Our lab engineers nanoscale imaging agents with precisely controlled physical structure and optical properties. We primarily focus on quantum dots (QDs), which are semiconductor nanoparticles that emit fluorescent light. Throughout the biomedical sciences, proteins and nucleic acids are chemically fused to fluorescent molecules for use as a light-emitting tag that can be measured in a cell or tissue. A key feature of QDs is their resistance to degradation; their stability is unmatched by any other type of fluorescent probe that can be integrated into biology, which has made them indispensable for imaging under conditions that would rapidly degrade normal organic dyes and fluorescent proteins. QDs are also unique because virtually any photophysical property can be tuned and controlled using engineering principles derived from semiconductor physics. Our lab discovers structure-function relationships to control photophysical properties of QDs and engineers the physical structure to control how they interface with cells and tissues.
Quantum dot photophysics
Our lab is advancing the fundamental science of, and ability to control, QD photophysics (how they absorb and emit light). One recent achievement is Brightness-Equalized Quantum Dots (BE-QDs), which overcame the problem that emission color and brightness were interdependent (Nat. Comm., 6: 8210, 2015). Color was previously tuned by QD size, which simultaneously dictates light absorption rate, and thus brightness. For BE-QDs, these parameters are decoupled because they derive from separate structural domains. We can now independently control color, absorption rate, and emission efficiency. There is no other material that provides this capability, allowing the design of QDs with different colors but equal brightness to allow new types of quantitative imaging. We continue to develop strategies for brightness engineering (Proc. SPIE, 933810, 2015) and study how spectra derive from physical structure (Nat. Comm., 8:14849, 2017), how electronic charge carriers are localized (Nat. Comm., 5: 4506, 2014), and how Raman spectra serve as footprints for internal spatial arrangements of atoms (J. Am. Chem. Soc., 138: 10887, 2016).
Quantum dot structure
QDs are composite particles composed of crystalline semiconductor materials as well as flexible organic coatings. While the crystalline core dictates the optical properties, the coating is the point of contact with the surrounding medium and determines how the material interacts with biology. A critical problem is that QDs are often big (30 nanometers) compared to protein constituents of biology (5-10 nanometers), so they become trapped in cells and tissues, unable to access molecular targets. We are developing new classes of thin organic coatings composed of multidentate polymers to address this problem (J. Am. Chem. Soc., 138: 3382, 2016). These multi-functional polymers simultaneously adsorb to QDs, resist cell binding, and provide click-chemistry attachment to targets, yielding the smallest stable QDs to date (7.4 nanometers) suitable for biological applications, with year-long shelf-life. We continue to tune structural components to further shrink size and to understand how physical and optical properties intertwine. Some of our engineering strategies were recently reviewed (Coord. Chem. Rev., 320-321: 216, 2016 and Curr. Opin. Chem. Eng., 4: 137, 2014).