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Research Papers

Fabrication and Bioconjugation of Micro- and Nanoscale Structures Intended for Cancer-Specific Antigen Detection

[+] Author and Article Information
Kevin M. Klein, Gregory Ostrowicki

Computer-Aided Simulation of Reliability (CASPaR) Laboratory, George W. Woodruff Packaging School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332-0405

Andrew T. Gewirtz

School of Medicine, Emory University, Atlanta, GA 30322

Suresh K. Sitaraman

Computer-Aided Simulation of Reliability (CASPaR) Laboratory, George W. Woodruff Packaging School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332-0405suresh.sitaraman@me.gatech.edu

J. Electron. Packag 131(2), 021014 (Apr 28, 2009) (6 pages) doi:10.1115/1.3103937 History: Received December 05, 2007; Revised February 05, 2009; Published April 28, 2009

Cleanroom processes can be used for fabricating microscale and nanoscale structures, and such structures, when bioconjugated, can be used for detecting low levels of cancer-specific circulating antigens. The concentration of such circulating antigens in human serum continues to increase with cancer progression, and therefore, detection of cancer at very early stages of the disease can be facilitated by monitoring small increases in circulating antigen concentration. Therefore, fabrication and bioconjugation are the first steps in the development of bio-assays for cancer detection. In this work, microscale and nanoscale Au/Cr thin film structures have been fabricated on Si substrate using dc sputtering and electron-beam (e-beam) evaporation in combination with photo and e-beam lithography. Using the fabricated device material stack (Au/Cr/Si), we have assessed the binding affinity of Au, Cr, and Si with Protein G, and antibodies for prostate specific antigen and cancer antigen 125, an ovarian cancer-associated antigen. Based on our experiments, we see that the thin gold layer of the Au/Cr/Si samples provides increased biomaterial binding affinity, and the chromium layer has a similar, if not less, binding affinity compared with the silicon chip alone. Thus, this work demonstrates that the fabricated material stack provides an appropriate platform for antigen detection.

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Copyright © 2009 by American Society of Mechanical Engineers
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Figures

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Figure 1

Change in dynamic parameters of the nanoscale structures, coated with a monoclonal antibody, (a) before and (b) after the addition of analyte mass, due to antigen binding

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Figure 2

Fabrication steps for nanoscale and microscale device stack

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Figure 3

Example microscale structures: labyrinth and loop structures

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Figure 4

E-beam evaporated and e-beam lithography patterned nanoscale: triangular and rectangular looped, resistor-style nanoscale structures (100 nm wide leg, 30 nm thick, and 1000 nm long), (230 nm wide leg, 30 nm thick, and 1000 nm long), and (50 nm wide leg, 30 nm thick, and 300 nm long)

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Figure 5

E-beam evaporated and e-beam lithography patterned nanoscale structures

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Figure 6

Confocal images of nanoscale structures coated with Alexa Flour® labeled secondary antibody

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Figure 7

(a) Top view and (b) isometric view of flagella fragments bonded to a resistor-style nanoscale structure

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