Guangli Liu

Photopolymerization of complex emulsions with irregular shapes fabricated by multiplex coaxial flow focusing

We fabricate complex emulsions with irregular shapes in the microscale by a simple but effective multiplex coaxial flow focusing process. A multiphase cone-jet structure is steadily formed, and the compound liquid jet eventually breaks up into Janus microdroplets due to the perturbations propagating along the jet interfaces. The microdroplet shapes can be exclusively controlled by interfacial tensions of adjacent phases. Crescent-moon-shaped microparticles and microcapsules with designated structural characteristics are further produced under ultraviolet light of photopolymerization after removing one hemisphere of the Janus microdroplets. These complex emulsions have potential applications in bioscience, food, functional materials, and controlled drug delivery.

Fabrication of a multilayer tissue-mimicking phantom with tunable optical properties to simulate vascular oxygenation and perfusion for optical imaging technology

Vast research has been carried out to fabricate tissue-mimicking phantoms, due to their convenient use and ease of storage, to assess and validate the performance of optical imaging devices. However, to the best of our knowledge, there has been little research on the use of multilayer tissue phantoms for optical imaging technology, although their structure is closer to that of real skin tissue. In this work, we design, fabricate, and characterize multilayer tissue-mimicking phantoms, with a morphological mouse ear blood vessel, that contain an epidermis, a dermis, and a hypodermis. Each tissue-mimicking phantom layer is characterized individually to match specific skin tissue layer characteristics. The thickness, optical properties (absorption coefficient and reduced scattering coefficient), oxygenation, and perfusion of skin are the most critical parameters for disease diagnosis and for some medical equipment. These phantoms can be used as calibration artifacts and help to evaluate optical imaging technologies.

Simulating tissue oxygenation by encapsulating hemoglobin in polymer microcapsules (Conference Presentation)

We describe a combination of liquid-jet microencapsulation and molding techniques to fabricate tissue-simulating phantoms that mimick functional characteristics of tissue oxygen saturation (StO2). Chicken hemoglobin (Hb) was encapsulated inside a photocurable resin by a coaxial flow focusing process. The microdroplets were cured by ultraviolet (UV) illumination to form Hb loaded polymersome microdroplets. The microdroplets were further freeze-dried to form semipermeable solid microcapules with an outer transparent polymeric shell and an inner core of Hb. The diameter of the microcapsules ranged from 50 to100 μm. The absorption spectrum of the microcapsules was measured by a UV/VIS spectrophotometer over a wavelength range from 400 nm to 1100 nm. To fabricate the tissue-simulating phantom, the Hb loaded microcapsules were dispersed in transparent polydimethylsiloxane (PDMS). The optical properties of the phantom were determined by an vertical double integrating sphere with a reconstruction algorithm. The experimental results showed that the tissue-simulating phantom exhibited the spectral characteristics closely resembling that of oxy-hemoglobin. The phantom had a long-term optical stability when stored in 4 ℃, indicating that microencapsulation effectively protected Hb and improved its shelf time. With the Hb loaded microcapsules, we will produce skin-simulating phantoms for quantitative validation of multispectral imaging techniques. To the best of the authors’ knowledge, no solid phantom is able to mimick living tissue oxygenation with good agreement. Therefore, our work provided an engineering platform for validating and calibrating spectral optical devices in biomedical applications.

3D printing of microtube in solid phantom to simulate tissue oxygenation and perfusion (Conference Presentation)

Tissue-simulating phantoms with interior vascular network may facilitate traceable calibration and quantitative validation of many medical optical devices. However, a solid phantom that reliably simulates tissue oxygenation and blood perfusion is still not available. This paper presents a new method to fabricate hollow microtubes for blood vessel simulation in solid phantoms. The fabrication process combines ultraviolet (UV) rapid prototyping technique with fluid mechanics of a coaxial jet flow. Polydimethylsiloxane (PDMS) and a UV-curable polymer are mixed at the designated ratio and extruded through a coaxial needle device to produce a coaxial jet flow. The extruded jet flow is quickly photo-polymerized by ultraviolet (UV) light to form vessel-simulating solid structures at different sizes ranging from 700 m to 1000 m. Microtube structures with adequate mechanical properties can be fabricated by adjusting material compositions and illumination intensity. Curved, straight and stretched microtubes can be formed by adjusting the extrusion speed of the materials and the speed of the 3D printing platform. To simulate vascular structures in biologic tissue, we embed vessel-simulating microtubes in a gel wax phantom of 10 cm x10 cm x 5 cm at the depth from 1 to 2 mm. Bloods at different oxygenation and hemoglobin concentration levels are circulated through the microtubes at different flow rates in order to simulate different oxygenation and perfusion conditions. The simulated physiologic parameters are detected by a tissue oximeter and a laser speckle blood flow meter respectively and compared with the actual values. Our experiments demonstrate that the proposed 3D printing process is able to produce solid phantoms with simulated vascular networks for potential applications in medical device calibration and drug delivery studies.

Stress stiffened silicon nitride micro bridges array as substrate with tunable stiffness for cell culture

Recently, interactions between one-dimensional structural stiffness of physical micro environments and cell biological process have been widely studied. However in previous studies, the influence of structural stiffness on biological process was coupled with the influence of micro fiber curvature. Therefore decoupling the influences of fiber curvature and structural stiffness on cell biological process is of prime importance. In this study, we proposed a novel cell culture substrate comprised of silicon nitride bridges whose structure stiffness can be regulated by altering the axial residual stress without changing material and geometry properties. Both theoretical calculations and finite element simulations were performed to study the influence of residual stress on structure stiffness of bridges. Then multi-positions AFM bending tests were implemented to measure local stiffness of a single micro bridge so as to verify our predictions. NIH/3T3 mouse fibroblast cells were cultured on our substrates to examine the feasibility of the substrate application for investigating cellular response to microenvironment with variable stiffness. The results showed that cells on the edge region near bridge ends were more spread, elongated and better aligned along the bridge axial direction than those on the bridge center region. The results suggest that cells can sense and respond to the differences of stiffness and stiffness gradient between the edge and the center region of the bridges, which makes this kind of substrates can be applied in some biomedical fields, such as cell migration and wound healing.

Optical characterization of tissue mimicking phantoms by a vertical double integrating sphere system

Accurate characterization of absorption and scattering properties for biologic tissue and tissue-simulating materials enables 3D printing of traceable tissue-simulating phantoms for medical spectral device calibration and standardized medical optical imaging. Conventional double integrating sphere systems have several limitations and are suboptimal for optical characterization of liquid and soft materials used in 3D printing. We propose a vertical double integrating sphere system and the associated reconstruction algorithms for optical characterization of phantom materials that simulate different human tissue components. The system characterizes absorption and scattering properties of liquid and solid phantom materials in an operating wavelength range from 400 nm to 1100 nm. Absorption and scattering properties of the phantoms are adjusted by adding titanium dioxide powder and India ink, respectively. Different material compositions are added in the phantoms and characterized by the vertical double integrating sphere system in order to simulate the human tissue properties. Our test results suggest that the vertical integrating sphere system is able to characterize optical properties of tissue-simulating phantoms without precipitation effect of the liquid samples or wrinkling effect of the soft phantoms during the optical measurement.

Effect of surface topographic features on the optical properties of skin: a phantom study

Tissue-simulating phantoms are used to validate and calibrate optical imaging systems and to understand light transport in biological tissue. Light propagation in a strongly turbid medium such as skin tissue experiences multiple scattering and diffuse reflection from the surface. Surface roughness introduces phase shifts and optical path length differences for light which is scattered within the skin tissue and reflected from the surface. In this paper, we study the effect of mismatched surface roughness on optical measurement and subsequent determination of optical properties of skin tissue. A series of phantoms with controlled surface features and optical properties corresponding to normal human skin are fabricated. The fabrication of polydimethylsiloxane (PDMS) phantoms with known surface roughness follows a standard soft lithography process. Surface roughness of skin-simulating phantoms are measured with Bruker stylus profiler. The diffuse reflectance of the phantom is validated by a UV/VIS spectrophotometer. The results show that surface texture and roughness have considerable influence on the optical characteristics of skin. This study suggests that surface roughness should be considered as an important contributing factor for the determination of tissue optical properties.

3D printing of tissue-simulating phantoms for calibration of biomedical optical devices

Clinical utility of many biomedical optical devices is limited by the lack of effective and traceable calibration methods. Optical phantoms that simulate biological tissues used for optical device calibration have been explored. However, these phantoms can hardly simulate both structural and optical properties of multi-layered biological tissue. To address this limitation, we develop a 3D printing production line that integrates spin coating, light-cured 3D printing and Fused Deposition Modeling (FDM) for freeform fabrication of optical phantoms with mechanical and optical heterogeneities. With the gel wax Polydimethylsiloxane (PDMS), and colorless light-curable ink as matrix materials, titanium dioxide (TiO2) powder as the scattering ingredient, graphite powder and black carbon as the absorption ingredient, a multilayer phantom with high-precision is fabricated. The absorption and scattering coefficients of each layer are measured by a double integrating sphere system. The results demonstrate that the system has the potential to fabricate reliable tissue-simulating phantoms to calibrate optical imaging devices.