High sensitivity cardiac troponin I detection in physiological environment using AlGaN/GaN High Electron Mobility Transistor (HEMT) Biosensors

Sarangadharan, Indu; Regmi, Abiral; Chen, Yen Wen; Hsu, Cheng-Wei; Chen, Pei Chi; Chang, Wen Hsin; Lee, Geng Yen; Chyi, Jen Inn; Shiesh, Shu Chu; Lee, Gwo‐Bin; Wang, Yu Lin

doi:10.1016/j.bios.2017.09.018

Cited by 138 publications

(75 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Such sample pretreatments, however, are not ideal when highly sensitive detection is required for PoC diagnostic devices. Thus, a number of works have tried to address this Debye screening problem in situ for FET‐based measurements . One of these strategies is by coimmobilization of the biorecognition molecule and a polymer polyethylene glycol (PEG) on the surface of the sensor, which has made FET‐based detection of proteins in high ionic strength buffer feasible .…”

Section: Introductionmentioning

confidence: 99%

Graphene‐Based Electronic Immunosensor with Femtomolar Detection Limit in Whole Serum

Andoy

Filipiak

Vetter

et al. 2018

Adv Materials Technologies

View full text Add to dashboard Cite

Purely electronic diagnostic devices that are sensitive to biomolecules' intrinsic charge present a very attractive platform for point‐of‐care (PoC) applications, since they can operate under label‐free conditions. In this report, a graphene‐based electrolyte‐gated field‐effect transistor is developed as an immunosensor capable of sensitive analyte detection, even in the complex environment of physiological samples. The coimmobilization of an antibody fragment (F(ab′)2) and polyethylene glycol on the graphene surface allows for a highly sensitive and selective detection of a protein analyte, with a limit of detection in the low femtomolar range, both in high ionic strength buffer and undiluted serum. Multiparametric analysis of the device's analyte‐dependent electronic response shows that the mechanism behind this very sensitive detection cannot be explained by a commonly reported electrostatic gating effect. Rather, the observed combination of charge neutrality point shifts and asymmetric mobility changes are attributed to the modulation of scattering by charged impurities, which seem to dominate the device's transfer characteristics. Furthermore, the reproducibility of the normalized signal response obtained from several different devices shows that this graphene‐based immunosensor is capable of direct and quantitative measurements of protein analytes in untreated serum, imperative for diagnostic tools geared toward PoC applications.

show abstract

Section: Introductionmentioning

confidence: 99%

Graphene‐Based Electronic Immunosensor with Femtomolar Detection Limit in Whole Serum

Andoy

Filipiak

Vetter

et al. 2018

Adv Materials Technologies

View full text Add to dashboard Cite

show abstract

“…The working principle of our GaN HEMT biosensor is detailed in our previous works [16,17,18]. Briefly, when the test solutions containing high salt concentration (physiological salt concentration is ~150 mM) are dropped on the sensor surface and a pulsed gate voltage is applied, the electrical double layer (EDL) on the solid/liquid interfaces (the interfaces of solution and gate electrode and channel) is re-distributed, generating a solution capacitance.…”

Section: Resultsmentioning

confidence: 99%

“…Due to severe charge screening effect in physiological salt solution, the potential changes induced by receptor-ligand binding cannot modulate the channel conductivity, which is the reason for demanding extensive sample pre-treatments while using traditional FET biosensors [12,13,14,15]. But using our sensing structure, we have been able to overcome the charge screening effect and directly detect biological targets and ionic species in high salt concentration environments [16,17,18,28]. In our sensor design, we can enhance the sensitivity of our HEMT biosensor to EVs in physiological salt environment.…”

Section: Resultsmentioning

confidence: 99%

“…However, clinical applications of FET biosensors were limited due to the charge screening effect in high ionic strength solutions such as physiological fluids which demand extensive sample pre-treatments [13,14,15]. In our previous works, we developed a new FET bio-sensing methodology using AlGaN/GaN high electron mobility transistor (HEMT) for protein detection in physiological salt concentration [16,17,18]. We were able to directly detect target proteins in clinical sera, even with the presence of large quantities of non-specific proteins in the plasma proteome.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Miniaturized Biomedical Sensors for Enumeration of Extracellular Vesicles

Pulikkathodi

Sarangadharan

et al. 2018

IJMS

Self Cite

View full text Add to dashboard Cite

In this research, we have realized a rapid extracellular vesicle (EV) quantification methodology using a high field modulated AlGaN/GaN high electron mobility (HEMT) biosensor. The unique sensing structure facilitated the detection of the sub-cellular components in physiological salt environment without requiring extensive sample pre-treatments. The high field operation of GaN HEMT biosensor provides high sensitivity and wide dynamic range of detection of EVs (107–1010 EVs/mL). An antibody specific to the known surface marker on the EV was used to capture them for quantification using an HEMT biosensor. Fluorescence microscopy images confirm the successful capture of EVs from the test solution. The present method can detect EVs in high ionic strength solution, with a short sample incubation period of 5 min, and does not require labels or additional reagents or wash/block steps. This methodology has the potential to be used in clinical applications for rapid EV quantification from blood or serum for the development of diagnostic and prognostic tools.

show abstract

“…Sarangadharan et al [79,80] reported an electrical double-layer gated high-field AlGaN/GaN HEMT biosensor in which the gating mechanism overcomes charge screening effects that are prevalent in traditional field effect transistor (FET)-based biosensors, allowing detection of target proteins in physiological solutions. They were able to detect troponin I in blood samples in the range 0.006À148 ng/mL, using antibody or aptamer functionalization [79,80]. The cover glass approach leads to an increase in the pulsed current, as shown in Fig.…”

Section: Troponinmentioning

confidence: 99%