Jacobs School of Engineering Research Expo 2012.

Schutt's aim is to build a bridge between optical imaging and ultrasound imaging, in order to get the benefits of both technologies: the chemical sensitivity of visible light and the tissue penetrating properties of ultrasound. Such a "smart particle contrast agent" would render biological tissue effectively transparent to light and enable highly sensitive light imaging deeper inside the body, improving the way we diagnose cancer. Conventional X-ray mammography can only show the density of tissue, indicating the presence of a mass, but cannot determine any of the biochemical differences between a benign mass and a malignant tumor.

There is a very high false positive rate with just X-ray mammography, said Schutt, who was honored with the best poster award for the Department of NanoEngineering and Jacobs School-wide Rudee Outstanding Poster Award. By being able to extract chemical information we hope to avoid unnecessary biopsies that are done on benign lesions.

For example, because of their rapid growth, cancerous tumors consume a lot of oxygen so the area around a tumor is likely to be hypoxic or depleted of oxygen. Cancer cells also require increased blood flow to fuel their growth creating a region of new blood vessel formation. The use of this technique could allow this sort of biochemical information to be determined for tumor diagnosis.

Schutts work, advised by nanoengineering professor Sadik Esener, focuses on the use of gas-filled microbubble contrast agents that change their fluorescence intensity, or blink, only in response to focused ultrasound. A solution of these microbubbles would be injected into the body to circulate through the blood stream. When gas microbubbles encounter an ultrasound pressure wave, they contract and expand their outer surface in response to the pressure peaks and troughs. By loading the microbubble surface with a fluorescent dye that turns off when it is very close to other dye molecules the ultrasound creates a blinking signal. Initially, less than 10 percent of the bubbles produced this modulating fluorescence. Analysis of the nanostructure by super-resolution microscopy showed that most of the dye partitioned into isolated clusters, which were likely preventing the dye from blinking in response to ultrasound. Schutt was able to manipulate the bubble nanostructure by heating the bubbles to melt their outer surface and distribute the dye more evenly, and then rapidly cooling them to lock in this distributed state. This melting and quick cooling process increased the fraction of blinking microbubbles to over 50 percent, making this a more viable imaging platform.

This blinking light can then be used to build up an image of the ultrasound-scanned tissue (a suspected tumor, for example) with the sensitivity and contrast offered by optical imaging. This is a new and powerful capability that could significantly improve present diagnostics as well as image guided therapeutic capabilities. In addition to NanoEngineering, Esener is affiliated with the departments of Electrical and Computer Engineering and Computer Science and Engineering, and UC San Diego Moores Cancer Center and director of the multi-institutional NanoTumor Center.

Schutt is also active in campus outreach and leadership programs. As a Gordon Scholar, Schutt participates in the Gordon Engineering Leadership Centers engineering leadership programs, a course of study Schutt takes seriously. In her current position as outreach chair of the Bioengineering Graduate Student Society, Schutt organized the groups exhibit at the recent San Diego Festival of Science and Engineering as well as a festival-wide science challenge for K-12 students to learn and discuss key science concepts. Read our chat with Schutt about organizing the Home Run Science Challenge.

Schutt was one of more than 230 graduate students who presented at Research Expo, which was sponsored by Qualcomm, ViaSat and SAIC. Judges were impressed by the students high level of technical proficiency and their ability to communicate their ideas.

Three-time Research Expo judge Silvia De Dea, a staff scientist at Cymer, which is a member of the Jacobs School Corporate Affiliates Program, was impressed by the entrepreneurial mindset of many of the students she met who already had some experience with the patent process, including thinking about how their technology could be eventually sold or licensed to industry. Realizing that they had that type of mindset was very interesting, said De Dea, a Jacobs School alumna who earned a masters (2004) and doctorate (2008) in chemical engineering.

Judge Greg Kusinski, DeepStar director with Chevron Energy Technology Co., who serves on the Industrial Advisory Board for the Department of NanoEngineering, said the winners demonstrated a unique capacity to explain the relevance of their research. The students had the ability to present the big picture, said Kusinski. Thats why they stood out. He said that they did a great job at showing the problem they were trying to solve, steps taken during the research process and the next steps in their research.

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Cancer screening technique wins research prize

by JIM BERGAMO / KVUE News and Photojournalist MICHAEL MOORE

kvue.com

Posted on April 24, 2012 at 9:05 PM

Updated yesterday at 9:04 AM

AUSTIN -- The words surgery and bioengineering did not seem to fit together a few decades ago. On Tuesday, students at the University of Texas got a first-hand look at how the two are now the perfect fit in the field of surgical technology.

Back in the day the board game Operation was as close as any kid got to performing an operation. On Tuesday,UT pre-med studentsand those just preoccupied with curiosity, got under the hood and took da Vinci Surgical Robots for a test drive.

"To allow students to handle equipment that is for operating procedures is fantastic," said Elizabeth Coyne, a junior studying biology. "I could not pass that up."

Students took turns on the da Vinci, and then took turns asking questions from real surgeons who shared their expertise on robotic surgery.

"It enables visualization effects that I cannot traditionally achieve," said Reginald Baptiste, M.D., who is a cardiothoracic surgeon.

Students learned that da Vinci's minimally invasive surgery benefits patients because there's less pain, blood loss and fewer complications,not to mention shorter recovery times.

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UT students get hands-on opportunity with da Vinci surgical robot