Rapid and accurate response to targeted therapies is critical to differentiate tumors that are resistant to treatment early in the regimen. In this work, we demonstrate a rapid, noninvasive, and label-free approach to evaluate treatment response to molecular inhibitors in breast cancer (BC) cells with Raman spectroscopy (RS). Metabolic reprograming in BC was probed with RS and multivariate analysis was applied to classify the cells into responsive or nonresponsive groups as a function of drug dosage, drug type, and cell type. Metabolites identified with RS were then validated with mass spectrometry. Our findings support that oncometabolites identified with RS will ultimately enable rapid drug screening in patients ensuring patients receive the most effective treatment at the earliest time point.
Precise monitoring of specific biomarkers in biological fluids with accurate biodiagnostic sensors is critical for early diagnosis of diseases and subsequent treatment planning. In this work, we demonstrated an innovative biodiagnostic sensor, PRADA: portable reusable accurate diagnostics with nanostar antennas, for multiplexed biomarker detection in small volumes enabled in a microfluidic platform. Here, PRADA simultaneously detected two biomarkers of myocardial infarction, cardiac troponin I, which is well accepted for cardiac disorders, and neuropeptide Y, which controls cardiac sympathetic drive. We envision low-cost PRADA will have tremendous translational impact and amenable to resource-limited settings for accurate treatment planning in patients.
The interactions of programmed death protein-1 (PD-1) on T cells with its ligand, PD-L1, strongly contributes to an immunosuppressive microenvironment. Blockades of PD-L1 have shown long-term survival in patients. However, <30% of patients respond to PD-L1 blockade, in part due to inaccurate identification of PD-L1 expression. An unmet clinical need exists for noninvasive detection techniques. Surface-enhanced Raman spectroscopy (SERS) imaging mediated by gold nanostructures has gained interest as a pre-clinical noninvasive diagnostic tool due to the high spatial resolution, portability, low cost, and rapid analysis. In this work, we demonstrate the use of gold nanostars conjugated with Raman tags for multiplexed SERS and simultaneous diagnosis of PD-L1 and epidermal growth factor receptor (EGFR) in vivo. Nanostars conjugated with anti-PDL1 antibodies/DTNB Raman molecule, and nanostars conjugated with anti-EGFR antibodies/pMBA Raman molecules were concurrently introduced to mice. Longitudinal Raman analysis demonstrated maximum accumulation of nanostars occurred 6h post IV delivery when strong increases in SERS signals for both Raman tags were observed. Raman signals decreased by 30% when both targeted receptors were pre-blocked with antibody (IP), indicating both the sensitivity and specificity of our platform in distinguishing tumors with varied expression of PD-L1 and EGFR. Furthermore, ex-vivo Raman maps provided assessment of biomarker status with cellular-resolution, and nanostars distribution in tumors. Finally, gold contents in organs were quantified with inductively coupled plasma mass spectrometry to evaluate their pharmacokinetics and biodistribution. This work shows gold nanostars-mediated SERS imaging provides a quantitative measure of PD-L1 to allow predictive and personalized immunotherapies with minimal toxicities.
KEYWORDS: Solar energy, Silicon, Solar cells, Photovoltaics, Dye sensitized solar cells, Solid state electronics, Electrodes, Etching, Interfaces, Silicon solar cells
This work will discuss our recent advances focused on integrating high power energy storage directly into the native materials of both conventional photovoltaics (PV) and dye-sensitized solar cells (DSSCs). In the first case (PV), we demonstrate the ability to etch high surface-area porous silicon charge storage interfaces directly into the backside of a conventional polycrystalline silicon photovoltaic device exhibiting over 14% efficiency. These high surface area materials are then coupled with solid-state ionic liquid-polymer electrolytes to produce solid-state fully integrated devices where the PV device can directly inject charge into an on-board supercapacitor that can be separately discharged under dark conditions with a Coulombic efficiency of 84%. In a similar manner, we further demonstrate that surface engineered silicon materials can be utilized to replace Pt counterelectrodes in conventional DSSC energy conversion devices. As the silicon counterelectrodes rely strictly on surface Faradaic chemical reactions with the electrolyte on one side of the wafer electrode, we demonstrate double-sided processing of electrodes that enables dual-function of the material for simultaneous energy storage and conversion, each on opposing sides. In both of these devices, we demonstrate the ability to produce an all-silicon coupled energy conversion and storage system through the common ability to convert unused silicon in solar cells into high power silicon-based supercapacitors. Beyond the proof-of-concept design and performance of this integrated solar-storage system, this talk will conclude with a brief discussion of the hurdles and challenges that we envision for this emerging area both from a fundamental and technological viewpoint.
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