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Proc Natl Acad Sci U S A. 2015 Aug 11;112(32):E4354-63. doi: 10.1073/pnas.1510824112. Epub 2015 Jul 20.

Multitarget, quantitative nanoplasmonic electrical field-enhanced resonating device (NE2RD) for diagnostics.

Author information

1
Demirci Bio-Acoustic-Microelectromechanical Systems in Medicine (BAMM) Laboratory, Canary Center at Stanford for Cancer Early Detection, Radiology Department, Stanford University School of Medicine, Palo Alto, CA 94304;
2
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115;
3
Demirci Bio-Acoustic-Microelectromechanical Systems in Medicine (BAMM) Laboratory, Canary Center at Stanford for Cancer Early Detection, Radiology Department, Stanford University School of Medicine, Palo Alto, CA 94304; jeanne.thompson@stanford.edu utkan@stanford.edu.
4
Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94304; Stanford Genome Technology Center, Stanford University, Palo Alto, CA 94304;
5
Demirci Bio-Acoustic-Microelectromechanical Systems in Medicine (BAMM) Laboratory, Canary Center at Stanford for Cancer Early Detection, Radiology Department, Stanford University School of Medicine, Palo Alto, CA 94304; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, 310003, China; Institute for Translational Medicine, Zhejiang University, Hangzhou, Zhejiang, 310029, China;
6
Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115;
7
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115;
8
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115;
9
Laboratory of Genital Tract Biology, Department of Obstetrics, Gynecology, Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115;
10
Molecular Imaging Program at Stanford, Center for Cancer Nanotechnology Excellence, Stanford University, Palo Alto, CA 94305; Department of Radiology, Stanford University School of Medicine, Stanford, CA 94304;
11
Department of Medicine, Harvard Medical School, Boston, MA 02115; Department of Radiology, Stanford University School of Medicine, Stanford, CA 94304;
12
Singapore Immunology Network, Agency for Science Technology and Research (A*STAR), Singapore 138648;
13
Department of Neurology, Beth Israel Deaconess Medical Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115;
14
Stanford Genome Technology Center, Stanford University, Palo Alto, CA 94304;
15
Molecular Imaging Program at Stanford, Center for Cancer Nanotechnology Excellence, Stanford University, Palo Alto, CA 94305; Department of Radiology, Stanford University School of Medicine, Stanford, CA 94304; Department of Bioengineering, Stanford University, Stanford, CA 94305; Department of Materials Science and Engineering, Stanford University, Stanford, CA 94305; Bio-X Program, Stanford University, Stanford, CA, 94305;
16
Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94304; Stanford Genome Technology Center, Stanford University, Palo Alto, CA 94304; jeanne.thompson@stanford.edu utkan@stanford.edu.
17
Demirci Bio-Acoustic-Microelectromechanical Systems in Medicine (BAMM) Laboratory, Canary Center at Stanford for Cancer Early Detection, Radiology Department, Stanford University School of Medicine, Palo Alto, CA 94304; Department of Electrical Engineering (By courtesy), Stanford University, Stanford, CA 94305 jeanne.thompson@stanford.edu utkan@stanford.edu.

Abstract

Recent advances in biosensing technologies present great potential for medical diagnostics, thus improving clinical decisions. However, creating a label-free general sensing platform capable of detecting multiple biotargets in various clinical specimens over a wide dynamic range, without lengthy sample-processing steps, remains a considerable challenge. In practice, these barriers prevent broad applications in clinics and at patients' homes. Here, we demonstrate the nanoplasmonic electrical field-enhanced resonating device (NE(2)RD), which addresses all these impediments on a single platform. The NE(2)RD employs an immunodetection assay to capture biotargets, and precisely measures spectral color changes by their wavelength and extinction intensity shifts in nanoparticles without prior sample labeling or preprocessing. We present through multiple examples, a label-free, quantitative, portable, multitarget platform by rapidly detecting various protein biomarkers, drugs, protein allergens, bacteria, eukaryotic cells, and distinct viruses. The linear dynamic range of NE(2)RD is five orders of magnitude broader than ELISA, with a sensitivity down to 400 fg/mL This range and sensitivity are achieved by self-assembling gold nanoparticles to generate hot spots on a 3D-oriented substrate for ultrasensitive measurements. We demonstrate that this precise platform handles multiple clinical samples such as whole blood, serum, and saliva without sample preprocessing under diverse conditions of temperature, pH, and ionic strength. The NE(2)RD's broad dynamic range, detection limit, and portability integrated with a disposable fluidic chip have broad applications, potentially enabling the transition toward precision medicine at the point-of-care or primary care settings and at patients' homes.

KEYWORDS:

biodetection; label-free; multiple biotargets; nanoparticle; point-of-need

PMID:
26195743
PMCID:
PMC4538635
DOI:
10.1073/pnas.1510824112
[Indexed for MEDLINE]
Free PMC Article

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