# Bi-Chang Chen
Bi-Chang Chen is an optical microscopist working in Taiwan who develops and applies advanced fluorescence imaging methods, currently a Research Fellow and Deputy Director (2026–) at the Research Center for Applied Sciences (RCAS), [Academia Sinica](https://www.edgepedia.org/academia-sinica), known for co-developing lattice light-sheet microscopy as a postdoctoral associate in [Eric Betzig](https://www.edgepedia.org/eric-betzig)'s group at HHMI's Janelia Research Campus and honored with the 2015 AAAS Newcomb Cleveland Prize.[1](https://www.rcas.sinica.edu.tw/web/mem_faculty/Chen_BiChang_en.html) • [2](https://gims.tmu.edu.tw/Download.aspx?dir=News&file=73-9E-5C-51-FF-65-15-DE-B0-D1-3B-3E-08-5E-D7-14.pdf&filename=CV)
| Fact | Detail |
|---|---|
| Field | Lightsheet microscopy; super-resolution imaging of cleared and expanded tissues[1](https://www.rcas.sinica.edu.tw/web/mem_faculty/Chen_BiChang_en.html) |
| Training | B.S. and M.S. Chemistry, National Taiwan University (1997–2003); Ph.D. Chemistry, UT Austin (2006–2011)[1](https://www.rcas.sinica.edu.tw/web/mem_faculty/Chen_BiChang_en.html) |
| HHMI/Janelia | Postdoctoral Associate with Eric Betzig, 2011–2014, co-developing lattice light-sheet microscopy[1](https://www.rcas.sinica.edu.tw/web/mem_faculty/Chen_BiChang_en.html) • [2](https://gims.tmu.edu.tw/Download.aspx?dir=News&file=73-9E-5C-51-FF-65-15-DE-B0-D1-3B-3E-08-5E-D7-14.pdf&filename=CV) |
| Current position | Research Fellow (2025–) and Deputy Director (2026–), RCAS, Academia Sinica[1](https://www.rcas.sinica.edu.tw/web/mem_faculty/Chen_BiChang_en.html) |
| Signature publication | Lattice light-sheet microscopy, *Science* (2014); about 1,333 citations per iCite[3](https://pubmed.ncbi.nlm.nih.gov/25342811/) |
| Awards | 2015 AAAS Newcomb Cleveland Prize; 2020 Y. Z. Hsu Science Paper Award; 2021 Academia Sinica Early-Career Investigator Research Achievement Award[1](https://www.rcas.sinica.edu.tw/web/mem_faculty/Chen_BiChang_en.html) |
## Early life and education
Chen studied chemistry at National Taiwan University, completing a B.S. (1997–2001) and an M.S. (2001–2003); his master's thesis studied the morphology of mesoporous materials under Professor Chung-Yuan Mou.[1](https://www.rcas.sinica.edu.tw/web/mem_faculty/Chen_BiChang_en.html) • [2](https://gims.tmu.edu.tw/Download.aspx?dir=News&file=73-9E-5C-51-FF-65-15-DE-B0-D1-3B-3E-08-5E-D7-14.pdf&filename=CV) He then moved to the [University of Texas at Austin](https://www.edgepedia.org/university-of-texas-at-austin) for a Ph.D. in Chemistry (2006–2011), titled "Chemical Imaging with Coherent anti-Stokes Raman Scattering (CARS) Microscopy" under Professor Sang-Hyun Lim.[1](https://www.rcas.sinica.edu.tw/web/mem_faculty/Chen_BiChang_en.html) • [2](https://gims.tmu.edu.tw/Download.aspx?dir=News&file=73-9E-5C-51-FF-65-15-DE-B0-D1-3B-3E-08-5E-D7-14.pdf&filename=CV)
## Career
In summer 2011 Chen joined Eric Betzig's group at HHMI's Janelia Research Campus as a postdoctoral associate to develop lattice light-sheet microscopy, a project that ran through 2014.[1](https://www.rcas.sinica.edu.tw/web/mem_faculty/Chen_BiChang_en.html) • [2](https://gims.tmu.edu.tw/Download.aspx?dir=News&file=73-9E-5C-51-FF-65-15-DE-B0-D1-3B-3E-08-5E-D7-14.pdf&filename=CV) In April 2014 he returned to Taiwan as an Assistant Research Fellow at RCAS, Academia Sinica; he was promoted to Associate Research Fellow in April 2020 and to Research Fellow in 2025.[1](https://www.rcas.sinica.edu.tw/web/mem_faculty/Chen_BiChang_en.html) • [2](https://gims.tmu.edu.tw/Download.aspx?dir=News&file=73-9E-5C-51-FF-65-15-DE-B0-D1-3B-3E-08-5E-D7-14.pdf&filename=CV) He became Deputy Director of RCAS in 2026.[1](https://www.rcas.sinica.edu.tw/web/mem_faculty/Chen_BiChang_en.html) A note on the HHMI affiliation that appears in some databases: he was a postdoctoral associate there, not an HHMI investigator; his appointments since 2014 have been at Academia Sinica.[1](https://www.rcas.sinica.edu.tw/web/mem_faculty/Chen_BiChang_en.html)
## Research and contributions
**Lattice light-sheet microscopy.** The 2014 *Science* paper from the Betzig group crafted ultrathin light sheets from two-dimensional optical lattices, enabling 3D imaging of living specimens for hundreds of volumes, often at subsecond intervals, at the diffraction limit, and beyond, with low phototoxicity and multicolor, subcellular-resolution detection.[3](https://pubmed.ncbi.nlm.nih.gov/25342811/) • [2](https://gims.tmu.edu.tw/Download.aspx?dir=News&file=73-9E-5C-51-FF-65-15-DE-B0-D1-3B-3E-08-5E-D7-14.pdf&filename=CV) The demonstrated applications spanned four orders of magnitude in space and time: single transcription factor diffusion in stem cell spheroids, mitotic microtubule dynamics, the immunological synapse, neutrophil motility in a 3D matrix, and embryogenesis in *Caenorhabditis elegans* and *Drosophila melanogaster*.[3](https://pubmed.ncbi.nlm.nih.gov/25342811/)
**Single-molecule transcription factor imaging.** Chen's instrumentation fed directly into studies of gene regulation in embryonic stem cells. The 2014 *Cell* paper on Sox2/Oct4 enhanceosome assembly showed that assembly is hierarchically ordered, with Sox2 binding first and assisting Oct4, and that Sox2/Oct4 use a trial-and-error search: 84 to 97 three-dimensional diffusion events of 3.3–3.7 s, interspersed with brief nonspecific collisions of 0.75–0.9 s, before dwelling at specific target DNA for 12.0–14.6 s.[4](https://doi.org/10.1016/j.cell.2014.01.062) A companion eLife paper showed Sox2 enhancers form 3D clusters segregated from heterochromatin and overlapping a subset of Pol II enriched regions, with a 3D-diffusion-dominant search mode between clusters and chromatin-bound states within them.[5](https://doi.org/10.7554/eLife.04236)
**Extended-resolution structured illumination microscopy.** Conventional SIM typically gains only a twofold resolution improvement. The 2015 *Science* paper extended live-cell SIM in two ways: ultrahigh numerical aperture SIM at 84-nanometer lateral resolution for more than 100 multicolor frames, and nonlinear SIM with patterned activation at 45- to 62-nanometer resolution for roughly 20 to 40 frames, applied to clathrin and caveolin assemblies, Rab5a in early endosomes, α-actinin, mitochondria, actin, and the [Golgi apparatus](https://www.edgepedia.org/golgi-apparatus).[6](https://doi.org/10.1126/science.aab3500) Chen frames this work against the Abbe diffraction limit, λ/2(NA), noting that techniques such as STED, PALM, and STORM image below the roughly 200-nm lateral limit but are mostly restricted to 2D imaging of fixed or dead samples because of high laser power or slow localization.[7](https://remotesensing.spiedigitallibrary.org/profile/Bi-Chang.Chen-3290199)
**Biological applications at Janelia.** Using the new microscopes, Chen co-authored studies including the 2013 *Science* paper showing that a Wnt protein immobilized on a bead orients asymmetric stem cell division, with the Wnt-proximal daughter retaining pluripotency markers and the distal daughter differentiating.[8](https://doi.org/10.1126/science.1231077) The 2015 *Immunity* paper resolved the temporal order of cytotoxic T lymphocyte synapse maturation: cortical actin depletion and TCR clustering within 1 minute, granule clustering around the moving centrosome within 2.5 minutes, and granule arrival at the synapse after 6 minutes, identifying actin depletion as critical for secretion.[9](https://doi.org/10.1016/j.immuni.2015.04.013) In *C. elegans* embryos, the 2014 eLife study showed MEG-1 and MEG-3 are phosphorylated by MBK-2/DYRK and dephosphorylated by PP2A(PPTR-½); phosphorylation promotes P granule disassembly and dephosphorylation promotes assembly, showing these liquid-like granules are non-homogeneous, phosphorylation-regulated structures.[10](https://doi.org/10.7554/eLife.04591) A 2017 *Science* paper used lattice light-sheet plus quantum dot contact mapping to show [T cell](https://www.edgepedia.org/t-cell) microvilli survey the majority of an opposing surface within 1 minute, with TCR accumulation selectively stabilizing microvilli independent of tyrosine kinase signaling and the actin cytoskeleton.[11](https://doi.org/10.1126/science.aal3118)
**Imaging in cleared and expanded tissues.** At Academia Sinica, Chen developed lightsheet localization microscopy for clarified tissue and potassium acrylate expansion lightsheet microscopy, now applied to most model organisms with impact in neuroscience and developmental biology; his stated current goal is developing optical microscopy with electron-microscopy-level resolution in large tissue imaging.[1](https://www.rcas.sinica.edu.tw/web/mem_faculty/Chen_BiChang_en.html) • [2](https://gims.tmu.edu.tw/Download.aspx?dir=News&file=73-9E-5C-51-FF-65-15-DE-B0-D1-3B-3E-08-5E-D7-14.pdf&filename=CV)
## Key publications
**Lattice light-sheet microscopy: imaging molecules to embryos at high spatiotemporal resolution** (*Science*, 2014; doi:10.1126/science.1257998). This methods paper introduced ultrathin light sheets from 2D optical lattices and demonstrated fast, gentle 3D live imaging across systems from single molecules to whole embryos; it defined a new standard for long-duration, low-phototoxicity imaging.[3](https://pubmed.ncbi.nlm.nih.gov/25342811/)
**Single-molecule dynamics of enhanceosome assembly in embryonic stem cells** (*Cell*, 2014; doi:10.1016/j.cell.2014.01.062). Combined single-molecule imaging with [ChIP-exo](https://www.edgepedia.org/chip-exo) mapping to quantify how Sox2 and Oct4 search for and assemble on target DNA, quantifying the trial-and-error search in seconds and events.[4](https://doi.org/10.1016/j.cell.2014.01.062)
**Extended-resolution structured illumination imaging of endocytic and cytoskeletal dynamics** (*Science*, 2015; doi:10.1126/science.aab3500). Pushed live-cell SIM to 84 nm and, with patterned activation, 45–62 nm lateral resolution, extending nanoscale imaging to living cells.[6](https://doi.org/10.1126/science.aab3500)
**Regulation of RNA granule dynamics by phosphorylation of serine-rich, intrinsically disordered proteins in C. elegans** (*eLife*, 2014; doi:10.7554/eLife.04591). Identified phosphorylation as the switch controlling P granule assembly and disassembly in live embryos, imaged by lattice light-sheet microscopy.[10](https://doi.org/10.7554/eLife.04591)
**A localized Wnt signal orients asymmetric stem cell division in vitro** (*Science*, 2013; doi:10.1126/science.1231077). Showed that a spatially restricted Wnt signal alone can orient division and generate distinct daughter cell fates at predictable positions relative to the source.[8](https://doi.org/10.1126/science.1231077)
**Actin depletion initiates events leading to granule secretion at the immunological synapse** (*Immunity*, 2015; doi:10.1016/j.immuni.2015.04.013). Resolved the minute-by-minute sequence of synapse maturation in 4D and established actin depletion as a prerequisite for secretion.[9](https://doi.org/10.1016/j.immuni.2015.04.013)
**Visualizing dynamic microvillar search and stabilization during ligand detection by T cells** (*Science*, 2017; doi:10.1126/science.aal3118). Defined how T cell microvilli scan antigen-presenting cell surfaces within a minute and how TCR engagement selectively stabilizes them.[11](https://doi.org/10.1126/science.aal3118)
**3D imaging of Sox2 enhancer clusters in embryonic stem cells** (*eLife*, 2014; doi:10.7554/eLife.04236). Mapped the 3D organization of Sox2 enhancers in living nuclei and linked it to local-versus-global transcription factor search behavior.[5](https://doi.org/10.7554/eLife.04236)
## By the numbers
- About 1,333 citations for the 2014 lattice light-sheet *Science* paper per iCite; an aggregator reports 2,092, so the count depends on the citation database.[3](https://pubmed.ncbi.nlm.nih.gov/25342811/)
- 84 nm and 45–62 nm lateral resolution achieved in live cells with extended SIM.[6](https://doi.org/10.1126/science.aab3500)
- 84–97 three-dimensional diffusion events (3.3–3.7 s each) before Sox2/Oct4 commit to specific DNA, with dwell times of 12.0–14.6 s.[4](https://doi.org/10.1016/j.cell.2014.01.062)
- Granule arrival at the immunological synapse 6 minutes after contact, following actin depletion within 1 minute.[9](https://doi.org/10.1016/j.immuni.2015.04.013)
## Honours and recognition
Chen received the 2015 AAAS Newcomb Cleveland Prize, the 2020 18th Y. Z. Hsu Science Paper Award in the Optoelectronics Science & Technology Category, and the 2021 Academia Sinica Early-Career Investigator Research Achievement Award.[1](https://www.rcas.sinica.edu.tw/web/mem_faculty/Chen_BiChang_en.html) His appointment as RCAS Deputy Director in 2026 marks an administrative role alongside his research.[1](https://www.rcas.sinica.edu.tw/web/mem_faculty/Chen_BiChang_en.html)
## References
1. [RCAS: Bi-Chang Chen (Academia Sinica, Research Center for Applied Sciences)](https://www.rcas.sinica.edu.tw/web/mem_faculty/Chen_BiChang_en.html)
2. [Bi-Chang Chen CV (Taipei Medical University GIMS)](https://gims.tmu.edu.tw/Download.aspx?dir=News&file=73-9E-5C-51-FF-65-15-DE-B0-D1-3B-3E-08-5E-D7-14.pdf&filename=CV)
3. [Lattice light-sheet microscopy: imaging molecules to embryos at high spatiotemporal resolution (Science, 2014)](https://pubmed.ncbi.nlm.nih.gov/25342811/)
4. [Single-molecule dynamics of enhanceosome assembly in embryonic stem cells (Cell, 2014)](https://doi.org/10.1016/j.cell.2014.01.062)
5. [3D imaging of Sox2 enhancer clusters in embryonic stem cells (eLife, 2014)](https://doi.org/10.7554/eLife.04236)
6. [Extended-resolution structured illumination imaging of endocytic and cytoskeletal dynamics (Science, 2015)](https://doi.org/10.1126/science.aab3500)
7. [Dr. Bi-Chang Chen Profile (SPIE Digital Library)](https://remotesensing.spiedigitallibrary.org/profile/Bi-Chang.Chen-3290199)
8. [A localized Wnt signal orients asymmetric stem cell division in vitro (Science, 2013)](https://doi.org/10.1126/science.1231077)
9. [Actin depletion initiates events leading to granule secretion at the immunological synapse (Immunity, 2015)](https://doi.org/10.1016/j.immuni.2015.04.013)
10. [Regulation of RNA granule dynamics by phosphorylation of serine-rich, intrinsically disordered proteins in C. elegans (eLife, 2014)](https://doi.org/10.7554/eLife.04591)
11. [Visualizing dynamic microvillar search and stabilization during ligand detection by T cells (Science, 2017)](https://doi.org/10.1126/science.aal3118)
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*Topic: Encyclopedia › Physical world and mathematics › Physical and mathematical scientists › Physicists and astronomers › Researchers in applied physics, optics, photonics, and plasma physics › Biophotonics and optical imaging*
*Initially written Sep 17, 2026 · Edited: Oct 11, 2026; Oct 15, 2026*
*Copyright 2026 EdgeChat AI, a subsidiary of Biostate AI.*
License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license