IEEE EMBS Seminar May 24 2013 University of Texas at Dallas

PLEXON®, the five-line symbol, CinePlex®, DigiAmp™, Offline Sorter™, OmniPlex®, PlexBright™, PlexStim™ and Radiant™ are registered and unregistered trademarks of Plexon Inc, Dallas, Texas, USA. ©2013 Plexon Inc. All rights reserved. Other product and company names mentioned are trademarks or registered trademarks of their respective owners.

1 CONFIDENTIAL Interfacing to the Nervous System

Past, Present, and Future

2 CONFIDENTIAL Plexon Stats • Founded by Harvey Wiggins, initially as Spectrum Scientific in 1983 • A pioneer and leading innovator of custom, high performance data acquisition and analysis solutions specifically designed for research. • 30 years in business • Customers in ~40 countries • Supports research performed around the globe in fields including – fundamental neuroscience Headquartered in Dallas, Texas with – and BMI second office in Brussels, Belgium

– neurodegenerative diseases Distributors in Hong Kong, Japan, – addictive behaviors Taiwan, Korea, and Australia

• Cited in thousands of scientific publications

CONFIDENTIAL 3 Founded in 1983, Plexon now services over 1200 customers with industry leading technology

Corporate Timeline

Multi-electrode NIH SBIR DARPA Project Phase I and Subcontract 1200 Systems in Started Delivery of 1st Delivery of Duke 800 labs and With Dr. Don consortium NIH SBIR Production 150 Systems in Neuro- OmniPlex Woodward UTSW prototype Phase II MAP Systems 100 Labs prosthetics Development

1988 1989 1991 1994 2000 2002 2012

Staff 2 4 5 6 14 18 32

CONFIDENTIAL 4 Where did Plexon come from?

• Early 1950’s The A.C. Gilbert Company: Chemistry and Erector sets • 1957 Sputnik • 1959 High school science in the late 1950’s • 1960-64 College at UNT, math & physics • 1965-68 SMU and UTSW, biomedical engineering and computer science • 1968-69 Nuclear Chicago Corporation • 1969-1982 Callier Center/UTD and auditory research • 1983-95 Spectrum Scientific (propietorship) • 1996-now Plexon Inc (incorporated 1996)

CONFIDENTIAL 5 Plexon Core Technologies • Online neural signal acquisition in real time using DSP to produce a data stream of point-process events from the cell firings (action potentials or spikes). The event stream represents the neural activity in the anatomical area being studied as a function of changes in the animal or cell’s environment.

• interface devices – electrodes and electronics

• Video recording, tracking, and animal behavior recognition

• Electrical and Optogenetic stimulation

CONFIDENTIAL 6 MAP System Architecture 1990

7 CONFIDENTIAL MAP System Design Goals 1990 • 128 channels real time spike sorting • 40 KHz/channel simultaneous sampling, 12 bit • 8 channels per DSP chip • 16 DSP chips total, operating in parallel • Spike band only, 300 Hz – 8 KHz • Interface to ISA bus on PC with 486 processor • Point process (time stamp) + waveform segments • Remote preamp box + animal headstages

CONFIDENTIAL 8 DSP Module MAP DSP board design 1990

CONFIDENTIAL 9 Plexon technology enables advanced neuroscience research in a wide-array of fields

Basic Brain Research Robo-Rat

Brain-Machine Interface

Smart Mouse

Neurosurgery

Neuronal Cultures

CONFIDENTIAL 10 Groundbreaking research using Plexon technology

From Miguel Nicolelis 2003 Duke University 11 CONFIDENTIAL From Miguel Nicolelis 2003 Duke University

CONFIDENTIAL 12 Electrodes and implants

From Miguel Nicolelis 2003 Duke University

CONFIDENTIAL 13 Interfacing to the Nervous System - the Past The development of extracellular neurophysiology recording and computers in the laboratory are closely intertwined. The initial application of the first laboratory instrument computer was for auditory electrophysiology research. Later, minicomputers as developed in the late 60’s were used in many neurophysiology research applications.

Brain electrodes tended to be either sharp needle like stiff wires or small bundles of microwires (50 micron diameter)

CONFIDENTIAL 14 Past

LINC - Laboratory Instrument Computer developed at Lincoln Labs and MIT around 1962

CONFIDENTIAL 15 Past DEC PDP-12 late 60’s

CONFIDENTIAL 16 Past

Interdata 16-bit minicomputer Callier Center 1968 - 1971

4 KB magnetic core memory Teletype console device & 10 cps paper tape Triggered timer – 100 usec X-Y DAC for point plotting storage scope - Later added 300 cps tape reader

CONFIDENTIAL 17 Past DEC PDP-11 16-bit minicomputers Callier Center 1972 - 1984

PDP-11/20 and 11/23 - experiment interfacing PDP-11/45 central time sharing computer

CONFIDENTIAL 18 Past

Mid 90’s through the 2000’s

CONFIDENTIAL 19 16 channel MAP differential input signal board with Past high-pass and low-pass filtering, controllable gain, 12 bit A/D conversion

20 CONFIDENTIAL Interfacing to the Nervous System - the Present

The two major trends in interfacing to the nervous system are; miniaturization and better biocompatibility. Over the last 20 years the steady pace of electronic device miniaturization, along with lower power and higher density, has led to significant advances in implant technology, data bandwidth, and various optical techniques. New materials have drastically broadened the range of electrode designs and features. Increased power density has allowed implanted wireless devices to become more viable.

CONFIDENTIAL 21 Present

3/3/2010 CONFIDENTIAL 22 Present OmniPlex® Neural Data Acquisition System

• 16, 32, 48, 64, 128, 192 & 256 channels • 32 digital input channels - dual 16 channel ports, individual TTL or strobed word • Electrically isolated digital amplifiers • A/D input conversion 16-bit, 40kHz per neural channel, simultaneous sampling • Software selectable digital filtering for isolation of field potential and spike frequency bands • Online sorting in waveform space (time/voltage, using boxes, templates, lines, or bands) or directly in feature space (PCA, peak/ valley, and others)

CONFIDENTIAL 23 Present

OmniPlex with 64 channel DigiAmp OmniPlex with 256 channel DigiAmp

CONFIDENTIAL 24 Present Comparison of 16 channel signal boards: 1995 MAP box and 2010 DigiAmp

CONFIDENTIAL 25 Present Comparison of 512 channel quad-MAP box, 2003 and OmniPlex with 256 channel DigiAmp, 2010

CONFIDENTIAL 26 CONFIDENTIAL 27 Interfacing to the Nervous System - the Future

• Electrodes, coatings, improved materials • Miniaturization, implants, connections, wireless • and other opto- techniques • Large scale data handling • Large scale data analysis • Connectome, Connectomics • Neuractome, Neuractomics

CONFIDENTIAL 28 Future Comparison of 16 channel signal boards: 1995 MAP box and 2010 DigiAmp, with 2013 32 channel digitizing headstage

CONFIDENTIAL 29 Future 512 channel neural data acquisition; Past and Future

CONFIDENTIAL 30 Future

Active high density probes Intelligent electrode arrays Chip implants with stimulation

Electrode surface Polymer and other Optogenetics and other treatment and coatings biocompatible materials optical techniques

CONFIDENTIAL 31 Future Optogenetic Stimulation

PlexBright™ LED Optogenetic System

Royal 450nm • Super intensity fiber-coupled light output for in vivo or in vitro stimulation • Sub-millisecond response times Blue 465nm • Stable light output • Two controller options: Green 525nm – Stand-alone, single channel driver – Software driven, 4 channel controller

Yellow 590nm • Seven wavelength-specific modules Max Continuous Power delivered at tip of attached

Supply Current* 200/230µm fiber patch cable** Royal (450nm) 300mA 25 mW 796 mW/mm2 Orange 615nm Blue (465nm) 300mA 20 mW 637 mW/mm2 Green (525nm) 300mA 7 mW 223 mW/mm2 Yellow (590nm) 1000mA 4 mW 127 mW/mm2 Red 625nm Orange (615nm) 1000mA 11 mW 350 mW/mm2 2 Red (625nm) 1000mA 13 mW 414 mW/mm Crimson (645nm) 1000mA 13 mW 414 mW/mm2

Crimson 645nm • Optical patch cables with bare fiber tip, or LC ferrule/Fiber stub implant termination

CONFIDENTIAL 32 Future Optogenetic Stimulation

PlexBright™ 4-Channel Driver • The PlexBright™ 4 Channel Controller is the newest of two Plexon products to drive and control optogenetic stimulation. • It is a sophisticated, software driven, current and voltage pattern generator capable of driving stimulation through both lasers and LEDs and can be integrated with the OmniPlex D Neural Data Acquisition System.

CONFIDENTIAL 33 Future

Neural interface development at UTD

Rob Rennaker Biomedical Devices Center

Walter Voit shape memory polymer brain electrodes

Bruce Gnade materials and manufacturing techniques for electrodes

Jason Slinger conductive DNA and bioelectronics interfacing materials

CONFIDENTIAL 34