Since 2014, Dr. Liu published 28 peer-reviewed articles with 1168 citations, hi-index 16, i10-index 23 (based on google scholar on June 24, 2013). He made substantial contributions in the fields of 3D single-particle tracking, biophysical biomarkers for cancer diagnosis, and biomaterials & tissue engineering. 

1. Inventions of 3D single-particle tracking techniques:

Dr. Liu and his colleagues developed an entirely new two-photon 3D tracking microscope named TSUNAMI (Tracking Single particles Using Nonlinear And Multiplexed Illumination). It can track particles at depths up to 200 μm in scattering samples with 22/90 [xy/z] nm spatial localization precision and millisecond temporal resolution. Related works have been published in Nature Communications, 2015 and Applied Physics Letters, 2015. This technique led to many applications in life science: monitoring epidermal growth factor receptor (EGFR) trafficking in tumor spheroids (Biophysical Journal, 2016)3, evaluating anti-PDL1 antibody-induced endocytosis (Cancer Cell, 2018)4, and phenotyping diseased muscle cells (Biomaterials, 2018)5. An advanced version of TSUNAMI was developed for dual-particle tracking (ACS Nano, 2020)6, which enables the visualization of particle rotation on the plasma membrane of living cells. The innovative technology allows the investigation of nanoparticle/virus-cell interactions. 

2. Invention of a new type of biophysical biomarkers for cancer diagnosis

As biophysical properties of tissues and cells play essential roles in cellular function, morphogenesis, and disease progression, numerous conventional techniques have been developed to characterize cells and differentiate benign cells from cancer cells. Dr. Liu invented a single-particle tracking-based biophysical phenotyping assay named “Transmembrane Receptor Dynamics (TReD)”. TReD can differentiate highly-invasive cancer cells from less-invasive or benign cells by measuring the dynamics of transmembrane receptors, such as EGFR. As a proof of concept, this method has been applied to a series of breast cancer cell lines and prostate cancer cell lines, and results demonstrated the metastatic potentials of cancer cells could be quantified by TReD (Scientific Reports, 2019; Cancers, 2019). Furthermore, the physical parameters extracted from EGFR dynamics are correlated with gene expression profiles and cell behaviors. The TReD phenotyping assay relies on an optical interrogation method (SPT on fluorescently tagged EGFRs), and it’s a contact-free technique that can probe the topography of the plasma membrane and nanostructure of the membrane-associated cytoskeleton with sub-diffraction limited resolution. Several physical science approaches can measure the mechanical properties of cancer cells, but direct contact probes are often needed (e.g., AFM or micropipette aspiration device). It makes these methods incompatible with microfluidic devices. In contrast, TReD is based on single-particle tracking that is entirely compatible with commercially available microfluidic devices, which enable the integration of TReD assay with circulating tumor cell capture platforms. We envision the TReD assay can be applied to liquid biopsy for the early detection of metastasis. Dr. Liu further elaborated its potential for gaining insights into biology and being translated as a cancer diagnostic tool based on machine learning models (Bioinformatics, 2022). 

3. Tissue engineering and cartilage regenerative medicine

Dr. Liu’s work in biomimetic scaffolds targets creating biofunctional constructs to recapitulate tissues. Methods of fabricating porous scaffolds using microfluidics were invented and granted with two US patents (US Patent 8,513,014, 2013; US Patent 9,957,481, 2018. Microfluidic chips were used to generate bubbles by mixing a gas and a liquid containing a cross-linkable material to produce a matrix of gas bubbles of substantially the same size and to cross-link the cross-linkable material to form a structure in which cells are grown. This highly ordered and interconnected scaffold is very suitable for tissue engineering, and it has demonstrated its feasibility in cartilage tissue engineering (Biomaterials 2012,  Biotechnology and Bioengineering 2014, Tissue Engineering Part A 2016) and lung tissue engineering (Biomaterials 2014). He also participated in clinical research on stem cell therapy for knee cartilage regeneration, and a nice-year follow-up demonstrated the therapeutic efficacy of bone marrow mesenchymal stem cell-derived chondrogenic precursors for repairing knee cartilage defects (Biomolecules 2021). A comparison of stem cell therapy and microfracture was completed, in which cell therapy provides sustainable efficacy better than microfracture (Polymers 2021).