Development of Skin Stiffness-responsive Needle- free Injector = 피부 강성 반응형 무침주사기 개발

국문 초록 (Abstract)

니들-프리 제트 인젝터(needle-free jet injector)는 빠르고 통증이 적은 약물 전달 기술로
주목받고 있으나, 목표 깊이에 대한 일관된 침투를 확보하는 데에는 여전히 한계가 있다. 제트
침투 거동은 제형의 유변학적 특성과 조직의 생체역학적 특성이 복합적으로 작용해 결정되므로,
이를 통합적으로 규명하는 실험적 접근이 필요하다. 본 연구에서는 젤라틴 기반 피부 모사
하이드로겔과 대표 제형(글리세롤, 카복시메틸셀룰로오스(CMC), 소 혈청 알부민(BSA))을
이용하여 점도 및 전단 거동이 NFJI 성능에 미치는 영향을 체계적으로 평가하였다. 제트 직경,
속도, 정체압(stagnation pressure) 등 정량적 제트/유동 지표를 침투 깊이 및 측방 분산과 연계해
분석하였다. 또한 광학적 클리어링을 적용한 ex vivo 돼지 피부에서 마이크로초 시간 해상도의
근적외선(NIR) 이미징을 통해 제트–조직 상호작용의 과도(transient) 거동을 실시간으로
가시화하였다. 환자 및 해부학적 부위에 따른 조직 생체역학적 편차를 반영하기 위해
DermaLab® 탄성 측정 시스템으로 인체 피부의 탄성 및 점탄성을 다부위에서 측정하여 대표
탄성률(Young’s modulus) 범위를 정의하고, 이에 대응하는 젤라틴 팬텀을 제작하여 매질 강성의
영향을 통제된 조건에서 검증하였다. 그 결과, 매질 탄성률이 증가할수록 증류수, 글리세롤,
CMC 제형 모두에서 침투 깊이가 유의하게 감소하였으며, 이는 고정 압력 운용만으로는 다양한
조직 조건에서 일정한 침투 깊이를 보장하기 어렵다는 점을 시사한다. 이를 바탕으로, 스마트폰
기반 출력이 가능한 IoT 연동 NIR 반사형 흡입 장치로 현장 탄성률을 추정하고, 압력 조절형
공압식 인젝터와 결합한 피부 강성 반응형 NFJI 플랫폼을 구현하였다. 침투 깊이는 압력–탄성률
비(P/E)와 강한 상관관계를 보였고, 측정된 조직 탄성률로부터 목표 깊이에 필요한 최적 압력
설정값을 도출할 수 있었다. 검증 실험에서 고정 압력(0.5–3 MPa) 운용은 침투 깊이
변동계수(CV)가 14–17%였으나, P/E 기반 제어 주입은 CV 를 약 6%로 감소시켜 강성 조건
변화에 대한 주입 일관성을 크게 향상시켰다. 본 연구는 유변학 및 생체역학 정보를 결합한 NFJI
설계·운용의 정량적 기반을 제시하며, 향후 제형 유변학과 피부 탄성률을 동시에 반영하는
실시간 폐루프 제어로 확장 가능함을 보여준다.

다국어 초록 (Multilingual Abstract)

Development of Skin Stiffness-responsive Needle-free Injector Jakir Hossain Imran Department of Mechanical Engineering The Graduate School Kookmin University Needle-free jet injectors (NFJIs) offer a promising route for rapid, pain-free drug delivery, yet achieving consistent and depth-targeted penetration remains challenging. Jet penetration dynamics is jointly governed by the interplay between formulation rheology and tissue biomechanics, necessitating an integrated experimental approach. In this study, we systematically investigated how fluid viscosity and shear behavior influence NFJI performance using a gelatin-based hydrogel skin model and representative formulations including glycerol, carboxymethylcellulose (CMC), and bovine serum albumin (BSA). Quantitative jet and flow descriptors—such as jet diameter, velocity, and stagnation pressure—were correlated with jet penetration depth and dispersion characteristics. To better mimic physiological conditions, jet penetration and lateral dispersion were directly visualized in optically cleared ex vivo porcine skin using near-infrared (NIR) imaging with microsecond temporal resolution, enabling real-time observation of transient jet-tissue interactions. Recognizing that patient- and site- dependent biomechanics critically modulate injection outcomes, human skin elasticity and viscoelasticity were mapped across multiple anatomical locations using a DermaLab® elasticity probe to define representative skin stiffness ranges. Corresponding gelatin phantoms were prepared to match these elastic moduli, enabling controlled investigation of medium stiffness effects. Results revealed that increasing medium elastic modulus systematically reduced penetration depth for distilled water, glycerol, and CMC formulations, highlighting the need for adaptive, biomechanics-aware injection control rather than fixed-pressure operation. Building on these findings, we developed a skin-stiffness– responsive NFJI platform that integrates an IoT-enabled, NIR-reflection–based suction device for in situ elastic-modulus sensing (with smartphone readout) and a pressure-tunable, air-powered injector. Penetration depth exhibited a strong correlation with the pressure-to-elasticity ratio (P/E), allowing the measured tissue stiffness to be converted into an optimal pressure setpoint for depth-targeted delivery. Validation experiments demonstrated markedly improved consistency across elasticity conditions: while fixed-pressure operation (0.5–3 MPa) yielded penetration-depth coefficients of variation (CVs) of 14–17%, P/E-controlled injection reduced the CV to ~6%. These results establish a quantitative foundation for coupling rheological and biomechanical parameters in NFJI design and operation. Future investigations can extend this framework toward closed-loop control systems capable of autonomously adjusting jet parameters in real time according to both skin stiffness and formulation rheology, thereby advancing truly personalized, needle-free drug delivery. Keywords: Needle-free jet injector, formulation rheology, skin elasticity (elastic modulus), IoT-enabled stiffness sensing, personalized drug delivery.

목차 (Table of Contents)

• 1. Introduction 1
• 1.1 Background 1
• 1.2 Objective of the Study 4
• 1.3 Research Contributions 4
• 2. Influence of Drug Viscosity on Needle‑free Jet Injection Performance 5
• 2.1 Materials and Methods 5
• 2.1.1 Injection Device and Syringe 5
• 2.1.2 Materials Used and Their Characterizations 6
• 2.1.3 Stability Assessment of BSA After Injection 8
• 2.1.4 Imaging Setup for Gelatin Hydrogel Experiments 9
• 2.1.5 Visualization of NFJI Profiles in Porcine Skin Tissue 9
• 2.1.6 Sample Preparation for Ex-vivo Porcine Skin 11
• 2.2 Results and Discussion 11
• 2.2.1 Rheological Characterization of Model Injection Fluids 11
• 2.2.2 Impulse-Force Characterization of Newtonian and Non-Newtonian Fluids 13
• 2.2.3 Microjet Stagnation Pressure and Velocity 14
• 2.2.4 Penetration Performance in Skin-Mimicking Gel Models 16
• 2.2.5 Role of Reynolds and Weber Numbers in jet Penetration and Dispersion 17
• 2.2.6 Post-injection Stability Assessment of BSA 19
• 2.2.7 Rheology-Dependent Jet Diameter in NFJI 23
• 2.2.8 Penetration Dynamics in Cleared Porcine Tissue 24
• 2.2.9 Influence of Rheological Parameters on Penetration Depth in Porcine 26
• 3. Skin Stiffness Mapping and Stiffness-responsive NFJI Development 27
• 3.1 Anatomical Variations in Skin Stiffness and Their Effects on NFJI Outcomes 28
• 3.1.1 Materials and Methods 28
• 3.1.1.1 Assessment of Skin Mechanical Properties 28
• 3.1.2 Results and Discussion 29
• 3.1.2.1 Site-specific Skin Mechanics and NFJI in Gelatine Hydrogels 30
• 3.1.2.2 Effect of Gelatin Elastic Modulus on Jet Penetration Behaviour 31
• 3.2 Prototype and Theoretical Framework for a Skin stiffness–responsive NFJI 33
• 3.2.1 Materials and Methods 33
• 3.2.1.1 Design and Development of the Elasticity Measurement Device 33
• 3.2.1.2 Edge-Based Data Processing and Visualization Architecture 34
• 3.2.1.3 Calibration of NIR Sensor Output to Skin Deformation 36
• 3.2.1.4 Signal Processing for Quantification of Reflectance Changes 37
• 3.2.1.5 Multi-layer Monti Carlo simulation of NIR Reflectance Across Skin Types 38
• 3.2.1.6 Skin Elasticity Measurement Using Plate Theory 40
• 3.2.1.7 Needle-Free Injector Design and Penetration Depth Analysis 41
• 3.2.2 Results and Discussion 43
• 3.2.2.1 Relationship Between ΔR and ΔH 43
• 3.2.2.2 Baseline Stability 44
• 3.2.2.3 Monte Carlo Simulation Result 44
• 3.2.2.4 Validation of Skin Elasticity Measurement 46
• 3.2.2.5 NFJI Characterization 48
• 3.2.2.6 Penetration-Depth Model as a Function of Medium Elastic Modulus 49
• 3.2.2.7 Validation of P/E Model 50
• 4. Conclusion 52
• References 53