Siddharth Ramakrishnan

Single Ion Channel Recordings with CMOS-Anchored Lipid Membranes

We present single-ion-channel recordings performed with biomimetic lipid membranes which are directly attached to the surface of a complementary metal-oxide-semiconductor (CMOS) preamplifier chip. With this system we resolve single-channel currents from several types of bacterial ion channels, including fluctuations of a single alamethicin channel at a bandwidth of 1 MHz which represent the fastest single-ion-channel recordings reported to date. The platform is also used for high-resolution α-hemolysin nanopore recordings. These results illustrate the high signal fidelity, fine temporal resolution, small geometry, and multiplexed integration which can be achieved by leveraging integrated semiconductor platforms for advanced ion channel interfaces.

Hybrid integrated biological–solid-state system powered with adenosine triphosphate

There is enormous potential in combining the capabilities of the biological and the solid state to create hybrid engineered systems. While there have been recent efforts to harness power from naturally occurring potentials in living systems in plants and animals to power complementary metal-oxide-semiconductor integrated circuits, here we report the first successful effort to isolate the energetics of an electrogenic ion pump in an engineered in vitro environment to power such an artificial system. An integrated circuit is powered by adenosine triphosphate through the action of Na+/K+ adenosine triphosphatases in an integrated in vitro lipid bilayer membrane. The ion pumps (active in the membrane at numbers exceeding 2 × 106 mm−2) are able to sustain a short-circuit current of 32.6 pA mm−2 and an open-circuit voltage of 78 mV, providing for a maximum power transfer of 1.27 pW mm−2 from a single bilayer. Two series-stacked bilayers provide a voltage sufficient to operate an integrated circuit with a conversion efficiency of chemical to electrical energy of 14.9%.

High-resolution extracellular stimulation of dispersed hippocampal culture with high-density CMOS multielectrode array based on non-Faradaic electrodes

We introduce a method to electrically stimulate individual neurons at single-cell resolution in arbitrary spatiotemporal patterns with precise control over stimulation thresholds. By exploiting a custom microelectronic chip, up to 65,000 non-Faradaic electrodes can be uniquely addressed with electrode density exceeding 6500 electrodes mm(-2). We demonstrate extracellular stimulation of dispersed primary hippocampal neuronal cultures using the chip at single-cell resolution.

Morphogenesis, morphology and men: pattern formation from embryo to mind

In 1952, Alan Turing published his last work on the concept of embryonic morphogenesis, propounding a computational framework for pattern formation within the developing embryo. This concept of morphogenesis and the concept of embryo pattern formation based on chemical diffusion patterns were corroborated with the discovery of the Homeobox or Hox genes. In the following decades, Hox gene research has expanded and is now shown to underlie the variety of morphological novelties that we experience in nature, the patterning of structural aspects of different organs including the brain and also mutant animals that may in the future give rise to novel speciation. Turing had the foresight and vision and with his work created the field of computational biology and mathematical modeling in biological systems. In this paper, we will discuss the concept of Hox genes, their role in patterning the embryo, how it relates to Turing’s concept of morphogenesis and what further insights they may provide.

An electrically-stimulate optically-record microsystem based on active CMOS multi-electrode array for dissociated cell cultures

Calcium fluorescence-based optical recording combined with patch-clamp stimulation has become the standard technique for analyzing neural network behavior. At best, stimulation is limited to only a few channels in this case. Passive multielectrode arrays for two-dimensional electrophysiology only offer electrode densities of 60 electrodes per mm2. Here, we report an active multielectrode array, constructed with a standard complementary metal-oxide-semiconductor (CMOS) technology, to perform localized extracellular stimulation of dispersed cell cultures. A 256×256 array integrated with in-pixel stimulators on a 4-by-4 mm2 CMOS chip noninvasively stimulate hippocampal cells cultured on chip at cellular resolution. Combined with calcium imaging using high-affinity indicators, we demonstrate the ability to observe spatiotemporal dynamics of neural activity.

Games of Chance: Explorations into Our Animal Selves

Games of Chance: Explorations into our Animal Selves Siddharth Ramakrishnan and Victoria Vesna Neuroscience Program, Department of Biology, University of Puget Sound, Tacoma, WA -98416, sramakrishnan@pugetsound.edu 2 Design Media Arts, Art | Sci Center, University of California Los Angeles, Los Angeles, CA – 90095, vesna@arts.ucla.edu 3 Program in Empowerment Informatics, School of Integrative and Global Majors University of Tsukuba, Tennodai, Tsukuba 305-8573, Japan Abstract