Microneedle biosensor: A method for direct label-free real time protein detection

Esfandyarpour, Rahim; Esfandyarpour, Hesaam; Javanmard, Mehdi; Harris, James S.; Davis, Ronald W.

doi:10.1016/j.snb.2012.11.064

Cited by 65 publications

(43 citation statements)

References 31 publications

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“…We patterned the nanoneedle bundles by etching the 200 nm top-SiO 2 layer; 100 nm top pþ-silicon layer, and 30 nm middle oxide layer,100nmpþ-silicon layer down to bottom oxide layer. [53][54][55][56][57] We performed wet etch step to etch out the channel below the bundle of nanoneedles. Afterwards, we performed another etch step to expose the bonding pads to allow wire bonding.…”

Section: A Device Fabricationmentioning

confidence: 99%

Label-free electronic probing of nucleic acids and proteins at the nanoscale using the nanoneedle biosensor

Esfandyarpour

Javanmard²,

Koochak

et al. 2013

Biomicrofluidics

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Detection of proteins and nucleic acids is dominantly performed using optical fluorescence based techniques, which are more costly and timely than electrical detection due to the need for expensive and bulky optical equipment and the process of fluorescent tagging. In this paper, we discuss our study of the electrical properties of nucleic acids and proteins at the nanoscale using a nanoelectronic probe we have developed, which we refer to as the Nanoneedle biosensor. The nanoneedle consists of four thin film layers: a conductive layer at the bottom acting as an electrode, an oxide layer on top, and another conductive layer on top of that, with a protective oxide above. The presence of proteins and nucleic acids near the tip results in a decrease in impedance across the sensing electrodes. There are three basic mechanisms behind the electrical response of DNA and protein molecules in solution under an applied alternating electrical field. The first change stems from modulation of the relative permittivity at the interface. The second mechanism is the formation and relaxation of the induced dipole moment. The third mechanism is the tunneling of electrons through the biomolecules. The results presented in this paper can be extended to develop low cost point-of-care diagnostic assays for the clinical setting. V C 2013 AIP Publishing LLC. [http://dx

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Section: A Device Fabricationmentioning

confidence: 99%

Label-free electronic probing of nucleic acids and proteins at the nanoscale using the nanoneedle biosensor

Esfandyarpour

Javanmard²,

Koochak

et al. 2013

Biomicrofluidics

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“…Various miniaturization techniques have been introduced for detection of proteins [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20], nucleic acids [10,16,21], and cells [22][23][24][25][26][27]. These techniques are unsuitable for metabolites because tagging the metabolite with beads or a fluorophore would alter the structure significantly and affect the binding of the target metabolite to the probe antibody.…”

Section: Metabolite Detectionmentioning

confidence: 99%

Surface-enhanced Raman scattering (SERS) for detection of phenylketonuria for newborn screening

Javanmard

Davis

2014

Nanoscale Imaging, Sensing, and Actuation for Biomedical Applications XI

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Diagnosis of Phenylketonuria (PKU) in newborns is important because it can potentially help prevent mental retardation since it is treatable by dietary means. PKU results in phenylketonurics having phenylalanine levels as high as 2 mM whereas the normal upper limit in healthy newborns is 120 uM. To this end, we are developing a microfluidic platform integrated with a SERS substrate for detection of high levels of phenylalanine. We have successfully demonstrated SERS detection of phenylalanine using various SERS substrates fabricated using nanosphere lithography, which exhibit high levels of field enhancement. We show detection of SERS at clinically relevant levels.

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“…Several electrochemical genosensors have been reported that have nanomolar-range sensitivity, but all to date rely on labeling techniques (Kannan 2011; Hashemi Rafsanjani et al 2010). Labeling is an expensive, time-consuming, and labor-intensive procedure that introduces additional uncertain sources of error to the measurements (Esfandyarpour et al 2013; Kricka 2002). Silicon Nanowires (SiNWs), one of the more sensitive and selective technologies for the detection of DNA hybridization, is quite limited in throughput (Park et al 2002; Li et al 2004; Li et al 2005; Xie 2012; Cui et al 2001; Zhang et al 2008; Gao 2007).…”

Section: Introductionmentioning

confidence: 99%

Nanoelectronic three-dimensional (3D) nanotip sensing array for real-time, sensitive, label-free sequence specific detection of nucleic acids

Esfandyarpour¹,

Yang

Koochak

et al. 2016

Biomed Microdevices

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The improvements in our ability to sequence and genotype DNA have opened up numerous avenues in the understanding of human biology and medicine with various applications, especially in medical diagnostics. But the realization of a label free, real time, high-throughput and low cost biosensing platforms to detect molecular interactions with a high level of sensitivity has been yet stunted due to two factors: one, slow binding kinetics caused by the lack of probe molecules on the sensors and two, limited mass transport due to the planar structure (two-dimensional) of the current biosensors. Here we present a novel three-dimensional (3D), highly sensitive, real-time, inexpensive and label-free nanotip array as a rapid and direct platform to sequence-specific DNA screening. Our nanotip sensors are designed to have a nano sized thin film as their sensing area (~ 20 nm), sandwiched between two sensing electrodes. The tip is then conjugated to a DNA oligonucleotide complementary to the sequence of interest, which is electrochemically detected in real-time via impedance changes upon the formation of a double-stranded helix at the sensor interface. This 3D configuration is specifically designed to improve the biomolecular hit rate and the detection speed. We demonstrate that our nanotip array effectively detects oligonucleotides in a sequence-specific and highly sensitive manner, yielding concentration-dependent impedance change measurements with a target concentration as low as 10 pM and discrimination against even a single mismatch. Notably, our nanotip sensors achieve this accurate, sensitive detection without relying on signal indicators or enhancing molecules like fluorophores. It can also easily be scaled for highly multiplxed detection with up to 5000 sensors/square centimeter, and integrated into microfluidic devices. The versatile, rapid, and sensitive performance of the nanotip array makes it an excellent candidate for point-of-care diagnostics, and high-throughput DNA analysis applications.

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Microneedle biosensor: A method for direct label-free real time protein detection

Cited by 65 publications

References 31 publications

Label-free electronic probing of nucleic acids and proteins at the nanoscale using the nanoneedle biosensor

Label-free electronic probing of nucleic acids and proteins at the nanoscale using the nanoneedle biosensor

Surface-enhanced Raman scattering (SERS) for detection of phenylketonuria for newborn screening

Nanoelectronic three-dimensional (3D) nanotip sensing array for real-time, sensitive, label-free sequence specific detection of nucleic acids

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