Medical Device Daily National Editor
Here's a look some interesting basic science research reports issued recently:
• Researchers at the Stanford University School of Medicine (Stanford, California) say they have developed a technique for locating and tracking those cells of the body that naturally hunt down and fight defective and diseased cells.
Use of these disease-fighting "killer" cells has been attempted, but researchers have been unable to monitor them after introduction to the body or get a complete picture of their location and operation.
Senior author of this research report, Sanjiv Gambhir, MD, PhD, director of the Stanford Molecular Imaging Program, described the two-step strategy for understanding how and where these cells might work: first, the therapeutic cells were modified to express a unique reporter gene shared by no other cells in the body; second, an imaging agent that is trapped only in cells expressing the reporter gene is injected into the patient.
Each time the imaging agent was used, the researchers obtained an up-to-date map showing the cells' locations.
Gambhir's team used the technique in a middle-aged man with an aggressive brain tumor (a glioblastoma) in a clinical trial of cell-based therapy at City of Hope (Los Angeles), saying that similar strategies will work to monitor cell-based therapies for other disorders.
"The cells were actually good at finding the tumor," said Gambhir, who pointed out that the same technique could be used to follow other immune cells or eventually stem cells throughout the body.
The researchers said that these repeated "snapshots" of the location and survival of such cells could help clinicians assess the disease-fighting performance of such cells over time, as well as for researchers trying to design more effective cell-based therapies.
"This has never before been done in a human," said Gambhir. "Until now, we've been shooting blind – never knowing why failed therapies didn't work. Did the cells die? Did they not get where we wanted them to go? Now we can repeatedly monitor them throughout their lifetime."
Gambhir, a professor of radiology and a member of Stanford's Cancer Center, collaborated in the research with researchers at City of Hope and at University of California Los Angeles.
The study was reported online Nov. 18 in Nature Clinical Practice Oncology.
• Microscopy goes to the "movies" ... and adds a dimension to 3-D.
The Physical Biology Center for Ultrafast Science and Technology of the California Institute of Technology (Caltech; Pasadena) reported development of a technique, billed as "4-D" electron microscopy, providing for the first time real-time, real-space visualization of fleeting changes in the structure and shape of matter barely a billionth of a meter in size. The researchers compared their breakthrough to the initial development of moving pictures.
A patent on the framework of this approach was granted to Caltech in 2006, and the recent work was directed by Ahmed Zewail, the Linus Pauling Professor of Chemistry, professor of physics at Caltech, and winner of the 1999 Nobel Prize in Chemistry.
The "movies" obtained with the technique – of atomic changes in materials of gold and graphite – are featured in a paper appearing in the Nov. 21 issue of the journal Science.
The method is an advance over electron microscopy which can image the static structure of objects with a resolution better than a billionth of a meter in length. An electron microscope generate a stream of individual electrons that scatter off objects to produce an image.
Zewail and colleagues say they have added the fourth dimension of time into electron microscopy via ultrafast "single-electron" imaging. The resulting image produced by each electron represents a femtosecond "still." Like the frames in a film, these sequential images can be assembled into a digital movie at the atomic scale.
"With this 4-D imaging technique, atomic-scale motions, which lead to structural, morphological, and nanomechanical phenomena, can now be visualized directly and hopefully understood," Zewail said.
His team is expanding the research to biological imaging within cells in collaboration with Grant Jensen, an associate professor of biology at Caltech. The 4-D microscope is being used to image the components of cells, such as proteins and ribosomes, producing images of a stained rat cell and, more recently, of a protein crystal and cell in vitreous water.
"The goal is to enhance the structural resolution in the images of these biomaterials by taking single-pulse snapshots before they move or deteriorate, and to follow their dynamics in real time," Zewail said.
• Two researchers have developed a method for fabricating electronics that increases the range in which they can be stretched (as much as 140%), allowing circuits to be subjected to extreme twisting.
This compares to standard electronic components that are flat and unbendable because silicon is brittle and inflexible. Bend or stretch them in any significant way and they break and become unusable.
The new bendable electronics may find important uses in medical sensors and other electronics used for human monitoring, according to the research partnership of Yonggang Huang, a professor of civil and environmental and mechanical engineering at Northwestern University (Evanston, Illinois) and John Rogers, professor of materials science and engineering at the University of Illinois (Urbana-Champaign).
The work builds on previous research by the pair – Huang focused on theory, Rogers focused on experimental design. In 2005, they developed a stretchable form of single-crystal silicon that can be stretched in one direction without altering its electrical properties; those results published by the journal Science in 2006. Earlier this year they made stretchable integrated circuits, work also published in Science.
Next, the researchers developed a technology that allowed circuits to be placed on a curved surface. This technology uses an array of circuit elements about 100 micrometers square that were connected by metal "pop-up bridges." The circuit elements were so small that when placed on a curved surface, they didn't bend, but these elements were connected by metal wires that popped up when bent or stretched.
Huang and Rogers took these pop-up bridges and made them into an "S" shape, which, in addition to bending and stretching, have enough "give" that they can be twisted as well. "For a lot of applications related to the human body – like placing a sensor on the body – an electronic device needs not only to bend and stretch but also to twist," said Huang. "So we improved our pop-up technology to accommodate this."
Their research is published online by the Proceedings of the National Academy of Sciences.