1. 工研院(南分院) 雷射應用科技中心 (顧問)
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

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 眼科應用 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 ~ 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 光 電 + 生 醫 NVI Bio-Medical Photonics Bio-medical
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

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 ( nm)
Diode ( 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
wavelength (um)

16. Absorption in Water/Tissue
Absorption (A)
2.94
1.93
CO2-laser
1.45
(microns)

17. Penetration-depth (d=1/A) vs. wavelength
UV VISIBLE Near-IR Mid-IR
( ) ( ) ( ) ( ) um
0.05 mm
( )
( ) mm
( )
( )
Water 3 absorption peaks: 1.45, 1.93, 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)
F* F
Depth (H)
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) For soft-tissue
1. Hemoglobin (blood)
2. Melanei (skin-color)
3. Water (Tissue)
4. Others (protein etc)
(2) Hard tissue (bones, teeth)
shock-wave
plasma-assisted
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 ( 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 ( nm),
IR-dye, HPPH, … IR-laser ( nm)
b) UV-laser excitation .. visible-laser fluorecense
c). Nano-particle ..(ITRI-2008)
nm ps-laser ,
Applications:
Cancer, tumor , antibody detection,
Psoriasis, acne,
Age-related macular degeneration (AMD)
hair-growth, wound-healing etc..

25. Optical Biopsy (breast cancer detection)
500 nm
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 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 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 ( 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, 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 ( 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, )
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)
5(horse) 20
4 (Crane)
3 (Pigeon) 10
-10
2 (Stingray) 7
1 (Frog) 5
-20
Pupil height (cm)
Near vision distance V = -100/ D (cm)

35. Stingray non-spherical eye-structure (to see both far & near)
Retina surface X' y
LENS
See far x
Optical θ
axis V H
Sinθ =H/V θ
See near D= 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 ( 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
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. 全球独一产品 激光 老视-治疗仪 Laser for Presbyopia PR-270 for patients age: 45-68
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=( ) 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-eye Retina-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 (1992).
3. 久保于市,Medical Applications of Lasers Tokyo, Japan page (1985).

48. 眼科, 美容及皮膚科 Conclusion (1) 醫療雷射之發展趨勢: (2) 光,機.電,生醫‧整合技術 光電、奈米、資訊、電機、電子、
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 !!