Ionic Transport Through Nanopores: From Living Cells to Ionic Diodes and Transistors

1. Ionic Transport Through Nanopores: From Living Cells to Ionic Diodes and Transistors Zuzanna S. SiwyDepartment of Physics and AstronomyUniversity of California, Irvine

2. Main Object of Our Studies Our main object of studies is a single nanopore in a polymer film - + 12 mm Several nanometers, typically 2-6 nm ~ 1 mm We study ionic transport through single conical nanopores

3. polymer foil heavy ion Outline • Motivation for studies of single nanopores • Fabrication of single nanopores by the track-etching technique. • Motivation for studying conically shaped nanopores. • Preparation of ionic devices controlling transport of ions in water solutions: • Preparation of ionic unipolar rectifiers. • Preparation of an ionic bipolar diode and transistor (BJT); similarities and differences to semiconductor devices. • On the way to make a field effect transistor for ions. • Ionic diodes as biosensors. 5. Nanoprecipitation in nanopores and electrochemical oscillations. 6. Conclusions.

4. Lessons from Nature Transport Proteins are Nature’s Nanotubes Impermeable lipid bilayer membrane Membrane-Bound Transport Proteins Allow for highly selective transport of ions, sugars, amino acids, etc. across the lipid bilayer membrane

5. Biological Pores are Smart “Holes” – Very Selective Transport of Millions of Ions per 1 s A potassium selective channel is a very important player in the nerve signaling. < 1 nm Potassium selective channel with four K+ in the selectivity filter (right panel). R. MacKinnon, P. Agre 2003 E. Gouaux, R. MacKinnon, Science310, 1461 (2005).S. Berneche, B.Roux, Nature 414, 73 (2001).

6. Selectivity of L-Type Calcium Channels (Heart Muscle Regulation) Negative groups COO- E.W. McCleskey, J. Gen. Physiol.113, 765 (1999) [Ca2+] << [Na+] Ca2+ and Na+ have basically the same diameter. W. Nonner, D. Gillespie, D. Henderson, B. Eisenberg, J. Phys. Chem. 105, 6427 (2001);

7. PHYSICS approach COO- COO- COO- COO- ~1 e/nm2 e = electron charge COO- = carboxyl group with charge -e COO- COO- COO- COO- COO- ~1 e/nm2 Preparation of the Simplest Calcium Channel/Pore Theoretical predictions: highly charged lining of the pore and small pore volume lead to Ca2+ selectivity. Our synthetic analogue (a synthetic hole) is indeed Ca2+ selective! Gillespie, D., Boda, D., He Y. Apel, P., Siwy, Z.S. (2008) Synthetic Nanopores as a Test Case for Ion Channel Theories: The Anomalous Mole Fraction Effect. Biophysical Journal95, 609-619.

8. PHYSICS approach What are the Physical Requirements for Making Ionic Diodes and Transistors? Perhaps a Basis for Ionic Electronics? Diode - Like Characteristics of Biological Channels A diode perfectly rectifies currents so that it flows in one direction I [pA] rectifier V [mV] diode Y. Jiang et al. Nature 417, 515 (2002) T. Baukrowitz et al. EMBO 18, 847 (1999) Many biological channels are switches for ions

9. _ _ _ _ _ _ _ _ _ _ + + + + + + + + + + _ _ _ _ _ _ _ _ + + + + + + + + + Nanopores – Studying Interactions at the Nanoscale Nanopores have very large surface! Nanopores give a unique possibility to control transport of ions and charged molecules in water-based solutions.

10. Nanopores as Basis for Biosensors Sub-femtoliter volume! Very few molecules actually fit there! Basis for single molecule detection!

11. I Will Talk About.. • Preparation of various components of IONICCIRCUITS for ions and molecules in a water solution: urgent need for systems that operate in water. • For that we need: TEMPLATE - robust single nanopores with tunable geometry and surface chemistry i.e. tunable electrochemical potential.

12. Outline polymer foil heavy ion • Motivation for studies of single nanopores. • Fabrication of single nanopores by the track-etching technique. • Motivation for studying conically shaped nanopores. • Preparation of ionic devices controlling transport of ions in water solutions: • Preparation of ionic unipolar rectifiers. • Preparation of an ionic bipolar diode and transistor (BJT); similarities and differences to semiconductor devices. • On the way to make a field effect transistor for ions. • Ionic diodes as biosensors. 5. Nanoprecipitation in nanopores and electrochemical oscillations. 6. Conclusions.

13. Heavy Ions as a Working Tool 1. Irradiation with e.g. Xe, Au, U (~2.2 GeV i.e. ~ 15% c) Latent tracks E. Loriot Linear accelerator UNILAC, GSI Darmstadt, Germany 2. Chemical etching 1 ion  1 latent track  1 pore ! R.L. Fleischer, P.B. Price, R.M. Walker (1975)

14. Heavy Ions as a Working Tool 1. Irradiation with e.g. Xe, Au, U (~2.2 GeV i.e. ~ 15% c) E. Loriot Linear accelerator UNILAC, GSI Darmstadt, Germany 2. Chemical etching 1 ion  1 latent track  1 pore ! R.L. Fleischer, P.B. Price, R.M. Walker (1975)

15. Tuning the Pore Shape during Etching Vb Vt Vb – Rate of non-specific etching the so-called bulk etching Vt - Rate of etching along the latent track Recipes for cylindrical and conical nanopores: Cylindrical pores: high Vt and low Vb; for PET 0.5 M NaOH in 70 ºCConical pores: low Vtand high Vb; for PET 9 M NaOH, RT

16. Example for 0.5 V, 1 M KCl, L = 10mm d=1 nm results in current of 3.9 pA. d=1 nm, D=2 mm, results in current of ~740 pA. Why Do We Want to Work with Asymmetric Pores? Tapered cone Cylindrical pore D L d d >>

17. Conical Pores are Obtained by Putting Etch Solution on One Side of Membrane and Stop Solution of the Other I Single ion irradiation U Current (pA) acidic solution NaOH time (min) Z. Siwy et al. Nucl. Instr. Meth. B208, 143-148 (2003); Applied Physics A76, 781-785; Surface Science532-535, 1061-1066 (2003).

18. ~ 2 – 10 nm Gold Replica of a Single Conical Pore P. Scopece et al. Nanotechnology 17, 3951 (2006)

19. Anode Cathode Electro-Stopping Technique to Prepare Double-Conical Pores For polyethylene terephthalate Etch solution 9 M NaOH Etch solution 9 M NaOH

20. Cross – Section of Membranes with Double-Conical Nanopores P. Apel, Dubna

21. Hydrolysis of Ester Bonds with NaOH in PET Causes Formation of COOH Groups OH- The surface density of COOH groups was estimated to be ~ 1.0 per nm2 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _

22. Outline polymer foil heavy ion • Motivation for studies of single nanopores • Fabrication of single nanopores by the track-etching technique. • Motivation for studying conically shaped nanopores. • Preparation of ionic devices controlling transport of ions in water solutions: • Preparation of ionic unipolar rectifiers. • Preparation of an ionic bipolar diode and transistor (BJT); similarities and differences to semiconductor devices. • On the way to make a field effect transistor for ions. • Ionic diodes as biosensors. 5. Nanoprecipitation in nanopores and electrochemical oscillations. 6. Conclusions.

23. I U 0.1 M KCl 0.1 M KCl Transport Properties of Conical Nanopores

24. COOH COO- Single Conical Nanopores Rectify Ion Current Current (nA) 0.1 M KCl, pH 3 Voltage (mV) Vb - Vt 0.1 M KCl, pH 8 Vb Vt ~ 3 nm ~ 600 nm Z. Siwy et al. Europhys. Lett. 60, 349 (2002); Z. Siwy et al. Surface Science 532-535, 1061 (2003)

25. I U Which Ions Are Transported? PET and Kapton pores are selective for positive ions (cations) t+ ~ 0.80 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ Z. Siwy, A Fulinski, Phys. Rev. Lett. 89, 198103 (2002); Am. J. Phys. 72, 567 (2004).Siwy Z., Adv. Funct. Mat.16, 735 (2006). UNIPOLAR DEVICE – mainly pass through

26. Why do Asymmetric and Charged Pores Rectify The profile of electric potential V(z) of a cation in an asymmetric nanopore z Siwy Z., Fulinski A. Phys. Rev. Lett.89, 198103 (2002); Siwy Z., Fulinski A. The American Journal of Physics 74 (2004) 567; Siwy Z., Adv. Funct. Mat.16, 735 (2006). Cervera, J., Schiedt, B., Ramirez, P. Europhys. Lett.71, 35-41 (2005).

27. PROBLEM: Degree of Rectification of Conical Nanopores I(nA) 1 -3 3 U(V) -2 -4 Ideally, from application stand point one wants a SWITCH i.e. basically zero leakage current.

28. Depletion zone How to Make an Ionic Switch? _ _ _ _ _ _ _ _ _ _ + + + + + + + + + + _ _ _ _ _ _ _ _ + + + + + + + + + H. Daiguji, P. Yang, A. Majumdar, NanoLett., 4, 137 (2005). I. Vlassiouk, Z.S. Siwy, Nano Lett. 7, 553 (2007)

29. HIGH Conductance State of Nanopore Eric Kalman _ _ _ _ _ _ _ _ _ _ + + + + + + + + + + _ _ _ _ _ _ _ _ + + + + + + + + + BIPOLAR DEVICE – current carried by both

30. Targeted Modification of the Tip GOAL! , The negative groups (COO-) at the narrow opening have to be changed into groups with positive charges, e.g. NH3+

31. C0 CL=0 Steady-State Solution of Diffusion Problem x Distribution of concentration of a reagent introduced only on the tip side of the membrane Targeted modification of the tip Only the region of the pore close to the tip with high enough EDC and amines concentration will be modified!

32. Ethylenediamine + EDC Succinide anhydride + EDC _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ Modification Chemistry Ethylene diamine + EDC, 0.1 M KCl, pH 5.5 0.1 M KCl, pH 5.5

33. An Ionic Diode Made From a Nanopore with a Positive Tip 0.1 M KCl, pH 5.5 I. Vlassiouk, Z.S. Siwy, Nano Lett. 7, 553 (2007)

34. Positively Charged Nanopore + + + + + + + + + + + + + + + + + + 0.1 M KCl, pH 5.5

35. An Ionic Diode Made From a Nanopore with a Negative Tip 0.1 M KCl, pH 5.5 I. Vlassiouk, Z.S. Siwy, Nano Lett. 7, 553 (2007)

36. Tuning Rectification We can measure ion rectification degree in situ during the modification! I. Vlassiouk, Z.S. Siwy, Nano Lett. 7, 553 (2007)

37. Diode Pattern Realized in a Bacterial Biopore WITHOUTcharges WITH charges Miedema, H.; Vrouenraets, M.; Wierenga, J.; Meijberg, W.; Robillard, G.; Eisenberg, B. A Biological Porin Engineered into a Molecular, Nanofluidic Diode. Nano Letters 7 (2007) 2886-2891.

38. Unipolar Diodes Were Also Prepared 10 mM KCl Voltage (V) R. Karnik, C. Duan, K. Castelino, H. Daiguji, A. Majumdar Nano Letters 7,547-551 (2007). I. Vlassiouk, S. Smirnov, Z. Siwy, ACS Nano2, 1589 (2008)

39. Poisson-Nernst-Planck Modeling of Ionic Diodes Ci– concentration of positive and negative ions - electric potential - dielectric constantJi– flux of an ion i with charge zi Density of charge carriers is described by the Boltzmann statistics

40. A Semiconductor Diode Vs an Ionic Diode 1 mm long, 0.5 e/nm2, 0.1 M KCl holes (+) electrons (-) p-doped n-doped Carrier concentration Voltage Numerical solutions of PNP

41. Current Current Voltage Voltage N.W. Ashcroft, N.D. Mermin, Solid State Physics, Thomas Learning, 1976 I. Vlassiouk, S. Smirnov, Z. Siwy, ACS Nano2, 1589 (2008) 1-D Analytical Approximations for Diodes Depletion zone a – pore radius - surface charge density doping

42. Depletion Zone in LONG Pores _ _ _ _ _ _ _ _ _ _ + + + + + + + + + + _ _ _ _ _ _ _ _ + + + + + + + + + Depletion zone I. Vlassiouk, S. Smirnov, ACS Nano2, 1589 (2008)

43. Depletion Zone in SHORT Pores _ _ _ _ _ _ _ _ _ _ + + + + + + + + + + _ _ _ _ _ _ _ _ + + + + + + + + + The depletion zone fills the whole pore, which can be treated as a neutral pore I. Vlassiouk, S. Smirnov, ACS Nano2, 1589 (2008)

44. Opening of Short Diodes (V) Cbulk = 0.1 M KCl, charge density 0.5 e/nm2, radius 4 nm

45. + + + + + + + + + + + + Cl- K+ Cl- + + + + + + + + + + + + Preparation of Ionic Bipolar Junction: Transistor I V diode P-N junctions P. Apel, Dubna

46. Step-by-Step Modifications E. Kalman, I. Vlassiouk, Z. Siwy, Advanced Materials20, 293 (2008).

47. Performance of Ionic BJT + + + + _ _ + + _ 0.5 M KCl 0.5 M KCl _ _ _ _ + + + + + Salt concentration determines the potential in the pore and thus the leakage current level in BJT

48. “+ 0 +” junction “0 - 0” Performance of Ionic BJT – pH response “+ - +” junction E. Kalman, I. Vlassiouk, Z. Siwy, Advanced Materials20, 293 (2008).

49. Ti Adhesion Layers SiO2 Insulating Layer Au Gate Electrode 12 mm PET Membrane Not to scale Ionic Gated Channel with Electrically Addressable Gate – On the Way to Make FET

50. Gated Conical Nanopore 0 V -1.0 V Applying negative gate voltage to the gate causes suppression of ion currents