"Super-resolution optical microscopy has opened a new window into the nanoscopic world," said Ji-Xin Cheng, an associate professor of biomedical engineering and chemistry at Purdue University.

Conventional optical microscopes can resolve objects no smaller than about 300 nanometers, or billionths of a meter, a restriction known as the "diffraction limit," which is defined as half the width of the wavelength of light being used to view the specimen. However, researchers want to view molecules such as proteins and lipids, as well as synthetic nanostructures like nanotubes, which are a few nanometers in diameter.

Such a capability could bring advances in a diverse range of disciplines, from medicine to nanoelectronics, Cheng said.

"The diffraction limit represents the fundamental limit of optical imaging resolution," Cheng said. "Stefan Hell at the Max Planck Institute and others have developed super-resolution imaging methods that require fluorescent labels. Here, we demonstrate a new scheme for breaking the diffraction limit in optical imaging of non-fluorescent species. Because it is label-free, the signal is directly from the object so that we can learn more about the nanostructure."

Findings are detailed in a research paper that appeared online Sunday (April 28) in the journal Nature Photonics.

The imaging system, called saturated transient absorption microscopy,or STAM,uses a trio of laser beams, including a doughnut-shaped laser beam that selectively illuminates some molecules but not others. Electrons in the atoms of illuminated molecules are kicked temporarily into a higher energy level and are said to be excited, while the others remain in their "ground state." Images are generated using a laser called a probe to compare the contrast between the excited and ground-state molecules.

The researchers demonstrated the technique, taking images of graphite "nanoplatelets" about 100 nanometers wide.

"It's a proof of concept and has great potential for the study of nanomaterials, both natural and synthetic," Cheng said.

The doughnut-shaped laser excitation technique, invented by researcher Stefan Hell, makes it possible to focus on yet smaller objects. Researchers hope to improve the imaging system to see objects about 10 nanometers in diameter, or about 30 times smaller than possible using conventional optical microscopes.

"We are not there yet, but a few schemes can be applied to further increase the resolution of our system," Cheng said.

The paper was co-authored by biomedical engineering doctoral student Pu Wang; research scientist Mikhail N. Slipchenko; mechanical engineering doctoral student James Mitchell; Chen Yang, an assistant professor of physical chemistry at Purdue; Eric O. Potma, an associate professor of chemistry at the University of California, Irvine; Xianfan Xu, Purdue's James J. and Carol L. Shuttleworth Professor of Mechanical Engineering; and Cheng.

Future research may include work to use lasers with shorter wavelengths of light. Because the wavelengths are shorter, the doughnut hole is smaller, possibly allowing researchers to focus on smaller objects.

The research is funded by the National Institutes of Health, National Science Foundation and the Defense Advanced Research Projects Agency.

Fall 2012 Senior Design Projects included:

• A device that is able to quantitatively define and monitor the progression of peripheral neuropathy (PN) by evaluating changes in skeletal muscle electrical activity, sweat gland function, and muscle tension during ankle reflex.*
• A prosthetic for patients with Proximal Femoral Focal Deficiency (PFFD). This prosthetic has a gear box that is used to give the user a 90 degree bending motion at an artificial knee joint. This will allow users better mobility and the ability to participate in everyday activities. †
• A companion device to an electric wheelchair utilizing an automated feedback system to regulate an external temperature being applied to the surface of the user. The combined functions of this device will provide comfort for the user and can help maintain continuous body temperature for quadriplegics.
• Hospital software application that can provide physicians and nurses with an assessment of the likelihood that heart failure patients will be readmitted if discharged based upon an analysis of the patient’s diagnosis and compliance.
• A novel electro-magnetic pumping system that provides pulsatile blood flow to congestive heart failure patients. This design can be implanted through the rib cage making the surgery less invasive.
• A low-cost, innovative chemical approach using an infant’s urine to diagnose iron deficiency. This design uses an iron specific indicator to bind the iron in the urine and create a visible color output that will be used to diagnose the infant’s iron level.  (Thanks to Abbott Laboratories for sponsoring this project and mentoring the students.)
• A walker for the elderly that reduces the risk of falls by monitoring heart rate and detecting obstacles in the user’s path. This device is also equipped to alert proper authorities in the event a fall occurs.
• A method of detecting mild to moderate traumatic brain injury (TBI) in order to prevent further injuries that may result from high risk behaviors. This design is based on the presence of protein S100b in the blood.
• A device that is able to provide physicians with a visual feedback system for heart pacemaker lead placement.
• An endotracheal tube design that causes less physical trauma and allows patients to verbally communicate while undergoing mechanical ventilation.
• A waterproof device that a swimmer would wear on their forearms that consists of an accelerometer and a gyroscope to calculate the orientation of their hand-arm position.  Through an audio tone the device will signal to the swimmer when their arm is not in an optimal orientation.
• A hand prosthetic device that would allow a person who has lost a portion of their fingers to sew.

*Fall 2012 Senior Design Best Project Award Winner (tie). Team members were Megan Kochert, Andrea Lawrence, Thomas McNamara, and Jennifer Waite. The project also won the NCIIA E-Team Stage 1 Competition.

†Fall 2012 Senior Design Best Project Award Winner (tie). This project was housed in ME and was one of the School's first ME/BME collaboration teams. Team members were Sajed Dosenba (ME), Ted Kramer (ME), Alexandra Guerra (BME), James Vandewalle (ME), and Benjamin Zakhary (BME). This project also won 2nd place in ME's Malott Innovation Award Competition.

Spring 2013 Senior Design Projects included:

• A spinal cage made from a metal that will degrade while bone fusion is occurring so that normal bone replaces the degraded metal. This design will result in the patient having no residual metal left in the body once the vertebrae have been fused.‡
• A procedural method of determining the concentration profile of a drug in skin using Stimulated Raman Scattering (SRS) microscopy to assess concentrations of molecules within thin layers of tissue without using molecular tags.
• A fetal heart-rate monitor that is low-cost, shockproof, and waterproof. It uses audio feedback to monitor the heart rate and provide visual and audible signals to the user. This device will enhance prenatal care in developing countries.
• A colorectal cancer screening management website was developed for medical clinics. This program is able to estimate a patient’s risk for colorectal cancer and will improve the efficacy of colorectal cancer treatment by enabling preventative care.
• A reduced size, lightweight knee brace that is strong enough to handle the wear and tear of use by a football player.
• A spring loaded suture, which allows for dynamic movement of the adduction muscles to allow for vocalization in patients with vocal fold paralysis (VFP). This design will improve breathing and eating, while retaining the patient’s ability to speak.

‡ Spring 2013 Senior Design Best Project Award Winner. Team members were Timothy Druyos, Paull Gossett, Emily McCuen, Robert Wilson.

Thanks to Weldon School faculty and staff members J. Paul Robinson, Ann Rundell, Marcia Pool, and Allison Sieving for advising the senior design teams. Thanks also goes to all the faculty members and clinical mentors who supported the teams in their senior design projects.

The 2012-2013 Haselby Outstanding Biomedical Engineering Senior Award winners are Alex Guerra and Johnny Zhang.

The Haselby Award was established by Ken and Carla Haselby. Ken received his BSME from Purdue in 1964 and his MD from the IUPUI School of Medicine in 1971. 

C. W. Peak and Kyle Richmond received the The Estus H. and Vashti L. Magoon Award for Excellence in Teaching. The Magoon Awards are given to outstanding teaching assistants in memory of the Magoons who have influenced the lives of many engineering educators early in the their careers through this award. C. W. has been a teaching assistant for the BME sophomore and junior professional development courses and is working on his master's degree in biomedical engineering in Gudrun Schmidt’s lab. Kyle Richmond has been a teaching assistant for the BME bioinstrumentation and biotransport laboratories and is working on a non-thesis master’s degree in electrical and computer engineering.

Andrew Koivuniemi received the Outstanding Research Award. This award goes to students who have demonstrated excellence and leadership in research through publications, participation in professional organizations, and willingness to mentor others.

Becca Scott received the Outstanding Service Scholarship which is presented to engineering graduate students who have provided outstanding service to the graduate student community, the School, the College, and/or the University.