Wadduwage Lab for Differentiable Microscopy (𝜕𝜇)

In Wadduwage Lab, we work on novel computational microscopy solutions that can measure biological systems at their most information rich form, with minimum redundancy.

twitter | @nawodyaw
email | wadduwage@fas.harvard.edu

𝜕𝜇 – Differentiable Microscopy | With applications ranging from, rare cellular event detection to drug screening, high content imaging provides biomedically important morphological features of cells or tissues via high speed acquisition hardware and fast image processing algorithms. Despite significant advances in faster and more multiplexed imaging sensors, the imaging throughput is currently limited by the speed of electronics hardware. In Wadduwage Lab we use an orthogonal approach, termed differential microscopy (𝜕𝜇), to improve the imaging throughput beyond existing electronic hardware bottleneck. The rationale for 𝜕𝜇 is that low-dimensional compressed representations of image signals exists and can be found through learning-based techniques; instruments can thus be designed to perform measurements on the lower dimensional compressed representation, improving the throughput by the factor of compression. To achieve this, 𝜕𝜇 models the front-end optics, the back-end image -reconstruction and -processing algorithms together as a differentiable model of learnable parameters.

Team

Alumni

David Andre Coucheron – Associate Professor, University of Tromso (Former Collaborative PhD student)
Ishan Baliyan – Undergraduate Student, University of Waterloo(Former High School Research Intern)
Liana Owen – Undergraduate Student, HU ‘22 (Former Undergraduate Researcher)
Navodini Wijethilake – Doctoral Student, King’s College London (Former Post Graduate Researcher)
Zhun Wei – Assistant Professor, Zhejiang University (Former Postdoctoral Fellow)

Publications

  • Pradeepkumar J., Anandakumar M., Kugathasan V., Seeber A., & Wadduwage, D.N.*, 2021. Physics Augmented U-Net: A High-Frequency Aware Generative Prior for Microscopy. bioRxiv 2021.12.01.470743.
  • Zheng, C., Park, J.K., Yildirim, M., Boivin, J.R., Xue, Y., Sur, M., So, P.T. & Wadduwage, D.N.*, 2021. De-scattering with Excitation Patterning enables rapid wide-field imaging through scattering media. Science Advances, 7(28), p.eaay5496.
  • Kay, J.E., Corrigan, J.J., Armijo, A.L., Nazari, I.S., Kohale, I.N., Torous, D.K., Avlasevich, S.L., Croy, R.G., Wadduwage, D.N., Carrasco, S.E. and Dertinger, S.D., 2021. Excision of mutagenic replication- blocking lesions suppresses cancer but promotes cytotoxicity and lethality in nitrosamine-exposed mice. Cell Reports, 34(11), p.108864.
  • Kay, J.E., Mirabal, S., Briley, W.E., Kimoto, T., Poutahidis, T., Ragan, T., So, P.T., Wadduwage, D.N., Erdman, S.E. and Engelward, B.P., 2021. Analysis of mutations in tumor and normal adjacent tissue via fluorescence detection. Environmental and Molecular Mutagenesis, 62(2), pp.108-123.
  • Agbleke, A.A., Amitai, A., Buenrostro, J.D., Chakrabarti, A., Chu, L., Hansen, A.S., Koenig, K.M., Labade, A.S., Liu, S., Nozaki, T. and Ovchinnikov, S., Seeber, A., Shaban, H. A., Spille, J., Stephens, A. D., Su, J., Wadduwage, D.N., 2020. Advances in chromatin and chromosome research: perspectives from multiple fields. Molecular Cell.
  • Wei, Z., Boivin, J.R., Xue, Y., Chen, X., So, P.T., Nedivi, E. & Wadduwage, D.N.*, 2019. 3D Deep Learning Enables Fast Imaging of Spines through Scattering Media by Temporal Focusing Microscopy. arXiv preprint arXiv:2001.00520.
  • Coucheron, D.A., Wadduwage, D.N., Murugan, G.S., So, P.T. & Ahluwalia, B.S.*, 2019. Chip-based resonance Raman spectroscopy using tantalum pentoxide waveguides. IEEE Photonics Technology Letters, 31(14), pp.1127-1130.
  • Xue, Y., Berry, K.P., Boivin, J.R., Wadduwage, D. N., Nedivi, E. & So, P.T.*, 2018. Scattering reduction by structured light illumination in line-scanning temporal focusing microscopy. Biomedical optics express, 9(11), p.5654.
  • Wadduwage, D.N.*, Kay, J., Singh, V.R., Kiraly, O., Sukup-Jackson, M.R., Rajapakse, J., Engelward, B.P. & So, P.T., 2018. Automated fluorescence intensity and gradient analysis enables detection of rare fluorescent mutant cells deep within the tissue of RaDR mice. Scientific reports, 8(1), p.12108.
  • Wadduwage, D.N., Singh, V.R., Choi, H., Yaqoob, Z., Heemskerk, H., Matsudaira, P. and So, P.T.*, 2017. Near-common-path interferometer for imaging Fourier-transform spectroscopy in wide-field microscopy. Optica, 4(5), pp.546-556.
  • Wadduwage, D.N., Parrish, M., Choi, H., Engelward, B.P., Matsudaira, P. and So, P.T.*, 2015, June. Subnuclear foci quantification using high-throughput 3D image cytometry. In European Conference on Biomedical Optics (p. 953607). Optical Society of America.
  • Choi, H., Wadduwage, D.N., Tu, T.Y., Matsudaira, P. and So, P.T.*, 2015. Threeâdimensional image cy- tometer based on widefield structured light microscopy and highâspeed remote depth scanning. Cytometry Part A, 87(1), pp.49-60.
  • Choi, H., Wadduwage, D.N., Matsudaira, P.T. and So, P.T.*, 2014. Depth resolved hyperspectral imag- ing spectrometer based on structured light illumination and Fourier transform interferometry. Biomedical optics express, 5(10), pp.3494-3507.
  • Sukup-Jackson, M.R., Kiraly, O., Kay, J.E., Na, L., Rowland, E.A., Winther, K.E., Chow, D.N., Kimoto, T., Matsuguchi, T., Jonnalagadda, V.S., Maklakova, V.I., Singh V.R., Wadduwage D.N., Rajapakse J., So P.T., Collier L.S., & Engelward* B.P., 2014. Rosa26-GFP direct repeat (RaDR-GFP) mice reveal tissue- and age-dependence of homologous recombination in mammals in vivo. PLoS genetics, 10(6), p.e1004299.