Following completion of a Ph.D. at the University of Cambridge, UK, 2004, Shuang Fang Lim served in a postdoctoral Research Position at Princeton University from 2004-2008. Her work there focused on upconverting nanoparticlels (UCNPs) and the synthesis, photophysics and bio-applications of nanoparicles. Following this assignment, she then served as in a postdoctoral position for one year at NC State University and then in a Research Assistant professor position for three years before accepting an Assistant Professor appointment staring in the fall of 2012.
Lim's research is centered on the synthesis, characterization, photophysics, bioconjugation, and application of UCNPs. These UCNPs are developed for applications as biosensors in microarrays and as biotherapeutics in photodynamic and photothermal therapy. UCNPs are excited in the near infrared (NIR) and emit fluorescence in the visible spectrum, offer superior photostability, and high signal-to-noise ratio for imaging biological samples due to zero tissue autofluorescence. These properties make UCNPs ideal for 3D imaging and monitoring of biological processes over long time durations. The upconversion mechanism in UCNPs is based on either sequential excitation of the same emitting center in singly doped rare upconverters, called APTE (addition de photon par transferts d’energie), or excitation of two centers and subsequent energy transfer in co-doped rare earth upconverters, known as the ETU (energy transfer upconversion) effect. Fluorescence transition from the higher excited state to the ground state leads to fluorescence which is observed as anti-Stokes emission, whereby the emitted photon is higher in energy than the excitation energy. The large penetration depth of the NIR excitation and low background of multi-photon fluorescence, and active targeting, establishes these nanomaterials as ideal 3D diagnostic probes. UCNPs have been used in point-of-care diagnostics (POC) such as in lateral flow assays, array-in-well assays and in microarray assays.
She also works on single molecule epigenetic mapping of DNA and chromatin. In the nuclei of eukaryotic cells, genomic DNA is packaged as chromatin. The fundamental repeating unit of chromatin is the nucleosome, which is the complex formed when double-stranded DNA wraps around a histone octamer made of a central H3/H4 tetramer. Each of these 4 types of core histone (H2A, H2B, H3, H4) has a flexible amino acid tail of 25–40 residues, known as a histone tail. Common histone tail covalent modifications, such as acetylation, mono-,di-, and tri-methylation, phosphorylation, and ubiquitination function to modulate the higher-order structure of chromatin. Some modifications can be inherited between cell generations, and are thus epigenetic marks, such as the methylation state of some genes, which can be used as a biomarker for tumorogenesis. Her efforts are concentrated on techniques to identify specific methylation and acetylation markers at genomic resolution.
Enhancement of Upconverted Fluorescence by Interference Layers
J. Wirth, K. K. Green, M. O'Connor, S. F. Lim,
Small, 13(6), (Dec 2016), 1602846
Nanoplasmonic Upconverting Nanoparticles as Orientation Sensors for Single Particle Microscopy
K. Green, J. Wirth, S. F. Lim,
Scientific Reports, 7, (Apr 2016), 762
Optical investigation of gold shell enhanced 25 nm diameter upconverted fluorescence emission
K. Green, J. Wirth, S. F. Lim,
Nanotechnology, 27(13), (2016), 135201
Interference of ATP with the fluorescent probes YOYO-1 and YOYO-3 modifies the mechanical properties of intercalator-stained DNA confined in nanochannels
M. Roushan, Z. Azad, S. F. Lim, H. Wang, R. Riehn,
Microchimica Acta, 182(7-8), (Jun 2015), 1561-1565
Enhancement of single particle rare earth doped NaYF4: Yb, Er emission with a gold shell
L. Li, K. Green, H. Hallen, S. F. Lim,
Nanotechnology, 26 (2), (Jan 2015), 025101/1-9
Upconverting nanoparticle based multi-functional nanoplatform for enhanced photodynamic therapy: Promises and Perils
S.F. Lim and R. H. Austin. In M. R. Hamblin and P. Avci (eds.)
Applications of Nanoscience in Photomedicine Woodhead Publishing Series in Biomedicine, (Aug 2014)
Probing transient protein-mediated DNA linkages using nanoconfinement.
M. Roushan, P. Kaur, A. Karpusenko, P. J. Countryman, C. P. Ortiz, S. F. Lim, H. Wang, R. Riehn,
Biomicrofluidics, 8(3), (2014), 034113/1-15
Chromatin modification mapping in nanochannels.
S. F. Lim, A. Karpusenko, D.E. Streng, R. Riehn,
Biomicrofluidics, 7 (6), (Nov 2013), 064105/1-8
Fluctuation modes of nanoconfined DNA.
A. Karpusenko, J. H. Carpenter, C. , S. F. Lim, J. Pan, R. Riehn,
Journal of Applied Physics, 111(2), (Jan 2012), 024701-024708
Near-field enhanced ultraviolet resonance Raman spectroscopy using aluminum bow-tie nano-antenna.
L. Li, S. F. Lim, A. A. Puretzky, R. Riehn, H. D. Hallen,
Applied Physics Letters, 101(11), (Sep 2012), 113116/1-4
DNA Methylation Profiling in Nanochannels.
S. F. Lim, A. Karpusenko, J. J. Sakon, J. A. Hook, T. A. Lamar, R. Riehn,
Biomicrofluidics, 5(3), (Jul 2011), 034106-034114
Density fluctuations dispersion relationship for a polymer confined to a nanotube.
J. H. Carpenter, A. Karpusenko, J. Pan, S. F. Lim, R. Riehn,
Applied Physics Letters, 98(25), (Jun 2011), 253704-253706
Epigenetic Analysis of Chromatin in Nanochannels.
D. E. Streng, S. F. Lim, R. Riehn,
Biophysical Journal, 98(3), (Jan 2010), 600A-600A
Particle size dependence of the dynamic photophysical properties of NaY4, Yb, Er nanocrystals.
S. F. Lim, W. S. Ryu, R. H. Austin,
Optics Express, 18(3), (Feb 2010), 2309-2316
Nanofabricated upconversion nanoparticles for photodynamic therapy.
B. Ungun, R. K. Prud'homme, S. J. Budijono, J. Shan, S. F. Lim, Y. Ju, R. H. Austin,
Optics Express, 17(1), (Jan 2009), 80-86
Stretching chromatin through confinement
D. E. Streng , S. F. Lim , J. Pan , A. Karpusenka, R. Riehn,
Lab Chip, 9, (Aug 2009), 2772 - 2774
Upconverting nanophosphors for bioimaging
S. F. Lim, R. Riehn, C-K Tung, W. S. Ryu, R. Zhuo, J. Dalland, R. H. Austin,
Nanotechnology, 20(40), (Sep 2009), 405701
The Sackler Colloqium on Promise and Perils In Nanotechnology for Medicine.
R. H. Austin, S. F. Lim,
PNAS, 105(45), (Nov 2008), 17217-1722
Nanochannels for Genomic DNA Analysis, The Long and the Short of It
R. Riehn, W. Reisner, J. O. Tegenfeldt, Y. M. Wang, C. -K. Tung, S. F. Lim, E. C. Cox, J. C. Sturm, K. Morton, S. Y. Chou, R. H. Austin. in Liu, R.H. and Lee, A.P. (eds.)
Integrated Biochips for DNA Analysis, Landes Bioscience, Austin, TX and Springer Science+Business Media, New York, NY, (2007), pgs 151-186
In vivo and scanning electron microscopy imaging of upconverting nanophosphors in Caenorhabditis elegans.
S. F. Lim, R. Riehn, W. S. Ryu, N. Khanarian, C. K. Tung, D. Tank, R.H. Austin,
Nano Letters, 6 (2) Article featured in Analytical Chemistry 78(7), 2082 APR 2006. - More than 150 citations., (Feb 2006), 169-174
Restriction mapping in nanofluidic devices.
R. Riehn, M. Lu, Y.M. Wang, S. F. Lim, E.C. Cox, R.H. Austin,
PNAS 102, (29), (July 2005), 10012-10016