Howard Hughes Medical Institute

Harvard College

Element Biosciences, Inc.

Tsung-Li Liu

Kai Wang

Wesley Legant

Daniel E Milkie

Chunhong Zhou

Eric Betzig

Sinan Arslan

Junhua Zhao

Evelyn Lynn Hu

William Light

Hua Yu

Michael Kim

Kasey Joe Russell

Ramreddy Tippana

Robert Eric Betzig

The present disclosure provides compositions and related methods, e.g., for preparing immobilized nucleic acid nanostructures using compaction oligonucleotides. In some embodiments, rolling circle amplification reaction can be conducted with compaction oligonucleotides on-support or in-solution to generate concatemer molecules having multiple copies of a polynucleotide unit arranged in tandem. Each polynucleotide unit comprises a sequence-of-interest and at least one universal adaptor sequence that binds one end of a compaction oligonucleotide. The 5' and 3′ regions of the compaction oligonucleotide can hybridize to the concatemer to pull together distal portions of the concatemer causing compaction of the concatemer to form a nanostructure. Nanostructures having tighter size and shape compared to concatemers generated in the absence of the compaction oligonucleotides. The compact and stable characteristics of the nucleic acid nanostructures improves sequencing accuracy by increasing signal intensity and they retain their shape and size during multiple sequencing cycles.

Compositions and methods for preparing nucleic acid nanostructures using compaction oligonucleotides

A microscope directs light through an excitation objective to generate a lattice light sheet (LLS) within a sample. A detection objective collects signal light from the sample in response to the LLS and images the collected light onto a detector. Second and third light beams are imaged onto focal planes of the excitation objective and detection objective, respectively. One or more wavefront detectors determine wavefronts of light emitted from the sample and through the excitation objective in response to the imaged second light beam and emitted from the sample through the detection objective in response to the imaged third light beam. A wavefront of the first light beam is modified to reduce a sample-induced aberration of the LLS within the sample, and a wavefront of the signal light emitted from the sample is modified to reduce a sample-induced aberration of the signal light at the detector.

High-resolution, real-time imaging with adaptive optics and lattice light sheets

A light emitting device is described that may reduce the coupling of emitted light into silicon and may increase the efficiency with which light is emitted into the far field. Such a device may include a semiconductor layer, a metallic structure, and a light emission layer disposed between the semiconductor layer and the metallic structure. The light emission layer may be in physical contact with the metallic structure and the semiconductor layer. The light emission layer may include at least one fluorescent molecule that emits light upon excitation.

Metal-based optical device enabling efficient light generation from emitters on a high-index absorbing substrate

Growing community of inventors

San Diego, CA, United States of America

Tsung-Li Liu