The thrust of this research proposal is to advance fundamental understanding of a relatively new and innovative label-free optical biosensor technology based on porous silicon microcavities.
The specific aims are designed to investigate key parameters in the fabrication of an affinity sensor for the detecting Candida. Phage display scFv antibody probes that target cell wall surface antigen will serve as the receptor. A goal will be to discover whether these probes can function in an immobilized format to distinguish between the Candida blastoconidia (noninvasive) and filamentous (pathogenic) forms. Foundation knowledge will be gained on understanding the dependence of the porous silicon microstructure (porosity, pore morphology) and surface chemistry on biomoiecular infiltration and sensor sensitivity. A key aim will be to determine the sensor can detect Candida antigen at levels typically expressed in a primary skin infection. A mouse model of primary Candida infection will be utilized as a source of antigen from skin. To accomplish these goals a reporter assay will be used to quantify the activity of the immobilized scFv probes relative to a solution control. Initial work will be done using devices in a single-probe chip format. The silicon microfabrication facility at the Rochester Institute of Technology will be leveraged to investigate the process steps required to fabricate an arrayed-probe chip format so multiple targets could be assayed simultaneously. Access to this facility will also enable studies to elucidate fundamental insight into the material science challenges of sensor fabrication. The proposed research will generate knowledge that is broadly extensible to the detection of other pathogenic organisms and proteomic conjugates. Essential skills will be acquired that comprise a critical component of the training process to become a successful independent investigator in biomedical sciences. ? ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Mentored Quantitative Research Career Development Award (K25)
Project #
5K25AI060884-02
Application #
7062417
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Duncan, Rory A
Project Start
2005-06-01
Project End
2010-04-30
Budget Start
2006-05-01
Budget End
2007-04-30
Support Year
2
Fiscal Year
2006
Total Cost
$121,090
Indirect Cost
Name
University of Rochester
Department
Dermatology
Type
Schools of Dentistry
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627
Mortensen, Luke J; Faulknor, Renea; Ravichandran, Supriya et al. (2015) UVB Dependence of Quantum Dot Reactive Oxygen Species Generation in Common Skin Cell Models. J Biomed Nanotechnol 11:1644-52
Mortensen, Luke J; Jatana, Samreen; Gelein, Robert et al. (2013) Quantification of quantum dot murine skin penetration with UVR barrier impairment. Nanotoxicology 7:1386-98
Mortensen, Luke J; Ravichandran, Supriya; Delouise, Lisa A (2013) The impact of UVB exposure and differentiation state of primary keratinocytes on their interaction with quantum dots. Nanotoxicology 7:1244-54
Ravichandran, Supriya; Mortensen, Luke J; DeLouise, Lisa A (2011) Quantification of human skin barrier function and susceptibility to quantum dot skin penetration. Nanotoxicology 5:675-86
Chandrasekaran, Siddarth; Giang, Ut-Binh T; King, Michael R et al. (2011) Microenvironment induced spheroid to sheeting transition of immortalized human keratinocytes (HaCaT) cultured in microbubbles formed in polydimethylsiloxane. Biomaterials 32:7159-68
Bonanno, Lisa M; Kwong, Tai C; DeLouise, Lisa A (2010) Label-free porous silicon immunosensor for broad detection of opiates in a blind clinical study and results comparison to commercial analytical chemistry techniques. Anal Chem 82:9711-8
Bonanno, Lisa M; Delouise, Lisa A (2010) Integration of a Chemical-Responsive Hydrogel into a Porous Silicon Photonic Sensor for Visual Colorimetric Readout. Adv Funct Mater 20:573-578
Bonanno, Lisa M; Delouise, Lisa A (2010) Tunable detection sensitivity of opiates in urine via a label-free porous silicon competitive inhibition immunosensor. Anal Chem 82:714-22
Mortensen, Luke J; Oberdorster, Gunter; Pentland, Alice P et al. (2008) In vivo skin penetration of quantum dot nanoparticles in the murine model: the effect of UVR. Nano Lett 8:2779-87
Furbert, Patrick; Lu, Caiyan; Winograd, Nicholas et al. (2008) Label-free optical detection of peptide synthesis on a porous silicon scaffold/sensor. Langmuir 24:2908-15

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