665 Fridman Blood

8/8/2019 665 Fridman Blood

1/6


2/6

This plasma technology can find many applications in the medical field. Within thehospital setting, this technology may prove useful in the operating room for patientssuffering from bleeding not amenable to other methods of coagulation. Because of thepotential for simultaneous sterilization, our device could also help prevent intra-

operative infections. Sterilization effects of non-thermal plasma are well-known [10-13] and were confirmed, for example, in our research with NASA Jet Propulsion Lab[14]. In the future, we intend to develop a significantly smaller version of our powersupply to create a portable, possibly battery-operated blood coagulator and woundsterilizer (Fig. 4). In addition, due to its ability to promote coagulation, the non-thermal plasma discharge device can be used for hemophiliac patients who haveclotting difficulties or those who are on anti-coagulants.

2. Experimental Setup

Schematics of our experimental setup of the varying and fixed (Fig. 4) frequency,voltage, and power Floating Electrode DBD setups are presented. Power of bothsystems is approximately 1 W/cm 2 and the treatment surface varies from less than

1cm 2 to 10cm 2 depending on the attached electrode (Fig. 6). Utilizing the variable frequency, voltage, and powersetup we are able to tune the setup for treatment dose appropriate for a specific application. I.e. for tissuesterilization we might want lower power with longer treatment time; while for blood coagulation we might wanthigh power with low treatment time to stop gushers large flow of blood; or lower power to coagulate bloodin small cuts.

Fig. 4. Floating Electrode DBD schematic.

We started a fundamental study of mechanism of blood coagulation with the help of electrical discharge plasma.Fig. 5 presents our setup for treatment of small blood volumes 500l. While not wasting too much blood pertest, this volume is a minimum required for standardized hematological tests we perform at the Drexel UniversityHahnemann Hospital hematology lab: PT (Prothrombin time), aPTT (activated partial thromboplastin time), andSTA-Thrombin (Diagnostica Stago proprietary Thrombin formation time test). In this setup we are able toprecisely control the distance of Floating Electrode DBD to the treated blood sample for the purpose of

Fig. 3. Quartz-coatedTreatment Electrode


3/6

determining correct dose required for clot formation and to get reproducible results necessary for thefundamental study.

Fig. 5. Blood treatment experimental setup schematic.

Schematic representations of the three treatment electrode types used for this research are shown in Fig. 6.

Round electrode is used for treatment of small areas and when distance between electrode and the treatedsurface is closely monitored (0.1mm). Wand electrode is used in hand-held operation where distance andtreated area are not precisely monitored. Roller is used for treatment of large flat areas.

Fig. 6. Treatment electrodes. Top: 3D models; bottom: schematic representations;left to right: round, wand, roller.

During treatment, tissue samples are placed directly on a grounded stainless steel plate. Blood samples aredispensed into 0.1 or 0.5 ml grounded stainless steel, aluminum, brass, or titanium containers (Fig. 5). For bloodtreatment we found titanium to be the best material where control blood sample coagulates the slowest.

3. Safety considerations


4/6

Safety of Floating Electrode DBD plasma electrode for humans needs to be considered for application in woundhealing. Here we consider a simplified electric scheme to estimate conditions required for electrical safety. Oncehuman approaches Floating Electrode, plasma ignites and at that point we can consider DBD plasma as capacitorand resistor in series and human as a resistor andcapacitor in series (Fig. 7).

Total plasma resistance can then be estimated as a sum of capacitive and active resistances:

( )2

21

p p p

p p p

i R R

C

R RC

= +

= +

Where p R

is total plasma resistance, pC is plasma

capacitance, p R is plasma active resistance, and is the

signal frequency. Similarly, total resistance of a human can be estimated as:

( )2

21h h

h

R RC

= +

Where h R

is total resistance of a human, hC is human capacitance, and h R is active resistance of a human. Forthe Floating Electrode DBD plasma device to be safe, total plasma resistance needs to be greater than totalresistance of a human:

( ) ( )2 2

2 21 1 p h

p h

R R

C C

+ >> +

Active resistance of a human is ~1 MOhm [15-17]and human capacitance is ~50 pF (though it rangesfrom 20 pF to 90 pF, depending on the surfacehuman is standing on, thickness of his/her soles,and distance to nearest grounded object) [15,17].For our frequency range, Floating Electrode DBDplasma active resistance can be estimated to 5 to 10MOhm and its capacitance to ~50pF [18,19]. Thusat the operating frequency of 12 kHz we see thattotal resistance of a human (1.9 MOhm) is far

smaller than total plasma resistance (5.3 MOhm), assuming hC =50 pF, h R =1 MOhm, pC =50 pF, p R =5MOhm. Even in the case where human total resistance will increase for some reason, total current passingthrough the human will be very low because of a massive total resistance of the system. From this estimation wecan conclude that even in the worst case where resistance of a human is approaching that of plasma, the overallsystem will still be completely safe from the electrical standpoint (Fig. 8).

4. Results

In our tests we have successfully accomplished the following:

Fig. 7. Plasma/human interface principal schematic.

Fig. 8. Floating Electrode DBD: safe to touch.


5/6

Designed and built a Dielectric Barrier Discharge (DBD) system capable of delivering 1 W/cm 2 of plasmapower at operating frequencies of 10-30 KHz. While the system employs a power supply delivering voltage of up to 10 KV, it is perfectly safe as the high frequency plasma current is limited to below a milli-ampere.

Developed treatment electrodes (Fig. 3-6) for treatment of blood and tissue samples. Performed blood coagulation tests on blood from cadaver organs (Fig. 9). The results consistently show faster

coagulation when exposed to DBD plasma: for example, blood treated for 15 seconds completely coagulates in2 minutes while untreated sample coagulates in 13 minutes.

Performed blood coagulation tests on cadaver organs with subsequent gross and microscopic evaluation of tissue to test for damage. Our analysis demonstrates blood clotting within 15 seconds without gross ormicroscopic evidence of tissue damage (Fig. 10,11).

Performed skin sterilization tests on cadaver skin with subsequent microbiologic culture. The resultsdemonstrate complete sterilization of skin flora after 6 seconds of treatment by the plasma.

Examined skin histology to find existence and/or extent of microscopic damage. No tissue damage was foundafter as much as 5 minutes of plasma treatment (Fig. 11).

Fig. 9. Plasma-assisted blood coagulation with 15-secondtreatment (left) and 1-minute treatment (right);control drop on the bottom, treated drop on top.

Fig. 10. 1-minute plasma treatment shows no visible tissuedamage. Left: before treatment; right: after treatment.

Fig. 11. Skin histology (left to right): control, 1 minute, and 5 minute treatment times show no detectable tissue damage.

5. Conclusion

This device can find many applications in the medical field, ranging from replacing high-power, high-temperature thermal plasma coagulators in the operating rooms to personal portable wound sterilizing andhealing instruments. The scope of the presented research included only initial studies of plasma influence onblood coagulation and simultaneous tissue sterilization. However, these studies are essential in providing us withknowledge and expertise on the underlying processes.

At the present, we are actively working on developing a kinetic model of DBD plasma influence on Bloodplasma coagulation cascade as well as DBD plasma role in the tissue sterilization process. We have interestingmodeling results (that agree with experimental evidence) involving DBD plasma influence on Calcium ion


6/6

concentration and in turn on blood coagulation cascade. These results will be presented at the ISPC-17conference.

Bibliography

[1] Hydrogen peroxide as a topical hemostatic agent, Clin Ortop. 1984 Jun; (186):244-8. Hankin FM,Campbell SE, Goldstein SA, Matthews LS.

[2] Clinical usefulness of 3% hydrogen peroxide in acute upper GI bleeding: a pilot study. GastrointestEndos. 1999 Apr; 49(4 Pt l):518-21. Kalloo AN, Canto MI, Wadwa KS, Smith CL, Gislason GT, Okolo PI3rd, Pasricha PJ.

[3] Hydrogen peroxide is involved in collagen- induced platelet activation. Blood.I998 Jan 15;91(2):484-90. Pignatelli P, Pulcinelli FM, Lenti L, Gazzangia PP, Violi F.

[4] Role of hydroxyl radicals in the activation of human platelets. Eur J Biochem. 1994 Apr l5; 221(2):695-704. Iuliano L, Pederson JZ, Pratico D, Rotilio G, Violi F.

[5] H 2O2 activity on platelet adhesion to fibrinogen and protein tyrosinephosphorylation. Biochim BiophysActa. 2000 Feb 2; 1495(2): 1 83-93.

[6] Free radicals contribute to platelet aggregation and cyclic flow variations in stenosed and endothelium-injured canine arteries. J Am Coil Cardiol. l994 Dec; 24(7):1749-56.

[7] A plasma scalpel: comparison of tissue damage and wound healing with electrosurgical and steelscalpels. Archives of Surgery Vol 11 l No 4, Apr 1976. W.J. Link, F.P. Incropera, J.L. Glover.

[8] The plasma scalpel: a new thermal knife. Lasers Surg Med. 1982; 2(1):I01-6. Glover JL, Bendick PJ,Link WJ, Plunkett RJ.

[9] Evaluation of the plasma scalpel for intracranial surgery: a pilot study. Surg Neurol. I 979 Sep;12(3):247-50. Payne NS, Tindall GT, Fleischer AS, Mirra SS.

[10] Biological decontamination by non-thermal plasmas. IEEE Trans. Plasma. Sci., Vol. 28, No. 1, pp. 184-188, 2000. M. Laroussi, I. Alexeff, W. Kang.

[11] A Remote Exposure Reactor (RER) for plasma processing and sterilization by plasma active species atone atmosphere. IEEE Trans. Plasma Sci., Vol. 28, No. 1, Feb 2000. J.R. Roth, D.M. Sherman, R.B.Gadri, F. Karakaya, Z. Chen, T.C. Montie, K. Kelly-Wintenberg, P.P.-Y. Tsai.

[12] Use of one atmosphere uniform glow discharge plasma to kill a broad spectrum on microorganisms. J.Vac. Sci. Technol. A., Vol. 17, No. 4, Jul/Aug 1999. K. Kelly-Wintenberg, A. Hodge, T.C. Montie, L.

Deleanu, D. Sherman, J.R. Roth.[13] Demonstration of a Hermetic Airborne Ozone Disinfection System: Studies on E. coli. AIHA J 64 no2

Mr/Ap 2003. W.J. Kowalski, W.P. Bahnfleth, B.A. Striebig, T.S. Whittam.[14] Final Technical Report - NASA Contract NAS3-01068 Use of Non Thermal Plasma for Sterilization of

Material Handling Devices[15] MARBLE, A. E., MACDONALD, A. C., MCVICAR, D., and ROBERTS, A., 1977, Phys. Med. Biol., 22,

365.[16] "Bioelectrical impedance measurements in patients with gastrointestinal disease: validation of the

spectrum approach and a comparison of different methods for screening for nutritional depletion",Petronella LM Cox-Reijven, Bernard van Kreel and Peter B Soeters, American Journal of ClinicalNutrition, Vol. 78, No. 6, 1111-1119, December 2003

[17] "Fusion Pore Conductance: Experimental Approaches and Theoretical Algorithms", Vladimir Ratinov, Ilya

Plonsky, and Joshua Zimmerberg, Biophys J, May 1998, p. 2374-2387, Vol. 74, No. 5[18] Electrical Characterization of a Corona Discharge for Surface Treatment, LA Rosenthal, DA Davis,

IEEE Trans. on Ind. Apps., Vol. IA-11, No. 3, May/June 1975.[19] Microdischarge behaviour in the silent discharge of nitrogen-oxygen and water-air mixtures, Z

Falkenstein, JJ Coogan, J. Phys. D: Appl. Phys., 30 (1997) 817-825.

Documents

665 Fridman Blood