Guided wave resonance-based digital holographic microscopy for high-sensitivity monitoring of the refractive index.

Surface plasmon resonance holographic microscopy (SPRHM) has been employed to measure the refractive index but whose performance is generally limited by the metallic intrinsic loss. Herein we first, to our knowledge, utilize guided wave resonance (GWR) with low loss to realize the monitoring of the refractive index by integrating with digital holographic microscopy (DHM). By depositing a dielectric layer on a silver film, we observe a typical GWR in the dielectric layer with stronger field enhancement and higher sensitivity to the surrounding refractive index compared to the silver film-supported SPR, which agrees well with calculations. The innovative combination of the GWR and DHM contributes to the highly sensitive dynamic monitoring of the surrounding refractive index variation. Through the measurement with DHM, we found that the GWR presents an excellent sensitivity, which is 2.6 times higher than that of the SPR on the silver film. The results will pave a new pathway for digital holographic interferometry and its applications in environmental and biological detections.

Thickness measurement of bimetallic film using surface plasmon resonance holographic microscopy.

Bimetallic film with high stability and sensitivity is often used to excite surface plasmon resonance (SPR). The thicknesses of the bimetallic film play an important role in quantitative retrieval of the sample's parameters, and a precise measurement method is not available until now. In this paper, we propose a method for measuring the thicknesses of bimetallic film using surface plasmon resonance holographic microscopy (SPRHM). Considering that the refractive index of the dielectric upon the bimetallic film sensitively modulates the SPR phase response, the two thickness parameters of bimetallic film can be calculated by two phase-contrast SPR images with two different liquid dielectrics. The capability of this method was verified with several Ag-Au film couples by using a compact SPRHM setup. Our work provides a precise characterization method for the parameters of SPR configuration and may find wide applications in the research fields of SPR sensing and imaging.

Label-free and dynamic monitoring of cell evolutions using wavelength-multiplexing surface plasmon resonance holographic microscopy.

Dynamic characterizations of intracellular variations and cell-substrate interactions under different external environments are critical to study cell behaviors and exploring biological applications. However, techniques that are capable of dynamically and simultaneously measuring multiple parameters of living cells in a wide-field manner have rarely been reported. Here, we present a wavelength-multiplexing surface plasmon resonance holographic microscopy which allows wide-field, simultaneous, and dynamic measurements of cell parameters, including cell-substrate distance and cytoplasm refractive index (RI). We use two lasers of 632.8 nm and 690 nm as light sources. Two beam splitters are employed in the optical setup to separately adjust the incident angle of two light beams. Then, surface plasmon resonance (SPR) can be excited for each wavelength under SPR angles. We demonstrate the advances of the proposed apparatus by systematically studying the cell responses to osmotic pressure stimuli from the environmental medium at the cell-substrate interface. The SPR phase distributions of the cell are firstly mapped at two wavelengths, then the cell-substrate distance and cytoplasm RI are retrieved using a demodulation method. Based on phase response differences between two wavelengths and monotonic changes of SPR phase with cell parameters, cell-substrate distance, and cytoplasm RI can be determined simultaneously using an inverse algorithm. This work affords a new optical measurement technique to dynamically characterize cell evolutions and investigate cell properties in various cellular activities. It may become a useful tool in the bio-medical and bio-monitoring areas.

Synthesis and evaluation of hydrazinyl-containing pyrrolo[2,3-d]pyrimidine series as potent, selective and oral JAK1 inhibitors for the treatment of rheumatoid arthritis.

Selective inhibition of JAK kinases within the JAK family has been a desired goal of research in order to maximize efficacy while reducing undesired off target effect. Aiming to minimize adverse effects such as anemia, a promising new class of pyrrolo[2,3-d]pyrimidine series containing a hydrazinyl moiety were synthesized and profiled. Among them compound 8m and 8o showed the best enzymatic activity against JAK1 with IC50 value of 0.16 nM and 0.3 nM respectively, and with selectivity over JAK2 by 40.6 and 10 folds respectively. In addition, 8o had an improved PK profile and demonstrated better in vivo efficacy than Tofacitinib in CIA model.

Dual-wavelength surface plasmon resonance holographic microscopy for simultaneous measurements of cell-substrate distance and cytoplasm refractive index.

Studying the basic characteristics of living cells is of great significance in biological research. Bio-physical parameters, including cell-substrate distance and cytoplasm refractive index (RI), can be used to reveal cellular properties. In this Letter, we propose a dual-wavelength surface plasmon resonance holographic microscopy (SPRHM) to simultaneously measure the cell-substrate distance and cytoplasm RI of live cells in a wide-field and non-intrusive manner. Phase-contrast surface plasmon resonance (SPR) images of individual cells at wavelengths of 632.8 nm and 690 nm are obtained using an optical system. The two-dimensional distributions of cell-substrate distance and cytoplasm RI are then demodulated from the phase-contrast SPR images of the cells. MDA-MB-231 cells and IDG-SW3 cells are experimentally measured to verify the feasibility of this approach. Our method provides a useful tool in biological fields for dual-parameter detection and characterization of live cells.

Optical tweezers integrated surface plasmon resonance holographic microscopy for characterizing cell-substrate interactions under noninvasive optical force stimuli.

The rapid development of bio-mechanical research increases the significance of studying cell behaviors near the substrate under the force stimuli in a real-time manner. Here, we present an optical tweezers (OT) integrated surface plasmon resonance holographic microscopy (SPRHM) to realize the dynamical and in-situ characterizations of cell-substrate interactions with noninvasive optical force stimulations. Using the OT integrated SPRHM (OT-SPRHM), we dynamically manipulate the living cells by OT, and simultaneously, the phase-contrast surface plasmon resonance images of the living cells are obtained and the cell-substrate distance is determined via SPRHM. We show that OT-SPRHM has the advanced capabilities of measuring the optical force and its tiny variations applied to the K562 cells near the substrate. Also, we for the first time reveal the manipulation of the MC3T3-E1 cells by OT. Demonstrating its robustness, this technique provides a powerful tool to explore the responses of various biological specimens to the force stimuli along the cell-substrate interface in the bio-sensing area.