Citation Classic
Clinical Chemistry 61:4 664–665 (2015)
Nanoelectronics Aiming at Cancer Gengfeng Zheng1*
Featured Article: Zheng GF, Patolsky F, Cui Y, Wang WU, Lieber CM. Multiplexed electrical detection of cancer markers with nanowire sensor arrays. Nat Biotechnol 2005;23:1294 –301.2 There are ⬎200 types of cancers, each with many variants. The devastating effects of cancer on patients and their families extract a huge loss. For instance, nearly 1.5 million people in the US alone are diagnosed with cancer every year. The importance of cancer diagnosis and subsequent treatment has long been recognized (1 ). In spite of progresses in understanding cancer, treatment has remained almost unchanged for the past few decades. Based on statistics from 2003, the death rates from cancer were about the same as in the 1950s. The 3 most frequently used treatments— chemotherapy, radiation, and surgery— destroy not only cancerous cells and tissues but also healthy ones, and one must wait for any reappearance of cancer to learn whether the treatment has worked. Since the early 2000s, the revolutionary work in emerging nanomaterials and nanotechnology has attracted many chemists, materials scientists, biologists, and oncologists to develop new technologies for cancer therapy. Nanomaterials have a size dimension close to the scale of molecules, opening many opportunities for cancer diagnosis, tumor imaging, and drug treatment, even when these malignancies are at their earliest latent stages. These exciting opportunities greatly inspired researchers’ efforts in combining nanotechnology with oncology. For instance, in 2003, Chad Mirkin and coworkers reported a new detection method for prostate specific antigen using gold nanoparticles and coded short DNA strands (2 ). The analytical sensitivity of this technology was up to a million times better than that of conventional ELISA assays, and the biotech company Nanosphere planned to commercialize this diagnostic technique.
1
Laboratory of Advanced Materials, Department of Chemistry, Collaborative Innovation Center for Energy Materials, Fudan University, Shanghai, China. * Address correspondence to this author at: Laboratory of Advanced Materials, Department of Chemistry, Collaborative Innovation Center for Energy Materials, Fudan University, Shanghai, 200433, China. E-mail [email protected]. 2 This article has been cited more than 1200 times since publication. Received January 3, 2015; accepted January 12, 2015. DOI: 10.1373/clinchem.2014.237453 © 2015 American Association for Clinical Chemistry
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In 2004, the National Cancer Institute (NCI)3 launched a $144 million cancer research nanotechnology initiative, $26.3 million of which was funded during the first year to 7 centers that were designed to promote interdisciplinary work among different research fields. Andrew von Eschenbach, former director of the NCI, said, “The future of oncology—and the opportunity to eliminate the suffering and death due to cancer—will hinge upon our ability to confront cancer at its molecular level.” In the meantime, Europe and Japan were also putting substantial research investment and human capital into finding new tools for cancer diagnosis and treatment, with comparable amounts of money to the NCI. In addition, this exciting field also attracted several companies, such as StarPharma, Introgen, and Nanosphere, to actively join. For instance, there were 8 nanoparticle-based imaging agents and therapeutics either on the market, in clinical trials, or awaiting clinical trials by 2005. “The science in this area is exploding,” said Gregory Downing, the head of NCI’s Office of Technology and Industrial Relations at that time. In September 2004, our research group at Harvard University, led by Professor Charles Lieber, first demonstrated the electrical detection of single viruses using silicon nanowire (SiNW) field effect transistor (FET) arrays (3 ). In October 2005, our group reported this featured work in the development of an electrical sensor chip made of an array of hundreds of SiNW FETs, each functionalized with a particular antibody for selected cancer marker proteins, such as prostate specific antigens. When the target antigen binds to its specific antibody, the electrical conductance of the SiNW FETs changes, similar to applying a voltage to the gate electrode of a conventional FET. This method allows the detection of biomarker proteins with high analytical sensitivity and selectively and a rapid, reproducible readout. The success of this technology requires synthesis of semiconductor nanowires with high quality, fabrication of nanodevice arrays with good reproducibility, and reliable surface chemical functionalization, which have since been reported in detail (4 ). Many other research groups, in the ensuing years, have demonstrated excellent work of using nanomaterials interfaced with nanoelectrode arrays for the electrical de-
3
Nonstandard abbreviations: NCI, National Cancer Institute; SiNW, silicon nanowire; FET, field effect transistor.
Citation Classic tection of cancer marker proteins. Advances in diagnostics are well under way in many laboratories around the world.
Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.
Authors’ Disclosures or Potential Conflicts of Interest: No authors declared any potential conflicts of interest.
References 1. Etzioni R, Urban N, Ramsey S, McIntosh M, Schwartz S, Reid B, et al. The case for early detection. Nat Rev Cancer 2003;3:1–10. 2. Nam JM, Thaxton CS, Mirkin CA. Nanoparticle-based bio-bar-codes for the ultrasensitive detection of proteins. Science 2003;301:1884 – 6. 3. Patolsky F, Zheng G, Hayden O, Lakadamyali M, Zhuang X, Lieber CM. Electrical detection of single viruses. Proc Natl Acad Sci U S A 2004;101:14017–22. 4. Patolsky F, Zheng G, Lieber CM. Fabrication of silicon nanowire devices for ultrasensitive, label-free, real-time detection of biological and chemical species. Nat Protocols 2006;1:1711–24.
Clinical Chemistry 61:4 (2015) 665
Clinical Chemistry 61:4 664–665 (2015)
Nanoelectronics Aiming at Cancer Gengfeng Zheng1*
Featured Article: Zheng GF, Patolsky F, Cui Y, Wang WU, Lieber CM. Multiplexed electrical detection of cancer markers with nanowire sensor arrays. Nat Biotechnol 2005;23:1294 –301.2 There are ⬎200 types of cancers, each with many variants. The devastating effects of cancer on patients and their families extract a huge loss. For instance, nearly 1.5 million people in the US alone are diagnosed with cancer every year. The importance of cancer diagnosis and subsequent treatment has long been recognized (1 ). In spite of progresses in understanding cancer, treatment has remained almost unchanged for the past few decades. Based on statistics from 2003, the death rates from cancer were about the same as in the 1950s. The 3 most frequently used treatments— chemotherapy, radiation, and surgery— destroy not only cancerous cells and tissues but also healthy ones, and one must wait for any reappearance of cancer to learn whether the treatment has worked. Since the early 2000s, the revolutionary work in emerging nanomaterials and nanotechnology has attracted many chemists, materials scientists, biologists, and oncologists to develop new technologies for cancer therapy. Nanomaterials have a size dimension close to the scale of molecules, opening many opportunities for cancer diagnosis, tumor imaging, and drug treatment, even when these malignancies are at their earliest latent stages. These exciting opportunities greatly inspired researchers’ efforts in combining nanotechnology with oncology. For instance, in 2003, Chad Mirkin and coworkers reported a new detection method for prostate specific antigen using gold nanoparticles and coded short DNA strands (2 ). The analytical sensitivity of this technology was up to a million times better than that of conventional ELISA assays, and the biotech company Nanosphere planned to commercialize this diagnostic technique.
1
Laboratory of Advanced Materials, Department of Chemistry, Collaborative Innovation Center for Energy Materials, Fudan University, Shanghai, China. * Address correspondence to this author at: Laboratory of Advanced Materials, Department of Chemistry, Collaborative Innovation Center for Energy Materials, Fudan University, Shanghai, 200433, China. E-mail [email protected]. 2 This article has been cited more than 1200 times since publication. Received January 3, 2015; accepted January 12, 2015. DOI: 10.1373/clinchem.2014.237453 © 2015 American Association for Clinical Chemistry
664
In 2004, the National Cancer Institute (NCI)3 launched a $144 million cancer research nanotechnology initiative, $26.3 million of which was funded during the first year to 7 centers that were designed to promote interdisciplinary work among different research fields. Andrew von Eschenbach, former director of the NCI, said, “The future of oncology—and the opportunity to eliminate the suffering and death due to cancer—will hinge upon our ability to confront cancer at its molecular level.” In the meantime, Europe and Japan were also putting substantial research investment and human capital into finding new tools for cancer diagnosis and treatment, with comparable amounts of money to the NCI. In addition, this exciting field also attracted several companies, such as StarPharma, Introgen, and Nanosphere, to actively join. For instance, there were 8 nanoparticle-based imaging agents and therapeutics either on the market, in clinical trials, or awaiting clinical trials by 2005. “The science in this area is exploding,” said Gregory Downing, the head of NCI’s Office of Technology and Industrial Relations at that time. In September 2004, our research group at Harvard University, led by Professor Charles Lieber, first demonstrated the electrical detection of single viruses using silicon nanowire (SiNW) field effect transistor (FET) arrays (3 ). In October 2005, our group reported this featured work in the development of an electrical sensor chip made of an array of hundreds of SiNW FETs, each functionalized with a particular antibody for selected cancer marker proteins, such as prostate specific antigens. When the target antigen binds to its specific antibody, the electrical conductance of the SiNW FETs changes, similar to applying a voltage to the gate electrode of a conventional FET. This method allows the detection of biomarker proteins with high analytical sensitivity and selectively and a rapid, reproducible readout. The success of this technology requires synthesis of semiconductor nanowires with high quality, fabrication of nanodevice arrays with good reproducibility, and reliable surface chemical functionalization, which have since been reported in detail (4 ). Many other research groups, in the ensuing years, have demonstrated excellent work of using nanomaterials interfaced with nanoelectrode arrays for the electrical de-
3
Nonstandard abbreviations: NCI, National Cancer Institute; SiNW, silicon nanowire; FET, field effect transistor.
Citation Classic tection of cancer marker proteins. Advances in diagnostics are well under way in many laboratories around the world.
Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.
Authors’ Disclosures or Potential Conflicts of Interest: No authors declared any potential conflicts of interest.
References 1. Etzioni R, Urban N, Ramsey S, McIntosh M, Schwartz S, Reid B, et al. The case for early detection. Nat Rev Cancer 2003;3:1–10. 2. Nam JM, Thaxton CS, Mirkin CA. Nanoparticle-based bio-bar-codes for the ultrasensitive detection of proteins. Science 2003;301:1884 – 6. 3. Patolsky F, Zheng G, Hayden O, Lakadamyali M, Zhuang X, Lieber CM. Electrical detection of single viruses. Proc Natl Acad Sci U S A 2004;101:14017–22. 4. Patolsky F, Zheng G, Lieber CM. Fabrication of silicon nanowire devices for ultrasensitive, label-free, real-time detection of biological and chemical species. Nat Protocols 2006;1:1711–24.
Clinical Chemistry 61:4 (2015) 665
