title: Single-chip microelectronic system to interface with living cells.
abstract: A high degree of connectivity and the coordinated electrical activity of neural cells or networks are believed to be the reason that the brain is capable of highly sophisticated information processing. Likewise, the effectiveness of an animal heart largely depends on such coordinated cell activity. To advance our understanding of these complex biological systems, high spatiotemporal-resolution techniques to monitor the cell electrical activity and an ideally seamless interaction between cells and recording devices are desired. Here we present a monolithic microsystem in complementary metal oxide semiconductor (CMOS) technology that provides bidirectional communication (stimulation and recording) between standard electronics technology and cultured electrogenic cells. The microchip can be directly used as a substrate for cell culturing, it features circuitry units per electrode for stimulation and immediate cell signal treatment, and it provides on-chip signal transformation as well as a digital interface so that a very fast, almost real-time interaction (2 ms loop time from event recognition to, e.g., a defined stimulation) is possible at remarkable signal quality. The corresponding spontaneous and stimulated electrical activity recordings with neuronal and cardiac cell cultures will be presented. The system can be used to, e.g., study the development of neural networks, reveal the effects of neuronal plasticity and study cellular or network activity in response to pharmacological treatments.
authors.affiliation: Physical Electronics Laboratory, ETH Zürich, ETH Hönggerberg, HPT H 4.2, Wolfgang-Pauli-Strasse 16, CH-8093 Zurich, Switzerland. fheer@phys.ethz.ch <fheer@phys.ethz.ch>
authors.forename: F
authors.initials: F
authors.lastname: Heer
authors.forename: S
authors.initials: S
authors.lastname: Hafizovic
authors.forename: T
authors.initials: T
authors.lastname: Ugniwenko
authors.forename: U
authors.initials: U
authors.lastname: Frey
authors.forename: W
authors.initials: W
authors.lastname: Franks
authors.forename: E
authors.initials: E
authors.lastname: Perriard
authors.forename: J-C
authors.initials: JC
authors.lastname: Perriard
authors.forename: A
authors.initials: A
authors.lastname: Blau
authors.forename: C
authors.initials: C
authors.lastname: Ziegler
authors.forename: A
authors.initials: A
authors.lastname: Hierlemann
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000669:Amplifiers, Electronic; D000818:Animals; D002478:Cells, Cultured; D002645:Chickens; D004558:Electric Stimulation / Q000295:instrumentation* / Q000379:methods; D004867:Equipment Design; D019544:Equipment Failure Analysis; D008839:Microelectrodes; D008904:Miniaturization; D032383:Myocytes, Cardiac / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000295:instrumentation*; D051381:Rats; D014173:Transistors, Electronic