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Quantum cascade lasers (QCLs) have broken the spectral barriers of semiconductor lasers and enabled a range of applications in the mid-infrared (MIR) and terahertz (THz) regimes. However, until recently, generating ultrashort and intense pulses from QCLs has been difficult. This would be useful to study ultrafast processes in MIR and THz using the targeted wavelength-by-design properties of QCLs. Since the first demonstration in 2009, mode-locking of QCLs has undergone considerable development in the past decade, which includes revealing the underlying mechanism of pulse formation, the development of an ultrafast THz detection technique, and the invention of novel pulse compression technology, etc. Here, we review the history and recent progress of ultrafast pulse generation from QCLs in both the THz and MIR regimes. 

A terahertz (THz) frequency comb capable of high-resolution measurement will significantly advance THz technology application in spectroscopy, metrology and sensing. The recently developed cryogenic-cooled THz quantum cascade laser (QCL) comb has exhibited great potentials with high power and broadband spectrum. Here, we report a room temperature THz harmonic frequency comb in 2.2 to 3.3 THz based on difference-frequency generation from a mid-IR QCL. The THz comb is intracavity generated via down-converting a mid-IR comb with an integrated mid-IR single mode based on distributed-feedback grating without using external optical elements. The grating Bragg wavelength is largely detuned from the gain peak to suppress the grating dispersion and support the comb operation in the high gain spectral range. Multiheterodyne spectroscopy with multiple equally spaced lines by beating it with a reference Fabry-Pérot comb confirms the THz comb operation. This type of THz comb will find applications to room temperature chip-based THz spectroscopy.

 

The inception and development of supramolecular chemistry have provided a vast library of supramolecular structures and materials for improved practice of medicine. In the context of therapeutic delivery, while supramolecular nanostructures offer a wide variety of morphologies as drug carriers for optimized targeting and controlled release, concerns are often raised as to how their morphological stability and structural integrity impact their in vivo performance. After intravenous (i.v.) administration, the intrinsic reversible and dynamic feature of supramolecular assemblies may lead them to dissociate upon plasma dilution to a concentration below their critical micellization concentration (CMC). As such, CMC represents an important characteristic for supramolecular biomaterials design, but its pharmaceutical role remains elusive. Here, we report the design of a series of self-assembling prodrugs (SAPDs) that spontaneously associate in aqueous solution into supramolecular polymers (SPs) with varying CMCs. Two hydrophobic camptothecin (CPT) molecules were conjugated onto oligoethylene-glycol (OEG)-decorated segments with various OEG repeat numbers (2, 4, 6, 8). Our studies show that the lower the CMC, the lower the maximum tolerated dose (MTD) in rodents. When administrated at the same dosage of 10 mg/kg (CPT equivalent), SAPD 1, the one with the lowest CMC, shows the best efficacy in tumor suppression. These observations can be explained by the circulation and dissociation of SAPD SPs and the difference in molecular and supramolecular distribution between excretion and organ uptake. We believe these findings offer important insight into the role of supramolecular stability in determining their therapeutic index and in vivo efficacy.

 

Self‐assembly of peptide‐based building units into supramolecular nanostructures creates an important class of biomaterials with robust mechanical properties and improved resistance to premature degradation. Yet, upon aggregation, substrate–enzyme interactions are often compromised because of the limited access of macromolecular proteins to the peptide substrate, leading to either a reduction or loss of responsiveness to biomolecular cues. Reported here is the supramolecular design of unsymmetric reverse bolaamphiphiles (RBA) capable of exposing a matrix metalloproteinase (MMP) substrate on the surface of their filamentous assemblies. Upon addition of MMP‐2, these filaments rapidly break into fragments prior to reassembling into spherical micelles. Using 3D cell culture, it is shown that drug release is commensurate with cell density, revealing more effective cell killing when more cancer cells are present. This design platform could serve as a cell‐responsive therapeutic depot for local chemotherapy.

 

Self‐assembly of peptide‐based building units into supramolecular nanostructures creates an important class of biomaterials with robust mechanical properties and improved resistance to premature degradation. Yet, upon aggregation, substrate–enzyme interactions are often compromised because of the limited access of macromolecular proteins to the peptide substrate, leading to either a reduction or loss of responsiveness to biomolecular cues. Reported here is the supramolecular design of unsymmetric reverse bolaamphiphiles (RBA) capable of exposing a matrix metalloproteinase (MMP) substrate on the surface of their filamentous assemblies. Upon addition of MMP‐2, these filaments rapidly break into fragments prior to reassembling into spherical micelles. Using 3D cell culture, it is shown that drug release is commensurate with cell density, revealing more effective cell killing when more cancer cells are present. This design platform could serve as a cell‐responsive therapeutic depot for local chemotherapy.