Toward jet injection by continuous-wave laser cavitation

Abstract. This is a study motivated by the need to develop a needle-free device for eliminating major global healthcare problems caused by needles. The generation of liquid jets by means of a continuous-wave laser, focused into a light absorbing solution, was studied with the aim of developing a portable and affordable jet injector. We designed and fabricated glass microfluidic devices, which consist of a chamber where thermocavitation is created and a tapered channel. The growth of a vapor bubble displaces and expels the liquid through the channel as a fast traveling jet. Different parameters were varied with the purpose of increasing the jet velocity. The velocity increases with smaller channel diameters and taper ratios, whereas larger chambers significantly reduce the jet speed. It was found that the initial position of the liquid–air meniscus interface and its dynamics contribute to increased jet velocities. A maximum velocity of 94±3  m/s for a channel diameter of D=120  μm, taper ratio n=0.25, and chamber length E=200  μm was achieved. Finally, agarose gel-based skin phantoms were used to demonstrate the potential of our devices to penetrate the skin. The maximum penetration depth achieved was ∼1  mm, which is sufficient to penetrate the stratum corneum and for most medical applications. A meta-analysis shows that larger injection volumes will be required as a next step to medical relevance for laser-induced jet injection techniques in general.

[1]  Robert Krysiak,et al.  Growth hormone therapy in children and adults. , 2007, Pharmacological reports : PR.

[2]  Kazuyoshi Takayama,et al.  Shock wave driven liquid microjets for drug delivery , 2009 .

[3]  M. Kendall,et al.  Intradermal ballistic delivery of micro-particles into excised human skin for pharmaceutical applications. , 2004, Journal of biomechanics.

[4]  R. C. Garner,et al.  The utility of microdosing over the past 5 years. , 2008, Expert opinion on drug metabolism & toxicology.

[5]  Adam D. Maxwell,et al.  A tissue phantom for visualization and measurement of ultrasound-induced cavitation damage. , 2010, Ultrasound in medicine & biology.

[6]  Suraj Pant,et al.  The State of the World's Antibiotics 2015 , 2015 .

[7]  Joseph M. Mansour,et al.  Nondestructive Evaluation of Hydrogel Mechanical Properties Using Ultrasound , 2011, Annals of Biomedical Engineering.

[8]  Masaharu Kameda,et al.  Effects of a water hammer and cavitation on jet formation in a test tube , 2015, Journal of Fluid Mechanics.

[9]  Fedir V. Sirotkin,et al.  Laser-induced microjet: wavelength and pulse duration effects on bubble and jet generation for drug injection , 2013 .

[10]  Cees W J Oomens,et al.  Penetration and delivery characteristics of repetitive microjet injection into the skin. , 2016, Journal of controlled release : official journal of the Controlled Release Society.

[11]  Jack J. Yoh,et al.  A laser based reusable microjet injector for transdermal drug delivery , 2010 .

[12]  M. Kendall,et al.  Engineering of needle-free physical methods to target epidermal cells for DNA vaccination. , 2006, Vaccine.

[13]  Andrew Taberner,et al.  Needle-free jet injection using real-time controlled linear Lorentz-force actuators. , 2012, Medical engineering & physics.

[14]  Claus-Dieter Ohl,et al.  Fast transient microjets induced by hemispherical cavitation bubbles , 2015, Journal of Fluid Mechanics.

[15]  Sang-Heon Cho,et al.  ORIGINAL ARTICLE DOI: 10.3904/kjim.2010.25.2.207 The Current Practice of Skin Testing for Antibiotics in Korean Hospitals , 2022 .

[16]  J. Lévêque,et al.  Mechanical properties and Young's modulus of human skin in vivo , 2004, Archives of Dermatological Research.

[17]  Savanna R Reid,et al.  Injection drug use, unsafe medical injections, and HIV in Africa: a systematic review , 2009, Harm reduction journal.

[18]  S Annaheim,et al.  Materials used to simulate physical properties of human skin , 2016, Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging.

[19]  Bruce G. Weniger,et al.  Alternative vaccine delivery methods , 2012, Vaccines.

[20]  Samir Mitragotri,et al.  Jet injection into polyacrylamide gels: investigation of jet injection mechanics. , 2004, Journal of biomechanics.

[21]  John R Mascola,et al.  Comparative evaluation of three different intramuscular delivery methods for DNA immunization in a nonhuman primate animal model. , 2006, Vaccine.

[22]  Ian W Hunter,et al.  Needle-free delivery of macromolecules through the skin using controllable jet injectors , 2015, Expert opinion on drug delivery.

[23]  Seonggeun Lee,et al.  Towards clinical use of a laser-induced microjet system aimed at reliable and safe drug delivery , 2014, Journal of biomedical optics.

[24]  Neena Gupta,et al.  Awareness and Practices on Injection Safety among Nurses Working in Hospitals of Pokhara, Nepal , 2014 .

[25]  A. Prüss,et al.  Safe management of wastes from health care activities , 2001 .

[26]  Guillermo Aguilar,et al.  Optic cavitation with CW lasers: A review , 2014 .

[27]  Detlef Lohse,et al.  Breakup of diminutive Rayleigh jets , 2010, 1011.0320.

[28]  Kester Nahen,et al.  Dynamics of laser-induced cavitation bubbles near elastic boundaries: influence of the elastic modulus , 2001, Journal of Fluid Mechanics.

[29]  Patrick M. M. Bossuyt,et al.  Nonsurgical Repigmentation Therapies in Vitiligo , 2017 .

[30]  Kuo-Kang Liu,et al.  Characterizing the viscoelastic properties of thin hydrogel-based constructs for tissue engineering applications , 2005, Journal of The Royal Society Interface.

[31]  Chao Sun,et al.  Highly focused supersonic microjets: numerical simulations , 2012, Journal of Fluid Mechanics.

[32]  R. Heine,et al.  The Medi‐Jector II: Efficacy and Acceptability in Insulin‐dependent Diabetic Patients With and Without Needle Phobia , 1988, Diabetic medicine : a journal of the British Diabetic Association.

[33]  A. Aggarwal,et al.  Timing and dose of BCG vaccination in infants as assessed by postvaccination tuberculin sensitivity. , 1995, Indian pediatrics.

[34]  A. Sintov,et al.  Radiofrequency-driven skin microchanneling as a new way for electrically assisted transdermal delivery of hydrophilic drugs. , 2003, Journal of controlled release : official journal of the Controlled Release Society.

[35]  Detlef Lohse,et al.  Needle-free injection into skin and soft matter with highly focused microjets. , 2012, Lab on a chip.

[36]  P. Home,et al.  New Insulin Glargine 300 Units/mL Versus Glargine 100 Units/mL in People With Type 2 Diabetes Using Basal and Mealtime Insulin: Glucose Control and Hypoglycemia in a 6-Month Randomized Controlled Trial (EDITION 1) , 2014, Diabetes Care.

[37]  Tow Chong Chong,et al.  Laser-induced cavitation bubbles for cleaning of solid surfaces , 2004 .

[38]  Stanislav F. Rastopov,et al.  Sound generation by thermocavitation-induced cw laser in solutions , 1991, Other Conferences.

[39]  Samir Mitragotri,et al.  Needle-free delivery of macromolecules across the skin by nanoliter-volume pulsed microjets , 2007, Proceedings of the National Academy of Sciences.

[40]  A Robledo-Martinez,et al.  Time-resolved analysis of cavitation induced by CW lasers in absorbing liquids. , 2010, Optics express.

[41]  W. Lauterborn,et al.  Cavitation erosion by single laser-produced bubbles , 1998, Journal of Fluid Mechanics.

[42]  Yuichi Sugiyama,et al.  Impact of microdosing clinical study -- why necessary and how useful? , 2011, Advanced drug delivery reviews.

[43]  Kester Nahen,et al.  Dynamics of laser-induced cavitation bubbles near an elastic boundary , 2001, Journal of Fluid Mechanics.

[44]  K A Holbrook,et al.  Regional differences in the thickness (cell layers) of the human stratum corneum: an ultrastructural analysis. , 1974, The Journal of investigative dermatology.

[45]  Chao Sun,et al.  Highly Focused Supersonic Microjets , 2011, 1112.2517.

[46]  H. Mallmin,et al.  Cortisone Injection With Anesthetic Additives for Radial Epicondylalgia (Tennis Elbow) , 1995, Clinical orthopaedics and related research.

[47]  D. Tobin,et al.  Nano-scale observations of tattoo pigments in skin by atomic force microscopy. , 2015, Current problems in dermatology.

[48]  Gideon Kersten,et al.  Needle-free vaccine delivery , 2007, Expert opinion on drug delivery.

[49]  R. Cady,et al.  Needle‐Free Subcutaneous Sumatriptan (Sumavel™ DosePro™): Bioequivalence and Ease of Use , 2009, Headache.

[50]  Claus-Dieter Ohl,et al.  Oscillate boiling from microheaters , 2016, 1604.02666.

[51]  Samir Mitragotri,et al.  Needle-free jet injections: dependence of jet penetration and dispersion in the skin on jet power. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[52]  P M Bossuyt,et al.  Nonsurgical repigmentation therapies in vitiligo. Meta-analysis of the literature. , 1998, Archives of dermatology.

[53]  K. Zaman,et al.  Spreading Characteristics and Thrust of Jets from Asymmetric Nozzles , 1996 .

[54]  Samir Mitragotri,et al.  Micro-scale devices for transdermal drug delivery. , 2008, International journal of pharmaceutics.

[55]  Ruben Ramos-Garcia,et al.  Continuous-wave laser generated jets for needle free applications. , 2016, Biomicrofluidics.

[56]  E. Villermaux,et al.  Physics of liquid jets , 2008 .

[57]  H. Wulf,et al.  Epidermal thickness at different body sites: relationship to age, gender, pigmentation, blood content, skin type and smoking habits. , 2003, Acta dermato-venereologica.

[58]  T Gibson,et al.  Local injection treatment of tennis elbow--hydrocortisone, triamcinolone and lignocaine compared. , 1991, British journal of rheumatology.

[59]  N. J. Chinoy,et al.  Microdose vasal injection of sodium fluoride in the rat. , 1991, Reproductive toxicology.

[60]  Karen Hogan,et al.  A “Needling” Problem: Shoulder Injury Related to Vaccine Administration , 2012, The Journal of the American Board of Family Medicine.

[61]  Claus-Dieter Ohl,et al.  Cavitation bubble dynamics in microfluidic gaps of variable height. , 2009, Physical review. E, Statistical, nonlinear, and soft matter physics.

[62]  S. Vassileva,et al.  Medical applications of tattooing. , 2007, Clinics in dermatology.

[63]  Samir Mitragotri,et al.  Dynamic control of needle-free jet injection. , 2009, Journal of controlled release : official journal of the Controlled Release Society.

[64]  Hun-jae Jang,et al.  Er:YAG laser pulse for small-dose splashback-free microjet transdermal drug delivery. , 2012, Optics letters.