The PI's research focuses on the development of innovative biomaterials, biosensing platforms, and translational biomedical systems for applications in tissue engineering, disease modeling, drug screening, and precision medicine. Major research topics are summarized as follows.

Collagen Liquid Crystal Elastomers for Bone Biomimetic Materials and Bone-on-a-Chip Development (NSTC 112-2314-B-309-001)

Taking advantage of the versatility and stimuli-responsiveness of collagen-based liquid crystal elastomer (LCE) hydrogel synthesized by the amine‒acrylate click chemistry of aza-Michael addition, this study aims at establishing bone-on-a-chip and osteoporosis-on-a-chip microfluidic systems with three-dimensional (3D) osteoblast/osteoclast co-culture to create a bone-stimulating microenvironment that mimics normal bone tissue as well as to construct an in vitro human disease model for osteoporosis. The 3D osteoblast/osteoclast co-culture is developed by co-culturing human bone marrow-derived mesenchymal stem cells (hBMSCs) with human CD14+ monocytes on collagen-based LCE hydrogel, which is integrated into a microfluidic system to establish a bone-on-a-chip platform mimicking the microenvironment of bone tissue in the presence of interstitial fluid flow. The bone-on-a-chip microfluidic device enables mechanical stimuli from the environment, such as surface stiffness and fluid shear stress, and the correlation of mechanotransduction with osteogenic differentiation on collagen-based LCE hydrogel to be investigated. On the other hand, collagen-based LCE hydrogel is stimuli-responsive to cell‒matrix interaction or cell-mediated matrix remodeling, such as the synthesis of extracellular matrix and mineral deposition during osteogenic differentiation both in the presence and absence of fluid shear stress, allowing novel biosensing functionalities unachievable with conventional bone scaffolds or biomaterials to be built into the bone-on-a-chip platform to signal the growth and differentiation status of the 3D osteoblast/osteoclast co-culture. Furthermore, we propose to transform the bone-on-a-chip platform into an in vitro human disease model of osteoporosis-on-a-chip featuring both the structure and microenvironment of the osteoporotic bone by synthesizing porous collagen-based LCE hydrogel to support 3D osteoblast/osteoclast co-culture in an osteoclastogenic state, followed by validation with FDA-approved bone anabolics to assess its efficacy and limitations. The microfluidic bone-on-a-chip and osteoporosis-on-a-chip models developed with collagen-based LCE hydrogel are considered promising platforms as alternatives to animal testing for future application in precision medicine for drug treatment and disease modeling customized to the patient.

Liquid Crystal Biosensors for Cancer Biomarker Immunodetection and Quantitative Protein Analysis (MOST 106-2314-B-309-001; 109-2320-B-309-001; 110-2320-B-309-001)

As the liquid crystal display (LCD) market becomes increasingly saturated and faces strong competition from emerging display technologies such as OLED and MicroLED, the applications of liquid crystal materials have become more diversified. This trend calls for broader interdisciplinary collaboration to develop new products and markets, one promising direction being the development of biomedical sensing technologies. At present, most liquid crystal-based biosensing methods rely on qualitative analysis through observation of liquid crystal optical textures and therefore lack precise quantitative capability. In addition, most liquid crystal biosensing techniques reported in the literature employ thermotropic liquid crystals as the sensing medium, among which the nematic liquid crystal 5CB (4-cyano-4′-pentylbiphenyl) is the most widely used.

To expand the applications of liquid crystals in biosensing, this research has continuously developed different types of thermotropic liquid crystals and liquid crystal phases as sensing media for biosensors, including cholesteric liquid crystals, blue-phase liquid crystals, dual-frequency liquid crystals, dye-doped liquid crystals, and liquid crystal–polymer composites. In recent years, to develop liquid crystal biosensors with real-time detection capability, the scope of sensing media has been further extended to lyotropic liquid crystals, particularly nematic lyotropic chromonic liquid crystals, as environmentally friendly and biocompatible sensing materials. By integrating transmission spectroscopy, haze measurement, dielectric spectroscopy, and electro-optical characterization of liquid crystals, this research has overcome the technical bottleneck that previously limited precise quantification in liquid crystal biosensing, and has developed label-free immunodetection techniques based on liquid crystals. In addition, by adopting strategies such as using liquid crystals with high birefringence, modifying alignment films, and applying electric fields, the sensitivity of liquid crystal-based biodetection has been significantly enhanced, thereby verifying the feasibility of liquid crystal-based immunodetection and quantitative protein analysis. This research has established a leading position internationally in biosensing at the liquid crystal–glass interface, providing an innovative direction for biomedical applications of liquid crystals and helping extend Taiwan’s strengths in liquid crystal display technology into the biomedical photonics and precision health industries.

Representative publications

1. M.-J. Lee**, J.-T. Hsieh, C.-T. Chang, Y.-C. Wu, P.-Y. Chan, C.‑M. Chien, and W. Lee*. 2026. Highly sensitive sunset yellow-based optical and dielectric biosensing of SARS-CoV-2 nucleocapsid protein in saliva. Colloids Surf. B Biointerfaces 257: 115128 (**first and corresponding author; SCIE, 7/79, Biophysics, 2024 IF 5.6).
2. T.-K. Chang#, Y.-Y. Tseng#, P.-C. Wu, M.-J. Lee*, and W. Lee*. 2023. Optical and flexoelectric biosensing based on a hybrid-aligned liquid crystal of anomalously small bend elastic constant. Biosens. Bioelectron. 232: 115314 (#The authors contributed equally to this work; *corresponding author; SCIE, 3/111, Chemistry, Analytical, 2024 IF 10.5).
3. H. Shaban, J.-T. Hsieh, M.-J. Lee*, and W. Lee*. 2023. Label-free optical and electrical immunoassays based on lyotropic chromonic liquid crystals: Implications of real-time detection and kinetic analysis. Biosens. Bioelectron. 223: 115011 (*corresponding author; SCIE, 3/111, Chemistry, Analytical, 2024 IF 10.5).
4. T.-K. Chang, P.-C. Tung, M.-J. Lee*, and W. Lee*. 2022. A liquid-crystal aptasensing platform for label-free detection of a single circulating tumor cell. Biosens. Bioelectron. 216: 114607 (*corresponding author; SCIE, 3/111, Chemistry, Analytical, 2024 IF 10.5).
5. B.-S. Chen, M.-J. Lee*, and W. Lee*. 2022. Multimodal spectrometric and dielectric biosensing with an ionic-surfactant-doped liquid crystal. Sens. Actuator B-Chem. 365: 131912 (*corresponding author; SCIE, 2/79, Instruments & Instrumentation, 2024 IF 7.7).
6. M.-J. Lee**, C.-P. Pai, P.-C. Wu, and W. Lee*. 2021. Label-free single-substrate quantitative protein assay based on optical characteristics of cholesteric liquid crystals. J. Mol. Liq. 331: 115756 (**first and corresponding author; SCIE, 6/39, Physics, Atomic, Molecular & Chemical, 2024 IF 5.2).
7. C.-M. Lin, P.-C. Wu, M.-J. Lee,* and W. Lee.* 2019. Label-free protein quantitation by dielectric spectroscopy of dual-frequency liquid crystal. Sens. Actuator B-Chem. 282: 158–163 (*corresponding author; SCIE, 2/79, Instruments & Instrumentation, 2024 IF 7.7).

Development of Osteoanabolic Drugs and Screening Platforms (MOST 101-2314-B-309-001-MY3; 105-2633-B-309-001; 106-2633-B-309-001)

This research addresses the limited availability and safety concerns of clinically used bone-stimulating drugs, some of which carry a risk of inducing bone cancer. Our work was the first to demonstrate that polyamine compounds can promote osteogenic differentiation of human bone marrow-derived mesenchymal stem cells by upregulating osteogenic gene expression while suppressing adipogenic gene expression. In parallel, an aptamer-based drug screening platform targeting sclerostin was developed to facilitate drug repurposing and accelerate the discovery of new bone-stimulating agents for bone metabolic disorders such as osteoporosis, for which effective therapies remain limited.

Representative publications

1. C.-C. Lee#, C.-C. Chuang#, C.-H. Chen, Y.-P. Huang, C-Y. Chang, P.-Y. Tung, and M.-J. Lee*. 2024. In vitro and in vivo studies on exogenous polyamines and a-difluoromethylornithine to enhance bone formation and suppress osteoclast differentiation. Amino Acids 56: 43 (#The authors contributed equally to this work; *corresponding author; SCIE, 227/320, Biochemistry and Molecular Biology, 2024 IF 2.4).
2. C.-C. Lee#, C.-M. Hung#, C.-H. Chen, Y.-C. Hsu, Y.-P. Huang, T.-B. Huang, and M.-J. Lee*. 2021. Novel aptamer-based small-molecule drug screening assay to identify potential sclerostin inhibitors against osteoporosis. Int. J. Mol. Sci. 22: 8320 (#The authors contributed equally to this work; *corresponding author; SCIE, 72/320, Biochemistry & Molecular Biology, 2024 IF 4.9).
3. Y. H. Tsai#, K. L. Lin#, Y. P. Huang, Y. C. Hsu, Y. Chen, M. H. Sie, G. J. Wang, and M. J. Lee*. 2015. Suppression of ornithine decarboxylase promotes osteogenic differentiation of human bone marrow-derived mesenchymal stem cells. FEBS Letters 589: 2058–2065 (#The authors contributed equally to this work; *corresponding author; SCIE, 27/79, Biophysics, 2024 IF 3.0).
4. M. J. Lee*, Y. Chen, Y. P. Huang, Y. C. Hsu, L. H. Chiang, T. Y. Chen and G. J. Wang. 2013. Exogenous polyamines promote osteogenic differentiation by reciprocally regulating osteogenic and adipogenic gene expression. J. Cell. Biochem. 114: 2718–2728 (*first and corresponding author; SCIE, 187/320, Biochemistry & Molecular Biology, 2024 IF 2.8).

Polyethylenimine-Functionalized Carbon Nanomaterials as Nonviral Gene Delivery Carriers (MOST 103-2633-B-309-001)

This research aims to develop carbon-based nanomaterials as non-integrating, nonviral gene delivery carriers to reduce the carcinogenic risks associated with viral vectors. The results demonstrated that polyethylenimine (PEI)-functionalized carbon nanotubes and graphene oxide can effectively deliver small interfering RNA (siRNA) into human cervical cancer cells and breast cancer cells, resulting in gene silencing and suppression of cancer cell migration. These findings support the potential application of novel nanobiomaterials in targeted cancer therapy and gene therapy.

Representative publications

1. Y. P. Huang, C. M. Hung, Y. C. Hsu, C. Y. Zhong, W. R. Wang, C. C. Chang, and M. J. Lee.* 2016. Suppression of breast cancer cell migration by small interfering RNA delivered by polyethylenimine-functionalized graphene oxide. Nanoscale Res. Lett. 11: 247.
2. Y. P. Huang, I. J. Lin, C. C. Chen, Y. C. Hsu, C. C. Chang, and M. J. Lee.* 2013. Delivery of small interfering RNAs in human cervical cancer cells by polyethylenimine-functionalized carbon nanotubes. Nanoscale Res. Lett. 8: 267.