FluidFM technology: from single-cell manipulation to nanoparticle lithography Tomaso Zambelli Laboratory of Biosensors and Bioelectronics Institute for Biomedical Engineering D-ITET www.lbb.ethz.ch 1 force-controlled patch clamp? PhD M. Gabi (Oct 2006) inspiration Laboratory of Biosensors and Bioelectronics → patch-clamp technique* → only optical control → hit-and-miss objective development of a microinjector with force feedback screening cascade to be operated in liquid environment (GABA receptors) challenge combining nanofluidics and atomic force microscopy (AFM) * E. Neher and B. Sakmann, 1991 Nobel Laureates in Medicine Neher et al, Nature 260 (1976) 799 Hamill et al, Pflügers Arch 391 (1981) 85 2 hollow AFM cantilevers Nanoscale dispensing of liquids Fountain pen nanochemistry: Atomic force control of chrome etching through cantilevered probes Meister et al, Microel Eng 67–68 (2003) 644 → NADIS Lewis et al, Appl Phys Lett 75 (1999) 2689 Meister et al, Appl Phys Lett 85 (2004) 6260 Meister et al, NSTI-Nanotech 2008 v3, p273 [Hug et al, Dig Tech Pap Transducers ′05 2 (2005) 1191] in air! Neuchâtel (CH) capillarity Micromachined fountain pen for AFM-based nanopatterning A Nanofountain Probe with Sub-100 nm Deladi et al, Appl Phys Lett 85 (2004) 5361 Molecular Writing Resolution Loh et al, Small 1 (2005) 632 volcano tips Loh et al, Small 5 (2009) 1667 with cells but removing the buffer 3 FluidFM: concept PhDs M. Gabi, P. Behr JPK AFM Nanowizard I together with Neuchâtel (CH) buffer glass slide Nano Lett 9 (2009) 2501 4 micro- nanoinjectors nanotube endoscope glass micropipette Singhal et al, Barber, Nat Nanotech 6 (2011) 57 J Kansas Med Sot 4 (1904) 489 FluidFM pyramidal tip Nano Lett 9 (2009) 2501 1 µm 5 perforation vs. gentle contact 4 * perforation ) N n (2 e c r gentle contact o F 0 * 200 nm FIB → J. Bitterli 200 nm (PhD, CSEM) Nano Lett 9 (2009) 2501 6 spatial manipulation PhDs P. Dörig, P. Stiefel z z Prof. Vorholt (IMB ETH D-BIOL) budding yeasts 1 2 x z y 3 4 [pN, µN] spread neurons 30 µm Appl Phys Lett 97 (2010) 023701 7 FluidFM Commercialization Research www.cytosurge.com (Dr. M.Gabi and P.Behr) Electrophysiology Biology Biosensing Engineering coll. Prof. H.Abriel coll. Prof. J.A.Vorholt Lithography Skeleton SICM Infection coll. Dr. J.Mercer Chemistry SU-8 Patch clamp Adhesion Electrochemistry Self-Sensing Ion mapping (ISE) coll. Dr. Polesel Maris Injection Nano-optics Neuron stimulation (MEA) Omics analysis MultiProbe (extraction)  beyond the proof-of-concept!  try to answer or stimulate an original question… 8 FluidFM probes Dr. Edin Sarajlic SmartTip & Cytosurge Deladi et al, Appl Phys Lett 85 (2004) 5361 Berenschot et al, Small 8 (2012) 3823 down to 50 nm down to 2 µm 10 µm 9 the wrath Μῆνιν ἄειδε θεὰ Πηληϊάδεω Ἀχιλῆος οὐλομένην… (Homer, Iliad I:1-2) AFM probes  F(z)  k  stability  aperture  electrodes  Au layer results complementary scientific instrumentation questions  pressure controller  optical microscope  patch clamp electronics  … 10