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Recent Progress in Medical Laser Technologies ____________________________

Recent Progress in Medical Laser Technologies ____________________________. 醫 療 雷 射 技 術 之 最 新 進 展. J.T. Lin, Ph.D Chairman New Vision, Inc. 交通大學 ( 光電工程研究所 ) ( 客座教授 ) 工研院 ( 南分院 ) 雷射應用科技中心 ( 顧問 ) 鴻海 ( 精密工業 ) 股份有限公司 ( 顧問 ). 3-2008. Definitions. LASER L ight

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Recent Progress in Medical Laser Technologies ____________________________

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  1. Recent Progress inMedical Laser Technologies____________________________ 醫 療 雷 射 技 術 之 最 新 進 展 J.T. Lin, Ph.D Chairman New Vision, Inc. 交通大學(光電工程研究所) (客座教授) 工研院(南分院) 雷射應用科技中心 (顧問) 鴻海 (精密工業)股份有限公司 (顧問) 3-2008

  2. Definitions LASER Light Amplification by Stimulated Emission of Radiation (激光) -------------------------------------------------------------------------------- 雷射 (音譯) vs 激光(意譯) ---------------------------------------------------------------------------------------- 光子(Photon) vs. 光波(Wave) ----------------------------------------------- Diode vs. LED (laser) …………. (light)

  3. Historical • 1900 (Max Planck) …quantum mechanics 1917 (Einstein) …… A & B Coefficients 1954 (Townes)…... MASER (microwave) 1960 (Maiman)…… Ruby laser 1961 (Javan, Johnson) ……. HeNe, Nd:YAG 1962 (Bennett)…….. Argon laser 1964 (Patel) ………. CO2 laser The laser-patent war /Gordon Gould (1997). • 眼科應用 1983….. (UV-193 on organic tissue IBM Patent, ) 1990 …. PRK (vision correction, VisX patent) 1992 …. LASIK (Scanning) ( Lin’s patent) 1998 …. Presbyopia-I(Lin’s patent) 2008 …. Presbyopia-II , 3um didoe-laser (Lin)

  4. Overall Laser Applications 食,衣,住,行,育樂 國防,醫療、 資訊與通訊、 科技研發、 交通,工程施工,品管、 藝術活動、文物維護、 環境監測、

  5. SPECIAL Features of LASER: (1) 低發散性 (low divergence) 用於工程、環境、軍事、生物體等的遙測, 光纖通訊、光纖導航儀、光束武器、精密加工 等。 (2) 高強度 (high intensity): 光熱、光動力、光化學等作用 focused spot size (micron ~ 0.001 mm) (3) Pure-spectrum (narrow band-width): spectroscope, chemistry.. (4) Tunable spectrum (via non-linear processes) 非線性光學, 調變波長, 脈寬(pulse width) (5) 高相干性 (high Coherence) 用於藉干涉效應反映物質狀態及分佈、產生全像記錄 應用於檢驗、資料的高密度存取、藝術、防仿冒標籤等

  6. Non-medical applications • Military國防 - laser range-finder (1064, 1554 nm) - laser beam-weapon (STAR War) • Car industry: - speeding, counter-speeding - collision-free - auto-parking - overhead screen, GPS - auto-driven

  7. Bio-PHOTONICS Bio-medical Bio-Medical Photonics 光 電 + 生 醫 Photon + Electronics Biology + Medicine • Energy beams: Laser, LED, RF, non-coherent- light, Ultrasound • Optical materials • Fibers & beam delivery • Optical diagnosis, spectroscope • Electronic • System integration • Software & hardware • Bio-imaging, Bio-sensor • Photo-therapy (PDT) • Photo-biology • Surgical, coagulation • Drug delivery, tracking, characterization • Nano-medicine, bio-materials, bio-chem • Tissue Engineering/welding • Bionic human (artificial organs) NVI

  8. to be an Innovator (創 新 者) Innovation VS. Improving Know known Un-know known Un-know un-known Know un-known Rumsfield (2006) NVI

  9. 先 知 先 覺 ( Pioneer ) VS. 後 知 後 覺 ( Follower ) 創 新 者 (innovator) 知 人 所 不 知 也 ! Know un-known “物理”= 萬物之理也

  10. 工研院(南分院) 雷射應用科技中心 ITRI Projects前瞻性(原創性)新產品 (1) 高階(二類及三類產品) - 新雷射光源及光纖瓶頸技術之突破 - 臨床批准高門檻 (2) 新技術,新材料,新手術(關鍵性之專利) (3) 國內外皆尚未商品化 (4) 可於 2 ~ 3 年內產生跳躍式產業創新及 自有品牌新產品 . (5) 牙科,眼科,耳科,美容皮膚科及顯微手術之應用.

  11. Examples of innovation-IMPACT • Only < 1% patents has major financial impacts !!! (the METHODS patents) • IBM (1983 US patent): UV laser (193 nm, ArF) for all organic tissue ablation licensed to LaserSight for >$30M • Steve Troke (Columbia Univ.) 1986 US Pat…ArF for PRK/LASIK value : >$2.0 B • JT Lin (1991, 2000, 2004, 2006 US pat) scanning-laser for Lasik value > $500M • Shue Lai (1993) eye-tracking device, value >$200M JT Lin (1998).. laser for presbyopia value > $200M (???)

  12. Medical products development Idea, concept, theory Search, re-search Defining parameters Lab test, R&D Proto-type (1-2 years) Phase-I (Safety) Phase-II (Efficacy) Phase-III (Commercial) Clinical (Animal, human) (in Vitro, in Vivo) (1-8 years) FDA approval (510-K or PMA) System Integration & Commercialization (patents, improving) NVI Lin-7-2007

  13. Bio-Physics Laser-tissue interaction • Mechanisms: (Absorption, reflection, scattering) 1) Thermal 2) non-thermal 3) combined effects (Coagulation-ablation, cutting-incision) • Key parameters: Wavelength, Pulse width (Tp), Energy (E), Intensity (I), Power (P), fluency (F) Absorption coefficient (A), Reflection/scattering loss concept: F=E/ laser spot-size I= E/ pulse-width

  14. Thermal vs. Non-thermal • (1) Thermal: ( most cosmetic lasers): low-power, low intensity, long-pulse weak-absorption (A) , CW visible lasers, LED (400-700 nm) Diode (1.3-2.2 um) Ho:YAG (2.1 um), CO/2(10.6 um) • (2) Non-thermal (Lasik, kidney-stone, dental/hard-tissue) Short-pulse, high peak-power, Strong absorption (A>100 cm-1) (in water, tissue, melanin, protein , etc) short-pulsed (ps - fs) laser (independent to wavelength) Er:YAG (2.94 um), Excimer-laser (193, 248 , 308 nm)

  15. Absorption (blood, skin) melanin A HbO2 420 580 0.2 0.5 1.0 1.2 wavelength (um)

  16. Absorption in Water/Tissue Absorption (A) 2.94 1.93 CO2-laser 1.45 0 1.0 2.0 3.0 10 (microns)

  17. Penetration-depth(d=1/A) vs. wavelength UV VISIBLE Near-IR Mid-IR (0.2-0.4) (04.-0.7) (0.8- 2.1) (2.7-3.2) um 0.05 mm (0.2-0.5) (0.05-0.5) mm (0.5-2.0) (2.0-6.0) Water 3 absorption peaks: 1.45, 1.93, 2.94 um

  18. Laser Ablation Theory (1) Beers law: I(z) = I(0) Exp [-Az] (2) Ablation depth (H) is given by H = (1/A) ln (F/F*) where F*= threshold laser fluence for ablation to occur. optimal A* given by dH/dA = 0 A*=2.718 (F*/F) (3) Lin’s law (2005, for focused laser) I = B I(0) Exp(-Az) B=focusing factor for optimal depth. Depth (H) 0 F* F Depth (H) 0 A* A

  19. Laser heating theory Laser produced tissue temperature via heat conduction equation dT/dz = k (d2 T/dz2) where k=temperature conductivity Laplace transform or the Green function method to obtain T(z,t) = Integrate { S G dz dt } S is the heat source and G is the Green function given by G = C exp [ -(z-z0)^2 / 4k(t – t0) ] Thermal penetration depth d* = square root of (4kt) = 0.75 square root [laser pulse width] for d (in um)m and t (in usec). Example: for 1 usec laser, the heat conduction distance is about 0.75 um. The one-micron rule: ( t*=1.0 usec) short pulsed laser for non-thermal process. example: fiber laser (f.s.) Temp. time

  20. System design consideration 1. Hemoglobin (blood) 2. Melanei (skin-color) 3. Water (Tissue) 4. Others (protein etc) (2) Hard tissue (bones, teeth) shock-wave plasma-assisted (1) For soft-tissue Wrinkle-removal Hair-removal (invasive) PDT Non-invasive

  21. Major medical procedures 1.眼科 2. 美容及皮膚科 3. 泌尿科 4. 口腔科, 五官科 5. 婦科

  22. 泌尿科 (Prostate) • Technology: endoscope + laser + fiber • Laserscope, Inc. (acq. by AMS for $1.9 B) high-power (50-80 W) cw, green (532 nm) laser fiber-coupled ** side firing • Other lasers: Er:YAG (2.9 um) Ho:YAG(2.1 um), Th:YAG(2.07 um) diode-laser (1.4 – 2.9 um) 45-angle

  23. Dental lasers (1) Hard tissue (dentin, carries) a) Biolase “water-laser” (Er:YSGG at 2.78 um) b) Lin/ITRI, mid-IR diode laser (2.7-3.0 um) (2) Diode laser (soft tissue) at 808, 940, 980 nm (3) Teeth whitening Nd:YAG (1064) + dye (4) Velcope Blue-light (or LED) to detect cancer tissue

  24. Photodynamic therapy (PDT) • Laser-activated process a). Photo-sensitizers Red-dye, ALA… red-laser (630-660 nm), IR-dye, HPPH, … IR-laser (750 - 1200 nm) b) UV-laser excitation .. visible-laser fluorecense c). Nano-particle ..(ITRI-2008) 780-850 nm ps-laser , Applications: Cancer, tumor , antibody detection, Psoriasis, acne, Age-related macular degeneration (AMD) hair-growth, wound-healing etc..

  25. Optical Biopsy (breast cancerdetection) • Prof. Alfano at CCNY SPIE (2006, #6091) breast cancer detection: UV (282, 300 nm) as excitation, compare fluorescence spectra of normal and cancerous tissue Ratio: I/345 : I /500 = 3 to 5 times 500 nm UV 345 nm cancer

  26. Ultra-short-pulsed (USP) Lasers • USP laser (tp< 20 p.s.)…non-thermal • Applications: (1) high speed spectroscopy (2) 3-photon cancer diagnosis (1.2 um, third-harmonic) (3) corneal-flap for Lasik (Nd:YAG, 1064 nm) (4) materials process fiber-laser at 1030-1550 nm - Raydiance, Inc.(USA) - ITRI(工研院,南分院) for medical, industrial uses.

  27. Cosmetic Applications • 1). Hair removal Diode lasers (808, 940, 1064 nm) Alexandrite laser (at 760 nm, pulsed) (damage of follicle, hair-root ..) Hair-growth: red LED (630-680 nm) • 2). Skin Rejuvenation Invasive (Er:YAG, CO2), Non-invasive (1.32, 1.55 um) LED (880,630,580,420 nm) 3). lesions Acne (blue-LED/420 nm, IR fiber-laser/1550 nm) tatoo (ruby, N:YAG), spots (co2, Er:YAG, alex, dye laser) • 4). Psoriasis (excimer-308, red-LED/630) * non-laser methods: Radio-Frequency (MHz), microwave , UVA (--B) light pulsed-light (broad band, 400-1200 nm)

  28. Laser hair removal

  29. Wrinkle removal • (2) pigmented lesion • (3) vascular lesions • (4) acne • (5) leg veins (6) tatoo

  30. Home use hand-held LED 4- color LEDs : IR (940 nm) Yellow (580 nm) Red (660 nm) Blue (470 nm)

  31. Hair growth Laser-comb Red-LED (630-695 nm)

  32. 發展趨勢:Combining-energy (聯合療法) • Laser + LED + RF + Intense-Pulsed-light (IPL) 美白雷射、 去黑雷射、 退紅雷射、 脈衝光 (1) 鉺雷射(Er: YAG), (2) IR-diode laser (1.34,1.54,1.9, 2.8 um) (3) fiber-laser (FRACTOR)

  33. “Smart eye” designs(learned from nature’s evolution theory ) • On the origin of species by means of Natural Selection (Charles Darwin,1859) “Functional adaptation” is one of the important built -in survival mechanisms of all species. • Analysis of smart eyes with high power lens-accommodation (Lin, JCRS, 2007, 35, 758-759) Examples: Diving birds, sharks, octopus, Stingrays

  34. Low-field myopia theroy 腿短动物必定近视? V (cm) LFM (diopter) • Frog (1994) • 2. Stingray (1942) • 3. Pigeon (1942) • 4. Crane • 5. Horse (1975) 0 5(horse) 20 4 (Crane) 3 (Pigeon) 10 -10 2 (Stingray) 7 1 (Frog) -20 5 0 10 100 Pupil height (cm) Near vision distance V = -100/ D (cm)

  35. Stingray non-spherical eye-structure(to see both far & near) Y Retina surface X' y LENS See far x Optical θ axis V H Sinθ =H/V θ See near D= - 1000 H/ Sinθ (long axis) Object * Lin (2005, unpublished)

  36. Scan-195 LASIK System (developed by JT Lin, 1995)

  37. LASIK vs. PRK LASIK (stroma) PRK (surface) 2 steps 1-step + microkeratom

  38. Flying-spot scanning system* SCANNER 193 nm EXCIMER (ArF) Eye-tracking • Advantages of Scanning LASIK: • Smooth surface • Smaller energy/pulse ( 1 vs. 36 mJ) • Customized ablation for • super-vision (< 20/10) CORNEA * Lin (US Patent, 1992)

  39. Non-linear process • Harmonic generation 1064 >> 532 >>355 >>213 nm (KTP, LBO, BBO) 5-th harmonic (213 nm) for LASIK (Lin, 1992 US patent) • Optical Parametric Oscillation (OPO) for tunable lasers (0.6 -3.2 um) 1064 >> (1.5 to 3.2 um) ... KTP (Lin & Montgomery, 1989) 355 >> (0.6 to 1.3 um) .... BBO • Raman shift (SRS, SBS) (in methane, H2, D2 gas) 1064 (in CH4)>> 1.54 um (eye-safe range finder/Litton) 532 (in H2) >> 460(Stokes), 682 (anti-stokes)

  40. Diode-pumped solid-state LASIK 1064 532 532 266 213 Nd:YAG 1064 1064 KTP(II) BBO(I) BBO(II) Diode-pumped 100Hz, 40mJ 10 ns LBO(I) KDT(I) UV-213 100Hz 5 mJ Overall eff. 12% *UV-213 for LASIK (Lin, US patent, 1992)

  41. PR-270 激光 老视-治疗仪 Laser for Presbyopia 全球独一产品 UV-laser for patients age: 45-68 True accommodation 安全,不伤角膜(优于LASIK) 可一次做双眼(优于CK限单眼) 林氏动力二元论(JT Lin, JRS, 2005) J.T. Lin 2001年欧洲白内障与屈光手术会议(ESCRS) 提出LPT巩膜切除术后总调节度(accommodation amplitude） A=LR+AS, LR= 晶狀体变形(lens relaxation) AS= 晶狀体前移(anterior shift), AS=(1.0-1.5) D/mm New Vision, Inc.(2008)

  42. SCIENCE (September 29, 2006)

  43. The Bionic-human(2/2002, Science)

  44. Bionic Technologies • 1. Robotic hand • 2. Tissue repairing • 3. Artificial organs (heart, liver, blood) • 4. Bionic-eye Combined efforts of: bio-engineers, cell-biologists, clinicians

  45. Bionic-eyeRetina-simulation Micro-chip (3x3x1 mm)

  46. New Directions (The next 3-5 years trends) • - Innovative concepts for new methods & treatments - - - LED for low-cost light source (replacing lasers). - Diode lasers in Mid-IR (2- 3 microns), replacing Ho, Er:YAG - Ultra-short pulsed (fiber) lasers - Combined energy-beam: LASER, IPL, LED, RF • - New optical fibers (materials & structures) - Real-time image monitoring (endoscope) - More efficient, selective image detection devices in optical biopsy - Less-toxic agents, such as nanoparticles and new IR dyes, in PDT procedures.

  47. More New Directions • - Solid-state UV laser , replacing the toxic excimer laser • for LASIK. • - Femto-second lasers for • PDT, cancer diagnosis, • and blade-less LASIK - Multiple wavelength, multi-applications systems - Minimally invasive techniques for class II or II procedures. REFERENCES 1. J.T. Lin, Laser Applications in Ophthalmology, Jaypee Brothers (2008), 2 J.T. Lin, US Patent No. 5144630(1992). 3. 久保于市,Medical Applications of Lasers Tokyo, Japan page 186 (1985).

  48. Conclusion (1) 醫療雷射之發展趨勢: 眼科, 美容及皮膚科 泌尿科, 口腔科 五官科, 妇科 (type II, III)…market-driven (2) 光,機.電,生醫‧整合技術 光電、奈米、資訊、電機、電子、 影像、光纖 等 (3) 產、學、臨床,合作 Thank you for your attention !!

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