The goal of this project is to develop an attachment for a scanning probe microscope that enables high throughput, apertureless, near field infrared microscopy (ANSIM). The development of this instrument will enable sensing applications that require the characterization of extremely small regions of complex biological materials on surfaces. The proposed near field instrument will be able to perform IR absorption spectroscopy at less than 100nm lateral spatial resolution. The ANSIM attachment will be designed to be small and portable, so that replicas of this attachment may become a practical add-on to other atomic force microscopes (AFMs). The instrument development program has three principal elements. First, infrared (IR) quantum cascade laser arrays will be assembled with the optics for guiding the IR laser light into and out of the microscope. Second, multi-channel detection and signal processing modules will be built and integrated with a common, commercial instrument. Third, improved designs of the sharp metal tip used in an apertureless near-field scanning infrared microscopes will be tested and optimized. IR spectroscopic chemical imaging of manmade polymeric surfaces at 100nm lateral resolution using apertureless near field microscopy has already been demonstrated in preliminary work. The goal of this exploratory proposal is to determine whether useful information can be acquired for imaging biological molecules, and whether technology that would be readily used by other scientists can be developed. The test measurements will concentrate on imaging peptide layers and their secondary structure, primarily using IR active amide bands. This would be the first time IR near field microscopy has been applied to peptide and protein analysis, and would represent a significant step forward in biochemical imaging using scanning probe microscopy. Polyglutamine (PG) and its aggregates have been chosen for demonstration studies because 1) PG has a relatively simple IR spectrum related to its secondary structure and 2) PG structures have been implicated in diseases associated with the deposition of insoluble aggregations of proteins, known as fibrils, in various human organs. To treat or to prevent such diseases, improved ability to observe the formation and the deposition of such insoluble aggregates is required; IR near field microscopy could have considerable impact in this area.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21EB003101-01
Application #
6711539
Study Section
Special Emphasis Panel (ZRG1-BBCB (50))
Program Officer
Zhang, Yantian
Project Start
2004-04-01
Project End
2005-03-31
Budget Start
2004-04-01
Budget End
2005-03-31
Support Year
1
Fiscal Year
2004
Total Cost
$134,096
Indirect Cost
Name
University of Pittsburgh
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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