Nano/Micro Devices for Diagnostics and Treatment

Fabricating Medical Devices at the Micro and Nano Scale

In the Micro and Nano Integrated Biosystem Laboratory (MINIBio) in the Department of Bioengineering, Siyang Zheng and his students use micro- and nanofabrication technology to create devices to study fundamental biological processes, to improve diagnosis of diseases, and to treat patients in more convenient and economical ways through the use of miniaturized devices and systems.

Zheng’s research group is a dialog across several disciplines, with students drawn from electrical engineering, materials science, and both mechanical and chemical engineering. His collaborators include chemists, physicists, and medical researchers in pharmacology and pathology. This multidisciplinary approach is the key to solving biomedical problems, he believes.

Zheng’s own education has crossed fields that don’t normally intersect. After graduating from Tsinghua University, Beijing, with a major in biological sciences, he spent two years studying biochemistry and molecular biology at Penn State before switching to electrical engineering and earning a Master’s degree. He followed this with a year in industry, working at Lucent Technologies in the field of signal processing and communication software programming. He then took a Ph.D. in electrical engineering from Caltech, where he also did his postdoctoral study. At Caltech, Zheng discovered that he had a knack for making biomedical devices that drew on his varied interests. He came to Penn State and opened his MINIBio lab in early 2009.

A blood-counting device for NASA

Lab-on-a-chip and other miniaturized medical devices serve several useful functions that have drawn intense interest in the biomedical field. The hope is to replace large pieces of diagnostic equipment that are generally only available at centralized labs and hospitals with devices that are portable and inexpensive for use in doctors’ offices or at home. A second area of intense research is in developing implantable, biocompatible, miniaturized devices for sensing, diagnosing, and treating illness inside the body.

Zheng’s first successful device, developed as a graduate student at Caltech with his adviser Yu Chong Tai’s research group, is a cell phone sized blood counter for diagnosing bacterial infections. The device divides and counts white and red blood cells in a small blood sample, using a microfluidic chip to pump the blood, and fluorescence detection to analyze the blood cells. Another device uses a 1cm x 1cm chip to measure electrical impedance to count blood cells. The devices were conceived as a simple method for astronauts to monitor their medical condition on long space flights.

In a new project, Zheng’s Ph.D. student, Tim Yin-Ting Yeh, is developing a unique device for biomolecule transport and separation in collaboration with Donghai Wang in Mechanical Engineering and Tom Baker in Entomology. “We are trying to use bottom-up synthesis methods to create an array of parallel nanochannels inside microchannels,” Zheng remarks. “So we could, for example, try to concentrate and separate volatile organic compounds (VOCs) from breath analysis, or separate peptides, or make a sensor to do ionic sensing.” If the device is successful, the nanochannel would be useful in DNA separation and sequencing. By making the channel somewhat larger, it would be possible to do protein separation.

Although Zheng’s lab is equipped with some fabrication tools, he relies on the wider range of tools available in the user facilities of the Penn State Nanofab. The Nanofab is part of the National Nanotechnology Infrastructure Network (NNIN), which is a National Science Foundation-sponsored nationwide network of user facilities to enable rapid advancements in science, engineering, and technology at the nanoscale. “All of my Ph.D. students use the Nanofab. The people there give us a lot of help,” he says.

Microfilters for cancer detection

Most cancer deaths occur when cancer cells break loose from the original tumor site and migrate through the blood or lymph system to form a new metastatic tumor elsewhere in the body. Starting from his early years at Caltech, Zheng’s recent work has involved creating filters to capture those circulating cells in cancer patients and portable devices to analyze the cells on-chip.

“Circulating cancer cells are rare,” says Zheng, “maybe one in a billion blood cells. If we could keep captured cells alive and culture them, this would be a breakthrough.” To capture these rare cells, Zheng used microfabrication techniques to design filters with the correct size, geometry and density of pores that will let smaller normal blood cells pass through while capturing larger cancer cells.