Biologically sensi-ve field- effect transistors: Part 1 (measuring Ions and biochemical species)

Transcription

1 Biologically sensi-ve field- effect transistors: Part 1 (measuring Ions and biochemical species) Henrique Leonel Gomes Universidade do Algarve, FCT, Campus de Gambelas, 8000 Faro, Portugal (hgomes@ualg.pt) 1

2 Sources used for this lesson This lesson is based on the work of several research groups namely the works of: Michael J. Schöninga and Arshak Poghossianb, Analyst, 2002, 127, Sungho Kim, et al. J. Appl. Phys. 107, Maesoon Im and Yang- Kyu Choi, nature nanotechnology, VOL 2, JULY A lesson by José Antonio Garrido, Biosensors & Bioelectronics I (2008/2009). Paul C. McIntyre,Department of Materials Science & Engineering, Geballe Laboratory for Advanced Materials, Stanford University (nanowires FET sensors) 2

3 Outline 1 Introduccon 2 BioFETs in general Biosensor definicon and nomenclature BioFET principle 3 Classificacon and advances in BioFETs EnFET ImmunoFET GenFET 4. A dielectric- modulated field- effect transistor 5. Nanogap- Embedded Separated Double- Gate 6. Nanowires FET sensors 7. Summary 3

4 Learning outcomes Aher this lesson the student should be able to: Understand how a MOSFET type of device can be used to detect bio- chemical species. Parccular how charges stored in the vicinity of the insulator affect the band alignment of the MOS structure. Know effects of charge neutralizacon by surrounding charges and the debate about the deteccng ability of these type of devices. Know the different design strategies to fabricate transistors sensicve to biochemicals, namely the use of nanogaps and nanowires. 4

5 BioFET principle Fig.1. Structure of an ISFET. RE, reference electrode; VG, gate voltage; VDS, drain- source voltage; ID, drain current. Source: Michael J. Schöning and Arshak Poghossianb Analyst, 2002, 127,

6 Ion- sensi-ve Field effect transistor Source: Michael J. Schöning and Arshak Poghossianb Analyst, 2002, 127,

7 Ion- sensi-ve Field effect transistor Source: Michael J. Schöning,Sensors 2005, 5,

8 Ion- sensi-ve Field effect transistor Source: Michael J. Schöning,Sensors 2005, 5,

9 BioFET Classifica-on BioFETs can be classified according to the biorecognicon element that is used for Deteccon. Diagram of possible BioFET classificacon. Source: Michael J. Schöning and Arshak Poghossianb Analyst, 2002, 127,

10 A bit of history The following Table summarises major historical landmarks in the development of the different types of BioFETs Concept of an ISFET, first alempt to apply the ISFET in neurophysiological measurements 1976 Concept of the first BioFET (EnFET) 1980 First realised EnFET Concept of an ImmunoFET Coupling cells with a MOSFET First neuron- transistor (or CPFET) Beetle/chip BioFET First experimental alempt of direct DNA hybridisacon deteccon Source: Michael J. Schöning and Arshak Poghossianb Analyst, 2002, 127,

11 Why transistors are so popular? The reason why silicon- based field effect devices are being the basic structural element in a new generacon of micro biosensor is because they provide several potencal advantages such as: Small size and weight, fast response, high reliability, low output impedance. The possibility of automacc packaging at wafer level, on- chip integracon of biosensor arrays and a signal processing scheme with the future prospect of low- cost mass produccon of portable microanalysis systems. Their possible field of applicacons reaches from medicine, biotechnology and environmental monitoring through food and drug industries to defence and security. 11

12 Basics about the opera-on of MOSFETs - Drain Gate Insulator Source Source: Christopher Byrd, University of Maryland, College Park hlp:// 12

13 Basics about the opera-on of MOSFETs + - Drain Gate Insulator Source (Not conductive enough) (Electron Channel) Source: Christopher Byrd, University of Maryland, College Park hlp:// 13

14 Basics about the opera-on of MOSFETs + Drain Threshold Voltage Gate Insulator - Source Source: Christopher Byrd, University of Maryland, College Park hlp:// 14

15 Basics about the opera-on of MOSFETs + - Drain - Gate Insulator Source Source: Christopher Byrd, University of Maryland, College Park hlp:// 15

16 MOSFETs vs ISFETs Source: Development of an Ion- Sensicve Solid- State Device for Neurophysiological Measurements, P. Bergveld IEEE Trans. On Biomedical Engin.,

17 Ideal Metal- Oxide- Semiconductor junc-on The Ideal MOS structure 17

18 Metal- Oxide- Semiconductor junc-on Source: José Antonio Garrido, Biosensors & Bioelectronics I (2008/2009) 18

19 Metal- Oxide- Semiconductor junc-on Source: José Antonio Garrido, Biosensors & Bioelectronics I (2008/2009) 19

20 Metal- Oxide- Semiconductor junc-on Source: José Antonio Garrido, Biosensors & Bioelectronics I (2008/2009) 20

21 Electrolyte/Oxide Interface Source: José Antonio Garrido, Biosensors & Bioelectronics I (2008/2009) 21

22 Electrolyte/Oxide/Semiconductor System Source: José Antonio Garrido, Biosensors & Bioelectronics I (2008/2009) 22

23 Principle of func-on of a penicillin- The enzyme penicillinase catalyses the hydrolysis of penicillin to penicilloic acid yielding a local ph change near the gate region of the ISFET. Then, the output signal change will be determined by the amount of penicillin in the sample solucon. Such an EnFET can be constructed, in principle, with any kind of enzyme. sensi-ve EnFET Structure and principle of funccon of a penicillin- sensicve EnFET (PenFET). The enzyme penicillinase is immobilised on top of a ph- sensicve ISFET with Ta2O5 as ph- sensicve gate insulator. Source: Michael J. Schöning and Arshak Poghossianb Analyst, 2002, 127,

24 Theore-cal Model Source: Michael J. Schöning and Arshak Poghossianb Analyst, 2002, 127,

25 Enzyme system used and the analyte to be detected Source: Michael J. Schöning and Arshak Poghossianb Analyst, 2002, 127,

26 Limita-ons of EnFETs Problems preven-ng commercial development of EnFETs: (i) (ii) The dependence of the sensor response on buffer capacity, ionic strength and ph of the test sample. The higher value of deteccon limit, restricted dynamic range and non- linearity. (iii) The relacvely slow response and recovery cmes. (iv) The operacng and storage stability, the light sensicvity as well as reproducibility. (v) The dependence on enzyme immobilisacon and deposicon methods. (vi) The incompacbility of most used enzyme containing layer deposicon and palerning methods with silicon integrated circuit technology. 26

27 ph ISFET/EnFET differen-al arrangement ph ISFET/EnFET differencal arrangement. The ph ISFET acts as reference system; it is buit- up in the same way as the EnFET but without immobilised enzyme membrane. Source: Michael J. Schöning and Arshak Poghossianb Analyst, 2002, 127,

28 ImmunoFET Schemacc structure of an ImmunoFET with immobilised ancbody (Ab) molecules. Ag, ancgen molecules. Ancbodies and ancgens (or more generally, proteins) are mostly electrically charged molecules. Te formacon of an ancbody ancgen complex on the gate of an ISFET would lead to a detectable change in the charge distribucon and thus, directly modulate the drain current of the ISFET. Many research efforts have been expended to realise this idea, however, the results obtained were unsacsfactory due to fundamental limitacons Source: Michael J. Schöning and Arshak Poghossianb Analyst, 2002, 127,

29 Poten-al distribu-on in an electrolyte/immunofet structure The potencal (charge) distribucon in the immediate vicinity of the interface plays a criccal role in transferring an immunological signal to the ISFET. It can be seen that only potencal (or charge density) changes which occur within the order of the Debye length d can be detected. Coupling of proteins to the surface of an ISFET within this distance has not been, however, a realiscc possibility so far.148 Dimensions of macromolecules, like ancbodies, are much longer (ca. 10 nm) than those of the double layer (ca. 1 nm in a physiological- type solucon) at the electrolyte insulator interface. As a consequence, in such a case the protein charge will be at a distance greater from the surface than the Debye length [Fig. 7(a)] and thus, will be shielded by counter ions. The certain overlapping of potencals [Fig. 7(b)], consequently a measurable effect with an ImmunoFET can only be obtained in solucons with low ionic strength ( < M). Schemacc presentacon of the potencal distribucon in an electrolyte/immunofet structure as a funccon of the distance from the gate- insulator surface by high (a) and low (b) ionic strength. d, Debye length; dab, dimension of macromolecule (e.g., ancbody). Source: Michael J. Schöning and Arshak Poghossianb Analyst, 2002, 127,

30 Are ImmunoFET structure really working? Nowadays, it is generally accepted that screening of protein charges by small inorganic counter ions present in the solucon results in macroscopically uncharged layers and prevents successful measurements of immunospecies. 30

31 GenFET Schemacc structure of a DNA- FET (GenFET) and the principle of DNA- hybridisacon deteccon. There are scll insufficient experimental results on the basis of GenFETs for clearly understand their funcconing. Source: Michael J. Schöning and Arshak Poghossianb Analyst, 2002, 127,

32 GenFET The response of a GenFET to successive addicons of poly(da). A direct dependence on the quancty of poly(da) added was achieved. There are discussion that transistor - based genosensors are not sufficiently sensicve enough to detect hybridisacon events. Source: Michael J. Schöning and Arshak Poghossianb Analyst, 2002, 127,

33 Summary of developed (bio- )chemical sensors: EIS, LAPS, ISFET. Source: Michael J. Schöning,Sensors 2005, 5,

34 A dielectric- modulated field- effect transistor Three- dimensional structure showing the silicon body (blue), the gate oxide (green) and the chromium (orange) and gold (yellow) electrodes. The narrow region of the silicon body forms the accve silicon region (the channel). The chromium layer is parcally etched to form an air gap that can be filled with biomolecules Source: 34

35 A dielectric- modulated field- effect transistor Source: Maesoon Im and Yang- Kyu Choi, nature nanotechnology, VOL 2, JULY

36 A dielectric- modulated field- effect transistor Source: Maesoon Im and Yang- Kyu Choi, nature nanotechnology, VOL 2, JULY

37 A dielectric- modulated field- effect transistor Gate (before) 37

38 A dielectric- modulated field- effect transistor Gate (w/ Gate complete (after Biomolecule) etch, w/biotin) d 38

39 A dielectric- modulated field- effect transistor I DS V GS characterisccs of the DMFET nanogap device. a, Results of simula-on with low- k materials. b, Experimental results at V DS V. 39

40 A dielectric- modulated field- effect transistor Electrical characterisccs of the DMFET nanogap device before and aher biomolecules are immobilized in the nanogap. a, IGS VGS characterisccs in one device at VDS V. b, Stacsccal distribucon of IGS measured in 15 different devices with VGS. 1.5 V. c, IDS VGS characteriscc changes aher breaking the biocn streptavidin binding at VDS V. d, The threshold voltage depends on the laterally etched length of the DMFET nanogap devices. 40

41 A dielectric- modulated field- effect transistor Electrical characterisccs of the DMFET nanogap device before and aher biomolecules are immobilized in the nanogap. a, IGS VGS characterisccs in one device at VDS V. b, Stacsccal distribucon of IGS measured in 15 different devices with VGS. 1.5 V. c, IDS VGS characteriscc changes aher breaking the biocn streptavidin binding at VDS V. d, The threshold voltage depends on the laterally etched length of the DMFET nanogap devices. 41

42 A dielectric- modulated field- effect transistor Schemacc diagram of the nanogap- embedded biotransistor and the experimental setup for the charge pumping measurements. B Schemacc of the band diagram at the gate voltage of VH and c at that of VL. The shadowed area is the trap states in energy and space that will capture and hence contribute to Icp during the charge pumping measurements. Source: Sungho Kim, et al. J. Appl. Phys. 107,

43 A dielectric- modulated field- effect transistor Source: Sungho Kim, et al. J. Appl. Phys. 107,

44 A dielectric- modulated field- effect transistor Source: Sungho Kim, et al. J. Appl. Phys. 107,

45 Nanogap- Embedded Separated Double- Gate Field Effect Transistor Schemacc diagram of a nanogap- embedded separated double- gate field effect transistor (nanogap- DGFET). (b) Magnified view of the nanogap near the drain and gate 2. Doled box conceptually shows immobilized avian influenza ancgen conjugated with silica binding protein (SBP- AIa) (Gu et al., 2009) and avian influenza ancbody (anc- AI) inside the nanogap. Reprinted with permission from (Im et al., 2011) Source: Maesoon Im and Yang- Kyu Choi 45

46 Nanogap- Embedded Separated Double- Gate Field Effect Transistor Scanning electron microscopy images of the fabricated device. (a) Top view of nanogap- embedded seperated double- gate filed effect transistor. The width (W) and the length (L) of this transistor are 150 nm and 1μm, respeccvely. (b) Cross- secconal view of a nanogap in test palern. The width of nanogap is 30 nm. Source: Maesoon Im and Yang- Kyu Choi New Perspeccves in Biosensors Technology and Applicacons 46

47 Nanogap- Embedded Separated Double- Gate Field Effect Transistor Source: Maesoon Im and Yang- Kyu Choi New Perspeccves in Biosensors Technology and Applicacons 47

48 Nanowires Source: Charles M. Lieber, Harvard U. 48

49 Nanowires 49

50 Nanowires 50

51 Electrical detec-on of viruses using nanowires 51

52 Ideas for a Verccal Surround Gate Transistor with Nanowires Source: Paul C. McIntyre,Department of Materials Science & Engineering, Geballe Laboratory for Advanced Materials Stanford University 52

53 Nanowire FET Sensors Source: Paul C. McIntyre,Department of Materials Science & Engineering, Geballe Laboratory for Advanced Materials Stanford University 53

54 Silicon Nanowire Bio- FET Source: Paul C. McIntyre,Department of Materials Science & Engineering, Geballe Laboratory for Advanced Materials Stanford University 54

55 Summary Changes in the surface charge density of MIS- capacitors or MISFETs can be used for biochemical sensing. The charge on the surface of the dielectric can be rapidly neutralized by surround electrical charges, this rises some doubts about the operacon of some of the ISFETs proposed in the literature. The dielectric layer can be structural modified (nano- gaps) so the adsorpcon of species modifies the dielectric constant. Several type of nanowires that can be incorporated in transistor type of structures are emergent with promising applicacons in bi sensing. 55