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Non-lethal Weapons Study

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Sensory Consequences of Electromagnetic Pulses Emitted by Laser InducedPlasmas

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Non~lethal Weapons Study

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Sensory Consequences of Electromagnetic Pulses Emitled by Laser InducedPlasmas

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Section C - DesCriptions and Specifications

STATEMENT OF WORKCl Statement ofWorlc

CLIN 0001 and Option CLIN 0002 shall be in accordance with the Statement of Work attached to this contract.

/\,

Section J - List of Documents. Exhibits and Other Attachments

Exhibit/Attachment Table of Contents

( M67854-04-C-5074

Page 24 of24

DOCUMENT TYPEAttachment 1

DESCRIPTIONStatement of Work

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M67854-04-C·5074Attachment 1

Statement of Work

I. Technical

A) Objectivestrasks/Concept. Recent advances in directed energy weapons technology suggests thatscalable, non-lethal to lethal force systems may be possible. Such a system would be useful in manyenvironments. Two systems currently under development, active denial and pulsed ener ADS andPEP offer mainly complementary ca acities that could address multi Ie tasks

ese tasks include theThe full capability of these directed energy

systems (DE) are still being explored. At their current stage ofdevelopment, each system has clear non­lethal (ADS) and lethal (PEP) capacities suitable to the above tasks. Our experiments will examine thefeasibility of PEP as a new generation non-lethal wea on. Pulsed ener can be confi ed to roduce

lasmas of exce tionall hi enerIn the

studies described below we will determine the feasibility of using the plasma derived EMP to induce painsuitable to disarm and deter individuals or form barriers to the movement oflarge hostile groups. Ifsuccessfully deployed, PEP could complement ADS in situations in which the latter is ineffective, lesseffective, or rone to countermeasures. Many of the countermeasures that might be envisioned againstADS offer opportunities for PEP targeting (via plasma induction orablation of the defense). Despite these potential advantages, certain special capabilities and features ofADS offer advantages over PEP in many scenarios. Therefore, the systems are complementary.

The efficiency and lethality of PEP weapons systems lll'0 straightforward. The non-ballistic, instantaneous properties ofDEmake precise tlll'geting a straightforwlll'd matter of line ofsi l. Terrific amounts of ener can be delivered over greatdistances with pinpoint accumc . However, Potentially.the lication of PEP

proposal.

uantify tho. characteristics oflaser induced plasmas created.~with micro-, nano- ico- and femtosecond lasers ofmulti Ie

These studies will examine the characteristics ofIn the studies described below, we will describe investigations that explore the

human effects ofLIP. Studies are proposed to detennine the capacityof_oevoke pain. These studies will beperformed, in vitro, where the factors such as distance and orientation can be tightly controlled, and whereth~ painsystem components can be isolated for detailed quantitative ",udy. A portion of the investigotions will apply_tosensory eell preparations. These.wi.be generated by conventional means. Subsequent studies will use laser-inducedplasmas to create . the characteristics of which will be well defined andoptimized to produce atraumatic sensory influences.

Objective I: To determine the feature. bat activate nociceptor. and tbe extent to whicb thisactivation Js effective without trau.ma. Pain is a primary component of all NLW. Pain can distract and deter individualsresulting in voluntary immobilization and/or flight. Nociceptors are the fundamental delection component ofthe pain system.Nociceptors transduce a variety of stimuli (gated ionic current) and then encode the pain signal (action potentials). While themechanisms are not fulJy understood. ADS operates mainly on the transduction component by heating biological tissue toactivate heat transducing proteins at asuh-tra~wave Techniques for Stimulation ofNociceptors.NTIC proposal, October, 2003). In contrast, _ could activate nociceptors at the level of

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M67654-04-C-5074Attachment 1

Statement of Work

encoding, thereby bypassing the transduction level. Induction at the encoding level is potentially more advantageous. as itavoids thedirect~d the risk that occurs from this time dependent event. Moreover, by engaging theencoding event, _ will not rely solely on specialized transduction proteins that are selectively expressed in asubpopulntion ofsensory afferents. Although they differ in i."fenn anddi,tri~Uu th.t medi.te eneoding arepresent in all excitable tissue. In objective 1, we will deternllnc the influence~n nociceptor activation,focusing specifically on cutaneous nociceptors that innervate superficial skin (epidenois) and underlying tissue (demtis). The• strength required to induce activation, the contribution of pulse duration and burst frequency will be defined in tightlycontrolled experiments, in vitro. These data should prove to be very useful in interpreting the potential bwnan effects of LIP,and its potential as a NLW.

Objective 2: To eJ:amJoe tbe influenceof_laserplasmas, OD nociceptor activation aod determine tbeextent to which tbls activation 10 effective without trauma. Completion ofobjective I will enable a set ofh theses that~fobjective 2. With an understanding of the 'safe'par~for_, directed choices can be made to study particular laser _ configurations onnocice~identical recordin methods ut lascr stimulation) we will examine the nociceptor activating properties oflaser_

configumtion and stimulation regimes.

B) Background

Laser Plasma Technology. There is increasing interest in the use oflasers for non-conventional defense applications. This isnot only a consequence ofthe recent heightened sensitivities in such areas as homeland security. defense force prolection, andlaw enforcement, but it also comes from new technical opportunities becoming available through the increasing pace ofdevelopments in laser technology. Developments in solid state laser technology in particular are leading these advances.Diode-pumping, for instance, for the first tiroe enables electrical pump energy to be selectively channeled to spccific lasertransitions within solid-state laser media, leading to vast improvements in laser efficiency, compactness and stability. Newevolutions in laser architecture, like fiber-lasers, slab-laser amplifiers, active phase control and ultra-short pulse technology arerapidly opening up new parameter space in sciences and technologies having possible relevance to new defense applications.One of these areas is th~ field of laser plusmas.

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M61854-04-G-5014Attachment 1

Statement of Work

In the new realm ofhigh intensity femtosecond laserof laser interaction science has been accessed leadin

Assuming that the cro,,-section ofthese highly transienttargeL Given that they~ times measured in picoseconds, the frequency ofsouree would be in the-",gion. However, to date, little research has verified the

There is extensive interest in developing weapons systems that utilize pulse energy projectiles (PEP). When appropriatelyconfigured, a PEP could serve both lethal and non-lethal lications. The guiding hypothesis of this proposal is that thecreation ofLIP can serve as a NLW by activation ofnocicepoors.

The Peripheral Pain System. The detection ofpain begins with a complex set ofperipheral afferents (nociceptors) that detectand encode a great variety ofstimuli. These peripherally encoded events are relayed by axons into the central nervous system(spinal cord, thalamus, cortex) where the information undergoes the complex assembly required to produce a localized,conscious perception ofpain (Cooper and Sessle, 1993). Nociceptive atferents detect tissue damaging or near tissue damagingconsequences ofmechanica! and thermal events, and the chemical events associated with actual tissue damage. To accomplishthese multilevel tasks, the pain system has evolved a family ofnociceptive neurons with dive"" mechanical, thermal andchemical response capacities. These capacities overlap in a manner that is not completely understood, but it is likely that theyvary for particular tissue sites (skin, joints, muscle, viscera, bone) that have highly specialized nociceptive requirements.Recent advances in nociceptor characterization have permitted classification, In Vi/TO. ofatlcast 8 distinct nociceptivephenotypes. Our laboratory has shown that sensory cells ofthe DRG are comprised ofdiscrete, internally homogenous, classesofcapsaicin (OC) sensitive (types I, 2, S, 7, 8 and 9) and insensitive (types 3, 4, 6) populations with distinct capacities torespond to SHT, PGEz, protons, ACh and ATP (Martenson et al., 1994; Cardenas et al., 1997; Cardenas et ai, 1999; Petruska etaI., 2000, 2002; Cooper and Cooper, 2001). We have used lipid soluble fluorescent tracers to define the specific distribution ofnociceptors into viscera, joints and skin. Prc:liminary studies have indicatedtha~pu1ationsofskinin~~ S. It is these nociceptors that are likely to receive the maximal burst _ from laser plasmas _

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M67854-04-C-5074Attachment 1

Statement of Wor!<

The capacity of a nociceptor to detect and transduce noxious stimuli (heat, mechanical, chemical) is due to the presence ofmembrane imbedded proteins which act as transducers. Specific proteins have evolved which alter conformation in thepresence ofheat, chemical ageots, This altered conformation gates a pore to allow ions to pass along theirelectrochemical gradients. Microwave radiation. via its capacity to beat tissue, is likely to interact with certain heat sensingproteins that are differentially expressed in nociceptor subpopulations (TRPVI, TRPV2; Caterina et al., 1997, 1999; Tominagaet aI., 1998). Such proteins are likely to be the ultimate targets of ADS millimeter wave radiation. In addition to detection andtransduction of noxious events, nociceptors, like alt sensory afferents must encode the event so that it can be relayed to thecentral nervous system where perceptions are fonned. Each nociceptor emits a code in the form ofa series of action potentialsthat are produced in a frequency that is in proportion to the ionic current of the transduced event. The action potential codearises from the influence of the ionic current on clusters of voltage-gated channels. This can be thought ofas an analog todigital conversion, where the ionic current is the analog signal that is converted to a digital code by the cluster of voltage gatedchannels. This cluster is composed mainly of volrage gated Na+, K+ and Ca- channels. Each channel is composed ofmultipleproteins that fann an ionic pore in the neuronal membrane and contain a distinct voltage-sensing region. Sensitivity to internalvoltage vanes considerctbly in sensory systems due to the differcntiw distributi<)fi and multiple isoforms of voltage gatedchannels. Voltage gated Na channels (No,) are responsible for the upstroke of the action potential while voltage gate K+channels (1(,) are responsible for the downstroke. Multiple forms of No, and K, have evolved to set characteristic frequencyresponse rates in different afferent populations. Nocice tora contain multi Ie forms of these channels a. 1.7, 1.8 and 1.9;~2002; Djoubri et al., 2003a,b)._ Those Na, subtypes that are mainly foun 1D noclceptors (Na,I.8 and Na,I.9) have relatively high thresholds andslow kinetics. Due to the ultra slow kinetics ofNa,1 .9, only Na.,1.8 participates directly in action potential generation (Elliottand Elliot, 1993; Akopian et al., 1996; Tate et aI., 1998; Cummins et al., 1999; Dib-Hajj et al., 2002).

C) Technical Approach and Methodology

Overview of Experiments. The goal of the studies, in year 1, will be: I) to determine the nano- and micro-pulsedregimes that initiate nociceptor activation; 2) to determine the range of frequency modulation ofthe nociceptive signal that canbe produced; 3) to determine the differential influence on distinct skin nociceptor phenotypes; and 4) to determine the pOint atwhich trauma might begin to limit the NLW value created. The body of knowled e acquired in year I will guide thedevelopment ofhypotheses regarding the desired features of a lasma . The e eriments of ear two will testthese h otheses using a variety oflasers

opefully we will be able to marry these two bodies of knowledge and perfect a laboratory scale NLWlaser plasmas.

These studies will be conducted in vitro, where nOCiCntiVe cells of several phenotypes can be exposed to well specified,intens~burststhat simulate exposure to laser Due to methods developed in our labomtory, we are able toidenti~e nociceptive phenotypes that are subpopulations of a large population of sensory cells that mediate touch,proprioception, warmth, cooling, itch and pain sensations (petruska et al., 2000, 2002). The identified nociceptivesubpopulations have been shown to be heat sensitive and thereby involved in the transduction ofbuming pain sensations

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M67854-04·C-5074Attachment 1

Slatement of Work

In our studies we will present high intensity nanosecond-micosecond pulses to cutaneous nociceptors@£...arbocyanine dye tracing). These nociceptors express distinct Na, that are likely to manifest differential sensitivity __ activation. We will detennine the threshold for activation for nano- and micro- pulsed _ the effuct of repeatedpulsing, pulse duration and intensity. If activation is discrete, we should be able to drive nociceptors in a pulse.by-pulsemanner. Alternately, single pulses in these time and intensity domains may not be able to produce any activation. In thisinstance, burst application that approaches known thresholds o_effectiveness (I msec) could be used. We will conductsuch single, multiple and burst train studies at various power and duration combinations in multiple nociceptive subtypes. Wewill parallel these studies with examinations membrane damage suggestive of electroporatioD, cell trauma and death.

Due to limits of the current technology for delivering high~ulses,we will not be able to test in the femto- andpieosecon~ns in year 1. On the one hand, that will limit our ability to form hypotheses that simplify studies ofyear 2involving _ single pulse femto- and picosecond lasers. On the other hand, the shoIter the duration ofthe burst, the lesslikely it will work in single pulse mode. In year 2, _~ese time domains can beexamined. We might find that they work in burst mode, where the duration _ can be functionally eXlendedinto the nanosecond time domain. To that ex.tent, the nanosecond could successfully emulate a burst offemto- andpicosecond laser . Femto second lasers have logistic advantages over other configurations.

In year 2, we will use our acquired knowledge of pulse duration, frequency and burst regimes to select laser _ withhigh promise for NLW effectiveness. Based upon studies using a high repetition-rotc (100 Hz) Q-switched Nd: VAG laser andtwo ad . . that use an 0 n-arcbitecl\m solid-slate oseillator-multi-amplifier system ofour own design,

we will bave determined the characteristics _ that best match thosepropeIties we predict (from year 1) will have atraumatic NLW effec1iveness. In year 2 we will confirm these hypotheses(adjust as necess and examine whether the influence on nod tors are robust with res ct to variations. These variations

lid includeWe will again examine neurons for evidence ofdamage due to . While the methods of

stimulation differ considerably, the methods of recording from cells will remain the same. Because of the use oflasers in yeartwo, the studies will shift to the University ofCentral Florida site (M. Richardson laboratory). Neural recording equipmentwill be shipped to the site, and some additional purchases will be made for auxiliary instruments that would be needed at thenon-UF location.

Nociceptor RecordIngs. Conventional whole cell patch recordings would be desirable and could bemade in many ofthe planned experiments. Thes.alwa. be suitable for classification of nociceptive cells at the beginningofeach experiment prior to the application of . These methods may be suitable for recording during single ordispersed pulses. However, as the duty cycle or burst frequency increases, the ability to make such recordings byconventional methods is less likc:ly. Therefore we will plWl to use 0 tical methods to assess action potential discharge.Accordingly, cells will be perfused witb~nsitive dye . Hi resolution~urement is possible under thesc conditions,--.All recordings are conducted at 35° C.

Procedures: Nociceptor Activation. Once the whole cell patch configuration is achieved, cells are classified by physiologicalcriteria associated with nociceptors (voltage clamp mode; see Petruska et a1. 2000, 2002). The main studies arc carried out incurrent clamp mode. The cell (20-45 urn diameter) is centered in the field (eyepiece reticule). The microscope is configuredfor -'pplication by the introduction of a pair ofstainless steel plate electrodes tbat have been pre-positioned to bracketthecel~n (3 mm, se aration. Durin rccordin SJ cells are exposed to nano- or microsecond pulses from oneof the _ pulsers . These devices can produce pulse durations from 10nanoseconds to 100 microseconds . High exposures are commenced at planned intensities, durations,repetition rates, and burst frequencies. Optical recordings are made continuously and captured by software for analysis,Studies will define the minimum field characteristics that produce activation, and then proceed with higher burst frequencies,longer duralions and more intense fields to determine the limits of activation and thiint at which trauma occurs. Unconventional records. we will monitor RMP at regular 'rest' intervals. •

Studies will proceed on a variety of skin nociceptive phenotypes (types 1,2,4 and 5). Differences insusceptibility are likely to be observed due to quantitative and differential expression ofTTX sensitive channels (Na,1.7 vsNa"I.8). We will~mM) or ITX (I uM) to determine whethertbe dye emissions are due to gating ofNa,. or adirect influence of dye emission. Some time limited artifact is expected.. Ifprolonged, false signals are

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M67854-04-C-5074Attachment 1

Statement of Work

indicated, we will shift to Ca++ sensitive dyes. We will also consider thennal contributions by examining the inter-platetemperature shifts associated. with stimulation protocols.

Measurement of nano and micro pulsed E fields. We willdevis~s'- fields generated.These will be developments from devices we have used in the past--.and also devices developedspecifically for these studies.

The objective of these measurements will be to:

•

•

ofthe

detectors will be used for measurements _from lasmas created by nanosecond

We will also useWe will also use more sophisticated signs that have

rotection or defense

here will be to adapt these concepts, and utilize the broad depth ofknowledge into use with microscopic laser·plasma-based sources.

References

Akopian AN, Sivilotti L, and Wood IN. A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensoryneurons. Nature 379(6562): 257-262,1996.

Cardenas CG, Del Mar LP, Cooper BY, and Scroggs RS. SlIT. receptors couple positively to tetrodotoxin-insensitivesodium channels in a sub 0 ulatioDs ore saicin-sensicive rat senso neurons. Journal 0 Neuroscience 17: 7181-7189, 1997.

Caterina MI, Rosen TA, Tominaga M, Brake AJ, and Julius D. A capsaicin-receptor homologue with a high thresholdfor noxious heat. Nature 398: 436-441, 1999.

Caterina MJ, Schumacher HR, Tominaga M, Rosen TA, Levine JD, and Julius D. The capsaicin receptor: a heat·activated ion channel in the pain pathway. Nature 389: 816-824,1997.

Cooper, A. and Cooper B.Y. The Distribution ofoAChr in Subclassified Sensory Cells ofthe Rat DRG.Neuroscience Abstracts, 2001, 27, 2001.

Cooper, B.Y., Rau, K. and Jobnson, RD.. Heat Reactivity and TRP expression in Capsaicin Sensitive and InsensitiveSubclassified Sensory Cells ofthe Rat DRG, Society for Neuroscience 2003.

Cooper BY and Sessle BJ. Physiology ofnociception in the trigeminal system. In: The Headaches (I ed.), edited byOlesen J, Tfelt-Hanscn P and Welch KMA. New York: Raven Press Ltd, 1993, p. 87-92.

Cummins TR, Dib-Hajj SD, Black lA, Akopian AN, Wood IN, and Waxman SG. A novel persistent tetrodotoxin­resistant sodium current in SNS·nuli and wild-type small primary sensory neurons. J Neurosci J9: RC43, 1999.

Dib-Hajj S. Black JA, Cummins TR, and Waxman SQ. NaNlNavl.9: a sodium channel with unique properties. TrendsNeurosci 25: 253-259, 2002.

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Djouhri L, Fang X, Olruse K, Wood IN, Berry eM, and Lawson SN. The TTX-resistant sodium cbannel Navl.g(SNSIPN3); expression and correlation with membrane properties in rat nociceptive primary afferent neurons. J Physio/550;739-752,2003a.

Djouhri L, Newton R, Levinson SR. Berry CM, Carruthers B. and Lawson SN. Sensory and electropbysiologicnlproperties of guinea-pig sensory neurones expressing Nav 1.7 (PN1) Na+ channel alpha subunit protein. J Physio/ 546: 565­576,2003b.

-Elliott AA and Elliott JR. Characterization ofTIX-sensitive and TTX-resislant sodium currents in small cells from

adult rat dorsal root ganglia. J Physio/463; 39-56, 1993.Fang X, Djoubri L, Black lA, Dib.Hajj SD, Waxman SO, and Lawson SN. The presence and role of the tetrodotoxin-

resistant sodium channel Na v 1.9 in nocice live rim afferent neurons. J Neurosci 22: 7425-7433, 2002.

Martenson ME, Ingram SL. and Baumann TK. Potentiation of rabbit trigeminal responses to capsaicin in a low pHenvironment. Brain Research 651: 143-147, 1994.

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