We have tailored the nanowires/nanotubes to function as ultra-sensitive, real-time electrically-based biosensors. Our target ranges from cancer/infectious disease biomarker proteins to micro-scale cells. Specific examples include nucleocapsid protein, a biomarker for the notorious infectious disease, SARS, 1 brown tide alga, a biomarker for brown tide, 2 prostate specific antigen, a biomarker linked to cancer studies,3 and low-density lipoprotein, an important chemical for cardiovascular studies.4 In addition, we performed the ground-breaking work on selective biofunctionalization of nanowire arrays, an important step toward high-density DNA and protein chips.5 As general introduction, refer to our recent review paper in IEEE transactions on nanotechnology.6
Nanowire/nanotube biosensors have stimulated significant interest; however, the inevitable device-to-device variation in the biosensor performance remains a great challenge. We have developed an analytical method to calibrate nanowire biosensor responses that can suppress the device-to-device variation in sensing response significantly.
SARS biomarker detection utilizing nanowire biosensors functionalized with antibody mimic proteins is achieved.1 The use of antibody mimic proteins is employed for the first time in the structure of nanowire/nanotube biosensors, and is expected to cut down the cost of the assay/sensor significantly, since it can be artificially synthesized at large scale, even with engineered functions as demonstrated in our work.
Moreover, we have demonstrated complementary biosensing using In2O3 nanowire and CNT devices for the detection of prostate specific antigen.3 Specificity was gained via proper surface functionalization, including a novel approach developed to covalently attach PSA antibodies to In2O3 NW surfaces. In addition, electronic characterization revealed enhanced conduction for In2O3 nanowire devices and suppressed conduction for CNT devices upon PSA exposure, with sensitivity demonstrated down to 5 ng/ml for real-time detection in physiological buffer. The combination of n-type NWs and p-type CNT s shows great promise for the selective detection of desired biomolecules for health care and biomedical research. Furthermore, this approach can be easily applied to other protein systems through selection of the proper receptor and functionalization methods for the nanostructures. We believe this work will pave the way for nanomaterials to work as biosensor.
Chemical gating experiments performed with both nanowire and nanotube transistors revealed enhanced conductance for In2O3 nanowires and reduced conductance for carbon nanotube devices upon LDL exposure, which is interpreted as the local chemical gating of the amino groups on LDL particles.4 Our work represents a step forward toward using complementary multiple nanosensors for identifying species important for biomedical research and health care.
We have developed a novel selective functionalization of an array of In2O3 NW-based devices by electrochemically activating their surfaces and then immobilizing single-strand DNA.5 This is considered a key step for the future fabrication of large-scale biosensor arrays or chips for inexpensive multiplexed detection.
1. “Label-Free, Electrical Detection of the SARS Virus N-Protein with Nanowire Biosensors Utilizing Antibody Mimics as Capture Probes”,
F. N. Ishikawa, H. Chang, M. Curreli, H. Liao, C. Olson, P. Chen, R. Zhang, R. Roberts, R. Sun, R. Cote, M. Thompson, and C. Zhou,
ACS Nano, 5, 1219 (2009). (PDF)
2. “Rapid and Label-Free Cell Detection by Metal-Cluster-Decorated Carbon Nanotube Biosensors”,
F. N. Ishikawa, B. Stauffer, D. Caron, and C. Zhou,
Biosensors and Bioelectroncis, 24, 2967 (2009). (PDF)
3. “Complementary Detection of Prostate Specific Antigen Using In2O3 Nanowires and Carbon Nanotubes”,
C. Li, M. Curreli, H. Lin, F. N. Ishikawa, R. Datta, R. Cote, M. E. Thompson, and C. Zhou,
J. of Am. Chem. Soc. 127, 12484 - 12485 (2005). (PDF)
4. “Complementary Chemical Gating Effect of In2O3 Nanowires and Carbon Nanotubes in Response to Low-Density Lipoprotein”,
T. Tang, X. Liu, C. Li, B. Lei, D. Zhang, M. Rouhanizadeh, T. Hsiai, and C. Zhou,
Appl. Phys. Lett. 86, 103903 - 1-3 (2005). (PDF)
5. “Selective Functionalization of In2O3 Nanowire Mat Devices for Biosensing Application”,
M. Curreli, C. Li, Y. Sun, B. Lei, M. A. Gundersen, M. E. Thompson, and C. Zhou,
J. of Am. Chem. Soc. 127, 6922 - 6923 (2005). (PDF)
6. “Real-Time, Label-Free Detection of Biological Entities Using Nanowire-Based FETs”
M. Curreli, R. Zhang, F. N. Ishikawa, H. Chang, R. J. Cote, C. Zhou, and M. Thompson
IEEE Transactions on Nanotechnology, 7, 651 (2008). (invited review paper, PDF)