Doctoral course: Chemical and biomechanical X-ray Vision
Kontinkangas campus, Aapistie 5A
Teacher: Professor Jeffrey Anker, Clemson University.
Class 1: Simulating pH indicator dye sensors + demonstration: Monday 14.11. at 10.15-13 am (lecture room: H1091)
Class 2: Immunoassays and the Langmuir Isotherm + demonstration: Tuesday 15.11. at 12-14 pm (lecture room: P117)
Scientific Seminar: Chemical and biomechanical X-ray Vision: Tuesday 15.11. at 15-16 (lecture room: H1091)
Although implanted medical devices have been a “miracle of modern medicine,” improving patient quality of life and extending life expectancy, complication from non-union and infection are often devastating. We are developing sensors to measure the local biochemical and mechanical environment on implants both to detect clinical complications at earlier stages when treatments are less invasive, and to elucidate the underlying pathophysiology preclinically to guide methods to better address the problems. The challenge is to deliver such sensors and non-invasively read their signals through tissue. Our approach is to attach passive sensors to the orthopedic implant surface prior to implantation and read chemical and mechanical signals using optical and X-ray sensing. This talk will discuss three techniques to see molecules and forces:
1) High spatial resolution, chemical imaging of medical implant surfaces can be achieved by combining a focused X-ray beam with an optical readout: The implant surface is coated with a layer of X-ray scintillators that generate red or near infrared light when irradiated with an X-ray beam. The scintillators are in turn coated with indicator dyes with an optical absorption spectrum that modulates the luminescence spectrum in an analyte-dependent manner. The light then passes through the tissue and skin where its spectrum indicates the local chemical concentration at the implant surface. The focused X-ray beam is scanned across the implant surface to generate a chemical image point by point, with a spatial resolution defined by the X-ray beam width and chemical sensitivity provided by the optical indicators. We use this X-ray excited luminescence chemical imaging (XELCI) to image pH changes during infection on trauma plates and intramedullary rods; additionally, the approach can generally measure absorption or fluorescence for imaging oxygen, drug release, silver dissolution, mechanical strain (using photoelastic effect), lateral flow assays, and nanophosphor contrast agents.
2) Projection X-ray imaging (plain radiography) can make chemical and mechanical measurements by using a transducer on the implant surface to convert the chemical or mechanical signal into motion of a radiopaque dial or fluid. For example, polyacrylic acid-based hydrogels display pH-dependent swelling. The pH can thus be determined from the extent of hydrogel swelling by measuring the position of a radiopaque indicator pin embedded in the hydrogel. We also developed mechanical pin and hydraulic fluid-level sensor to amplify and display mechanical strain/bending of orthopedic implants for monitoring bone fracture healing. This was applied to tibial fracture, intertrochanteric (femur) fractures fixed with sliding hip screws, and cervical spine fusions. These sensors augment standard radiographs of tissue, bony anatomy, and hardware by also indicating local chemical concentrations and mechanical strain.
3) To address the Covid-19 pandemic, we started developing a simple point-of-care immunoassay that counts single molecules using a combination of buoyant and magnetic (BAM) beads. The “two factor identification” of molecules and opposing buoyant and magnetic forces dramatically improves specificity, while the buoyant mixing improves sensitivity. Analysis is done using a simple, inexpensive and portable camera, cuvette and magnet setup.
Overall, these techniques provide new abilities to see molecules and study biomechanics to detect, monitor, and study pathologies.
Jeffrey Anker is a College of Science Dean’s Distinguished Professor of Chemistry and Bioengineering at Clemson University. He obtained his BS degree in applied physics at Yale University in 1998 and his doctorate at The University of Michigan in 2005, working with Professor Raoul Kopelman. From 2005-2008, Dr. Anker was an NIH National Science Research Award (NSRA) postdoctoral research fellow at Northwestern University under the guidance of Professor Richard Van Duyne. He joined the Clemson faculty in August 2008. Current research focuses on developing "smart" implanted medical devices with sensors to detect implant infection and bone healing, as well as imaging and spectroscopy using magnetic, plasmonic, buoyant, and X-ray excited micro- and nano-sensors. He is on a Fulbright Scholar sabbatical at Tampere University through Dec 2022, with Prof. Jonathan Massera as host and Prof. Laeticia Petit as co-host.