Label-free biomarker detection from whole blood

Stern, Eric; Vacic, Aleksandar; Rajan, Nitin K.; Criscione, Jason M.; Park, Jason; Fahmy, Tarek M.; Reed, Mark A.

doi:10.1109/icsict.2010.5667621

Cited by 103 publications

(135 citation statements)

References 8 publications

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“…In short, the screening length in physiological solutions, <1 nm, reduces the field produced by charged macromolecules at the FET surface and thus makes real-time label-free detection difficult. The first method reported to overcome this intrinsic limitation of FET biosensors involved desalting to enable subsequent low-ionic-strength detection (8,20), although this also precludes true real-time measurements. Truncated antibody receptors (21) and small aptamers (22) also have been used to reduce the distance between target species and the FET surfaces, although the generality of such methods for real-time sensing in physiological conditions requires further study.…”

mentioning

confidence: 99%

Specific detection of biomolecules in physiological solutions using graphene transistor biosensors

Gao

Yang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

221

236

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Nanomaterial-based field-effect transistor (FET) sensors are capable of label-free real-time chemical and biological detection with high sensitivity and spatial resolution, although direct measurements in high-ionic-strength physiological solutions remain challenging due to the Debye screening effect. Recently, we demonstrated a general strategy to overcome this challenge by incorporating a biomoleculepermeable polymer layer on the surface of silicon nanowire FET sensors. The permeable polymer layer can increase the effective screening length immediately adjacent to the device surface and thereby enable real-time detection of biomolecules in high-ionic-strength solutions. Here, we describe studies demonstrating both the generality of this concept and application to specific protein detection using graphene FET sensors. Concentration-dependent measurements made with polyethylene glycol (PEG)-modified graphene devices exhibited real-time reversible detection of prostate specific antigen (PSA) from 1 to 1,000 nM in 100 mM phosphate buffer. In addition, comodification of graphene devices with PEG and DNA aptamers yielded specific irreversible binding and detection of PSA in pH 7.4 1x PBS solutions, whereas control experiments with proteins that do not bind to the aptamer showed smaller reversible signals. In addition, the active aptamer receptor of the modified graphene devices could be regenerated to yield multiuse selective PSA sensing under physiological conditions. The current work presents an important concept toward the application of nanomaterial-based FET sensors for biochemical sensing in physiological environments and thus could lead to powerful tools for basic research and healthcare.field-effect transistor | Debye screening | surface modification | DNA aptamer receptor | polyethylene glycol N anoelectronic biosensors offer broad capabilities for label-free high-sensitivity real-time detection of biological species that are important to both fundamental research and biomedical applications (1-6). In particular, field-effect transistor (FET) biosensors configured from semiconducting nanowires (1, 2), single-walled carbon nanotubes (1, 3, 4), and graphene (1, 5, 6) have been extensively investigated since the first report of real-time protein detection using silicon nanowire devices (7). Subsequent studies have demonstrated highly sensitive and in some cases multiplexed detection of key analytes, including protein disease markers (8-10), nucleic acids (11-13), and viruses (14), as well as detection of protein-protein interactions (8,(15)(16)(17) and enzymatic activity (8).The success achieved with nanomaterial-based FET biosensors has been limited primarily to measurements in relatively low-ionicstrength nonphysiological solutions due to the Debye screening length (18,19). In short, the screening length in physiological solutions, <1 nm, reduces the field produced by charged macromolecules at the FET surface and thus makes real-time label-free detection difficult. The first method reported to overcome this ...

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mentioning

confidence: 99%

Specific detection of biomolecules in physiological solutions using graphene transistor biosensors

Gao

Yang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

221

236

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“…2,3 In particular, researchers around the world have been tailor-making a multitude of nanomaterials-based electrical biosensors and developing new strategies to apply them in ultrasensitive biosensing. Examples of such nanomaterials include carbon nanotubes, [4][5][6][7][8][9][10][11][12][13] nanowires, 11,[14][15][16][17][18][19][20][21] nanoparticles, 6,[22][23][24][25] nanopores, 26,27 nanoclusters 28 and graphene. 5,[29][30][31][32] Compared with conventional optical, biochemical and biophysical methods, nanomaterial-based electronic biosensing offers significant advantages, such as high sensitivity and new sensing mechanisms, high spatial resolution for localized detection, facile integration with standard wafer-scale semiconductor processing and label-free, real-time detection in a nondestructive manner.…”

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confidence: 99%

Carbon nanomaterials field-effect-transistor-based biosensors

2012

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Carbon nanomaterials field-effect transistor (FET)-based electrical biosensors provide significant advantages over the current gold standards, holding great potential for realizing direct, label-free, real-time electrical detection of biomolecules in a multiplexed manner with ultrahigh sensitivity and excellent selectivity. The feasibility of integrating them with current complementary metal oxide semiconductor platform and a fluid handling module using standard microfabrication technology opens up new opportunities for the development of low-cost, low-noise, portable electrical biosensors for use in practical future devices. In this article, we review recent progress in the rapidly developing area of biomolecular interaction detection using FET-based biosensors based on the carbon nanomaterials single-walled carbon nanotubes (SWNTs) and graphene. Detection scenarios include DNA-DNA hybridization, DNA-protein interaction, protein function and cellular activity. In particular, we will highlight an amazing property of SWNT-or graphene-FETs in biosensing: their ability to detect biomolecules at the single-molecule level or at the single-cell level. This is due to the size comparability and the surface compatibility of the carbon nanomaterials with biological molecules. We also summarize some current challenges the scientific community is facing, including device-to-device heterogeneity and the lack of system integration for uniform device array mass production. Keywords: biosensor; carbon nanotube; field-effect transistor; graphene A biosensor is an analytical device that incorporates a biological recognition element in direct spatial contact with a transduction element. This integration ensures the rapid and convenient conversion of the biological events to detectable signals. 1 With the discovery of rich nanomaterials and the development of exquisite nanofabrication tools, such as electron beam lithography, focused ion beam and nanoimprint lithography, new avenues have been opened up in the field of biosensors in the last two decades. 2,3 In particular, researchers around the world have been tailor-making a multitude of nanomaterials-based electrical biosensors and developing new strategies to apply them in ultrasensitive biosensing. Examples of such nanomaterials include carbon nanotubes, 4-13 nanowires, 11,14-21 nanoparticles, 6,22-25 nanopores, 26,27 nanoclusters 28 and graphene. 5,[29][30][31][32] Compared with conventional optical, biochemical and biophysical methods, nanomaterial-based electronic biosensing offers significant advantages, such as high sensitivity and new sensing mechanisms, high spatial resolution for localized detection, facile integration with standard wafer-scale semiconductor processing and label-free, real-time detection in a nondestructive manner.Among diverse electrical biosensing architectures, devices based on field-effect transistors (FETs) have attracted great attention because they are an ideal biosensor that can directly translate the interactions between target biological mole...

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“…Another system reported by Stern et al (13) uses a two-step approach, incorporating microfluidic purification chips that capture multiple biomarkers from whole blood, concentrating the biomarkers of interest and releasing the biomarkers for quantitative detection with silicon nanoribbon detectors. This technique reduces the minimum required sensitivity of the system (13).…”

Section: Nanowiresmentioning

confidence: 99%

Advances in the application of nanotechnology in the diagnosis and treatment of gastrointestinal tumors

Sun

Fang

et al. 2014

Molecular and Clinical Oncology

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Abstract. Nanotechnology has broad application prospects in the diagnosis and treatment of cancer. Integrating chemistry, engineering, biology and medicine, nanotechnology is a multidisciplinary research field. Nanoscale imaging technology significantly improves the precision and accuracy of tumor diagnosis. Nanocarriers are able to significantly improve the accuracy of dose and targeted drug delivery and reduce the toxic side effects. This review focuses on the emerging roles of these innovative technologies in gastrointestinal cancer diagnostics and therapeutics. Although several problems and barriers are hampering the development of nanodevices, the potential for nanotechnologies to function as multimodal nanotheranostic agents will likely pave the way for the fight against gastrointestinal cancer.

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Label-free biomarker detection from whole blood

Cited by 103 publications

References 8 publications

Specific detection of biomolecules in physiological solutions using graphene transistor biosensors

Specific detection of biomolecules in physiological solutions using graphene transistor biosensors

Carbon nanomaterials field-effect-transistor-based biosensors

Advances in the application of nanotechnology in the diagnosis and treatment of gastrointestinal tumors

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