Abstract
We present a review of field effect transistors (FET) from the point of view of their applications to label-free sensing in the era of genomics and proteomics. Here, rather than a collection of Bio-FET achievements, we propose an analysis of the different issues hampering the use of these devices into clinical applications. We make a particular emphasis on the influence of the sensor geometry in the phenomena of mass transport of analytes, which is a topic that has been traditionally overlooked in the analysis and design of biosensors, but that plays a central role in the achievement of low limits of detection. Other issues like the screening of charges by the ions in liquids with physiological ionic strength and the non-specific binding are also reviewed. In conclusion, we give an overview of different solutions that have been proposed to address all these challenges, demonstrating the potential of field effect transistors owing to their ease of integration with other semiconductor components for developing cost-effective, highly multiplexed sensors for next-generation medicines.
Similar content being viewed by others
References
Abouzar MH, Poghossian A, Pedraza AM, Gandhi D, Ingebrandt S, Moritz W, Schöning MJ (2011) An array of field-effect nanoplate SOI capacitors for (bio-)chemical sensing. Biosens Bioelectron 26:3023–3028
Abouzar MH, Poghossian A, Cherstvy AG, Pedraza AM, Ingebrandt S, Schöning MJ (2012) Label-free electrical detection of DNA by means of field-effect nanoplate capacitors: experiments and modeling. Phys Status Solidi A 209:925–934
Accastelli E, Scarbolo P, Ernst T, Palestri P, Selmi L, Guiducci C (2016) Multi-wire tri-gate silicon nanowires reaching milli-pH unit resolution in one micron square footprint. Biosensors 6:9
Adam T, Hashim U (2015) Highly sensitive silicon nanowire biosensor with novel liquid gate control for detection of specific single-stranded DNA molecules. Biosens Bioelectron 67:656–661
Allen BL, Kichambare PD, Star A (2007) Carbon nanotube field-effect-transistor-based biosensors. Adv Mater 19:1439–1451
Balasubramanian K (2010) Challenges in the use of 1D nanostructures for on-chip biosensing and diagnostics: a review. Biosens Bioelectron 26:1195–1204
Bedner K et al (2014) Investigation of the dominant 1/f noise source in silicon nanowire sensors. Sensors Actuators B Chem 191:270–275
Bergveld P (1970) Development of an ion-sensitive solid-state device for neurophysiological measurements. IEEE Trans Biomed Eng 17:70–71
Bergveld P (2003) Thirty years of ISFETOLOGY: what happened in the past 30 years and what may happen in the next 30 years. Sensors Actuators B Chem 88:1–20
Braeken D, Reekmans G, Zhou C, Van Meerbergen B, Callewaert G, Borghs G, Bartic C (2008) Electronic DNA hybridisation detection in low-ionic strength solutions. J Exp Nanosci 3:157–169
Cai B, Wang S, Huang L, Ning Y, Zhang Z, Zhang G-J (2014) Ultrasensitive label-free detection of PNA–DNA hybridization by reduced graphene oxide field-effect transistor biosensor. ACS Nano 8:2632–2638
Caras S, Janata J (1980) Field effect transistor sensitive to penicillin. Anal Chem 52:1935–1937
Chandramouli K, Qian P-Y (2009) Proteomics: challenges, techniques and possibilities to overcome biological sample complexity. Hum Genomic Proteomic 2009:239204
Chang H-K, Ishikawa FN, Zhang R, Datar R, Cote RJ, Thompson ME, Zhou C (2011) Rapid, label-free, electrical whole blood bioassay based on nanobiosensor systems. ACS Nano 5:9883–9891
Chu C-H et al (2017) Beyond the Debye length in high ionic strength solution: direct protein detection with field-effect transistors (FETs) in human serum. Sci Rep 7:5256
Cui Y, Wei Q, Park H, Lieber CM (2001) Nanowire nanosensors for highly sensitive and selective detection of biological and chemical species. Science 293:1289–1292
Deen MJ, Shinwari MW, Ranuárez JC, Landheer D (2006) Noise considerations in field-effect biosensors. J Appl Phys 100:074703
Dorvel BR, Reddy B, Go J, Duarte Guevara C, Salm E, Alam MA, Bashir R (2012) Silicon nanowires with high-k hafnium oxide dielectrics for sensitive detection of small nucleic acid oligomers. ACS Nano 6:6150–6164
Duan X, Li Y, Rajan NK, Routenberg DA, Modis Y, Reed MA (2012) Quantification of the affinities and kinetics of protein interactions using silicon nanowire biosensors. Nat Nanotechnol 7:401
Elnathan R et al (2012) Biorecognition layer engineering: overcoming screening limitations of nanowire-based FET devices. Nano Lett 12:5245–5254
Freeman R, Elbaz J, Gill R, Zayats M, Willner I (2007) Analysis of dopamine and tyrosinase activity on ion-sensitive field-effect transistor (ISFET) devices. Chem Eur J 13:7288–7293
Gao A et al (2011) Silicon-nanowire-based CMOS-compatible field-effect transistor nanosensors for ultrasensitive electrical detection of nucleic acids. Nano Lett 11:3974–3978
Gao A et al (2012) Enhanced sensing of nucleic acids with silicon nanowire field effect transistor biosensors. Nano Lett 12:5262–5268
Gao A, Lu N, Wang Y, Li T (2016) Robust ultrasensitive tunneling-FET biosensor for point-of-care diagnostics. Sci Rep 6:22554
Hahm J-I, Lieber CM (2004) Direct ultrasensitive electrical detection of DNA and DNA sequence variations using nanowire nanosensors. Nano Lett 4:51–54
Janissen R et al (2017) InP nanowire biosensor with tailored biofunctionalization: ultrasensitive and highly selective disease biomarker detection. Nano Lett 17:5938–5949
Kim KS, Lee H-S, Yang J-A, Jo M-H, Hahn SK (2009) The fabrication, characterization and application of aptamer-functionalized Si-nanowire FET biosensors. Nanotechnology 20:235501
Kulkarni GS, Zhong Z (2012) Detection beyond the Debye screening length in a high-frequency nanoelectronic biosensor. Nano Lett 12:719–723
Laborde C, Pittino F, Verhoeven HA, Lemay SG, Selmi L, Jongsma MA, Widdershoven FP (2015) Real-time imaging of microparticles and living cells with CMOS nanocapacitor arrays. Nat Nanotechnol 10:791–795
Ladd J, Taylor AD, Piliarik M, Homola J, Jiang S (2009) Label-free detection of cancer biomarker candidates using surface plasmon resonance imaging. Anal Bioanal Chem 393:1157–1163
Lee M, Lucero AT, Kim J (2012) One-dimensional nanomaterials for field effect transistor (FET) type biosensor applications. Trans Electr Electron Mater 13:165–170
Li Z, Chen Y, Li X, Kamins TI, Nauka K, Williams RS (2004) Sequence-specific label-free DNA sensors based on silicon nanowires. Nano Lett 4:245–247
Li BR, Hsieh YJ, Chen YX, Chung YT, Pan CY, Chen YT (2013) An ultrasensitive nanowire-transistor biosensor for detecting dopamine release from living pc12 cells under hypoxic stimulation. J Am Chem Soc 135:16034–16037
Lin C-H, Hung C-H, Hsiao C-Y, Lin H-C, Ko F-H, Yang Y-S (2009) Poly-silicon nanowire field-effect transistor for ultrasensitive and label-free detection of pathogenic avian influenza DNA. Biosens Bioelectron 24:3019–3024
Lockhart DJ, Winzeler EA (2000) Genomics, gene expression and DNA arrays. Nature 405:827–836
Lu N, Dai P, Gao A, Valiaho J, Kallio P, Wang Y, Li T (2014) Label-free and rapid electrical detection of hTSH with CMOS-compatible silicon nanowire transistor arrays. ACS Appl Mater Interfaces 6:20378–20384
Luo X, Lee I, Huang J, Yun M, Cui XT (2011) Ultrasensitive protein detection using an aptamer-functionalized single polyaniline nanowire. Chem Commun 47:6368–6370
Mahdavi M, Samaeian A, Hajmirzaheydarali M, Shahmohammadi M, Mohajerzadeh S, Malboobi MA (2014) Label-free detection of DNA hybridization using a porous poly-Si ion-sensitive field effect transistor. RSC Adv 4:36854–36863
Matsumoto A, Miyahara Y (2013) Current and emerging challenges of field effect transistor based bio-sensing. Nanoscale 5:10702–10718
Mehrotra P (2016) Biosensors and their applications – a review. J Oral Biol Craniofac Res 6:153–159
Nair PR, Alam MA (2006) Performance limits of nanobiosensors. Appl Phys Lett 88:233120
Nair PR, Alam MA (2007) Dimensionally frustrated diffusion towards fractal adsorbers. Phys Rev Lett 99:256101
Park K-Y, Choi S-B, Lee M, Sohn B-K, Choi S-Y (2002) ISFET glucose sensor system with fast recovery characteristics by employing electrolysis. Sensors Actuators B Chem 83:90–97
Poghossian A, Schöning MJ, Schroth P, Simonis A, Lüth H (2001) An ISFET-based penicillin sensor with high sensitivity, low detection limit and long lifetime. Sensors Actuators B Chem 76:519–526
Proteomics market outlook (2019) https://www.alliedmarketresearch.com/proteomics-market
Rajan NK, Routenberg DA, Chen J, Reed MA (2010) 1/f noise of silicon nanowire BioFETs. IEEE Electron Device Lett 31:615–617
Rajan NK, Brower K, Duan X, Reed MA (2014) Limit of detection of field effect transistor biosensors: effects of surface modification and size dependence. Appl Phys Lett 104:084106
Rani D, Pachauri V, Madaboosi N, Jolly P, Vu X-T, Estrela P, Chu V, Conde JP, Ingebrandt S (2018) Top-down fabricated silicon nanowire arrays for field-effect detection of prostate-specific antigen. ACS Omega 3:8471–8482
Rollo S, Rani D, Leturcq R, Olthuis W, Pascual García C (2019) High aspect ratio fin-ion sensitive field effect transistor: compromises toward better electrochemical biosensing. Nano Lett 19:2879–2887
Rollo S, Rani D, Olthuis W, Pascual García C (n.d.) High performance fin-FET electrochemical sensors with high-K dielectric materials. Recently submitted to Sensors and Actuators, archiv 1907.11022
Rothberg JM et al (2011) An integrated semiconductor device enabling non-optical genome sequencing. Nature 475:348
Sakata T, Kamahori M, Miyahara Y (2005) DNA analysis chip based on field-effect transistors. Jpn J Appl Phys 44:2854–2859
Sarkar D, Liu W, Xie X, Anselmo AC, Mitragotri S, Banerjee K (2014) MoS2 field-effect transistor for next-generation label-free biosensors. ACS Nano 8:3992–4003
Schenck JF (1980) Inventor field effect transistor for detection of biological reactions. US Pat no 4,238,757
Shin J-K, Kim D-S, Park H-J, Lim G (2004) Detection of DNA and protein molecules using an FET-type biosensor with gold as a gate metal. Electroanalysis 16:1912–1918
Soldatkin AP, Montoriol J, Sant W, Martelet C, Jaffrezic-Renault N (2003) A novel urea sensitive biosensor with extended dynamic range based on recombinant urease and ISFETs. Biosens Bioelectron 19:131–135
Stern E et al (2010) Label-free biomarker detection from whole blood. Nat Nanotechnol 5:138–142
Tabata M, Goda T, Matsumoto A, Miyahara Y (2016) Field-effect transistors for detection of biomolecular recognition. In: Sone JI, Tsuji S (eds) Intelligent Nanosystems for Energy, Information and Biological Technologies. Springer Japan, Tokyo, pp 13–25
Tian R, Regonda S, Gao J, Liu Y, Hu W (2011) Ultrasensitive protein detection using lithographically defined Si multi-nanowire field effect transistors. Lab Chip 11:1952–1961
Uno T, Tabata H, Kawai T (2007) Peptide−nucleic acid-modified ion-sensitive field-effect transistor-based biosensor for direct detection of DNA hybridization. Anal Chem 79:52–59
Van Hal REG, Eijkel JCT, Bergveld P (1996) A general model to describe the electrostatic potential at the electrolyte oxide interface. Adv Colloid Interf Sci 69:31–62
Whirl-Carrillo M et al (2012) Pharmacogenomics knowledge for personalized medicine. Clin Pharmacol Ther 92:414–417
Xi B, Yu N, Wang X, Xu X, Abassi Y (2008) The application of cell-based label-free technology in drug discovery. Biotechnol J 3:484–495
Xu G, Abbott J, Ham D (2016) Optimization of CMOS-ISFET-based biomolecular sensing: analysis and demonstration in DNA detection. IEEE Trans Electron Devices 63:3249–3256
Zafar S et al (2018) Silicon nanowire field effect transistor sensors with minimal sensor-to-sensor variations and enhanced sensing characteristics. ACS Nano 12:6577–6587
Zayats M, Huang Y, Gill R, Ma C-a, Willner I (2006) Label-free and reagentless aptamer-based sensors for small molecules. J Am Chem Soc 128:13666–13667
Zhang Y, Chen R, Xu L, Ning Y, Xie S, Zhang G-J (2015) Silicon nanowire biosensor for highly sensitive and multiplexed detection of oral squamous cell carcinoma biomarkers in saliva. Anal Sci 31:73–78
Zheng G, Patolsky F, Cui Y, Wang WU, Lieber CM (2005) Multiplexed electrical detection of cancer markers with nanowire sensor arrays. Nat Biotechnol 23:1294–1301
Zheng G, Gao XPA, Lieber CM (2010) Frequency domain detection of biomolecules using silicon nanowire biosensors. Nano Lett 10:3179–3183
Acknowledgments
We would like to thank Sivashankar Krishnamoorthy for the useful discussions and help during the project.
Funding
This project was financed by the FNR under the Attract program, fellowship number 5718158 NANOpH.
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Rollo, S., Rani, D., Olthuis, W. et al. The influence of geometry and other fundamental challenges for bio-sensing with field effect transistors. Biophys Rev 11, 757–763 (2019). https://doi.org/10.1007/s12551-019-00592-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12551-019-00592-5