Herein we describe a new class of microfluidic immunoassays based upon solid supported lipid bilayers. Two-dimensionally fluid bilayer material, which can accommodate multivalent binding between surface-bound ligands and aqueous receptors, was coated on the surface of poly(dimethylsiloxane) microchannels. The bilayers contained dinitrophenyl (DNP)-conjugated lipids for binding with bivalent anti-DNP antibodies. Twelve independent data points of surface coverage versus bulk protein concentration could be made simultaneously by forming a linear array of channels and flowing fluorescently labeled antibodies into them. This enabled an entire binding curve to be obtained in a single experiment. The measured apparent binding constant for the DNP/anti-DNP system was 1.8 microM. The methodology for performing heterogeneous assays developed here not only produces rapid results but also requires much less protein than traditional procedures and eliminates some standard sources of experimental error.
spatial profi le. Gradient metasurfaces provide a much richer control of the wavefront in both local amplitude and phase of the emerging transmitted and refl ected beams. [4][5][6][7] Such structures enable fl at optical components for beam focusing, polarization control and phase correction, to name a few examples. [4][5][6][7][8][9] The next challenge and exciting perspective for this technology consists in enabling real-time reconfi gurability of the metasurface platform with a fast response time, which may produce fl at optical components for rapid wavefront modulation, phase tuning and beam steering. [ 7 ] A number of methods to tune the spectral response of plasmonic nanoresonators have been reported in the recent past, based on thermal, mechanical, optical, and electrical control, as summarized in the literature. [ 10 ] Electrical tuning techniques are of particular interest, since they open a route to on-chip integration of metasurfaces with electronics, potentially enabling GHz-level switching speeds. The most common electrical tuning mechanisms reported so far are based on phasechange media, [11][12][13] the use of liquid crystals, [ 14,15 ] and carrier concentration control on a semiconductor substrate [ 16,17 ] or graphene. [18][19][20][21][22][23] Approaches based on phase-change media and liquid crystals rely on intrinsically slow physical processes and cannot produce metasurfaces with nanosecond switching time. Carrier-concentration control produces metasurfaces with much faster switching speeds with the best results in terms of tuning range and switching speeds achieved with hybrid metal−graphene structures, demonstrating spectral tuning with switching speeds up to 30 MHz, [ 23 ] limited by the RC (circuit resistance × circuit capacitance) time constant of the biasing circuit.It has recently been suggested and experimentally demonstrated by our team [ 24,25 ] as well as by Brener's group in Sandia Labs [26][27][28] that metasurfaces made of plasmonic nanoresonators polaritonically coupled [29][30][31][32] to intersubband transitions in multi-quantum-well (MQW) semiconductor heterostructures engineered for large quantum confi ned Stark effect [33][34][35] may display voltage-tunable optical response. Here we demonstrate that these polaritonic metasurfaces may provide one of the fastest electrical switching of optical response demonstrated in metasurfaces to date. Our structures utilize well-established InGaAs/AlInAs MQW semiconductor technology and demonstrate comparable absorption modulation speed compared to hybrid metal−graphene structures while using lower bias Electrically tunable mid-infrared metasurfaces with nanosecond response time and broad tuning range are reported. Electrical tuning is achieved by employing strong polaritonic coupling of electromagnetic modes in metallic nanoresonators with voltage-tunable inter-subband transitions in semiconductor heterostructures, tailored for a giant quantum-confi ned Stark effect. Experimentally, a 220-nm-thick multi-quantum-well semiconductor layer...
We discuss the design and operation of widely-tunable terahertz sources based on Cherenkov intra-cavity difference-frequency generation in mid-infrared quantum cascade lasers. Laser chips are integrated into a Littrow-type external cavity system. Devices demonstrate continuous terahertz emission tuning at room temperature with a record tuning range from 1.2 THz to 5.9 THz and peak power output varying between 5 and 90 μW, depending on the operating frequency. Beam steering of terahertz Cherenkov emission with frequency is suppressed and mid-infrared-to-terahertz conversion efficiency is improved by bonding devices onto highresistivity silicon substrates that have virtually no refractive index dispersion and vanishinglysmall optical loss in 1-6 THz range.
Cell-free systems offer a simplified and flexible context that enables important biological reactions while removing complicating factors such as fitness, division, and mutation that are associated with living cells. However, cell-free expression in unconfined spaces is missing important elements of expression in living cells. In particular, the small volume of living cells can give rise to significant stochastic effects, which are negligible in bulk cell-free reactions. Here, we confine cell-free gene expression reactions to cell-relevant 20 fL volumes (between the volumes of Escherichia coli and Saccharomyces cerevisiae ), in polydimethylsiloxane (PDMS) containers. We demonstrate that expression efficiency varies widely among different containers, likely due to non-Poisson distribution of expression machinery at the observed scale. Previously, this phenomenon has been observed only in liposomes. In addition, we analyze gene expression noise. This analysis is facilitated by our use of cell-free systems, which allow the mapping of the measured noise properties to intrinsic noise models. In contrast, previous live cell noise analysis efforts have been complicated by multiple noise sources. Noise analysis reveals signatures of translational bursting, while noise dynamics suggest that overall cell-free expression is limited by a diminishing translation rate. In addition to offering a unique approach to understanding noise in gene circuits, our work contributes to a deeper understanding of the biophysical properties of cell-free expression systems, thus aiding efforts to harness cell-free systems for synthetic biology applications.
Electrically pumped room-temperature semiconductor sources of tunable terahertz radiation in 1-5 THz spectral range are highly desired to enable compact instrumentation for THz sensing and spectroscopy. Quantum cascade lasers with intra-cavity difference-frequency generation are currently the only room-temperature electrically pumped semiconductor sources that can operate in the entire 1-5 THz spectral range. Here we demonstrate that this technology is suitable to implementing monolithic room-temperature terahertz tuners with broadband electrical control of the emission frequency. Experimentally, we demonstrate ridge waveguide devices electrically tunable between 3.44 and 4.02 THz.
Terahertz quantum cascade laser (QCL) sources based on intra-cavity difference frequency generation are currently the only electrically pumped monolithic semiconductor light sources operating at room temperature in the 1–6-THz spectral range. Relying on the active regions with the giant second-order nonlinear susceptibility and the Cherenkov phase-matching scheme, these devices demonstrated drastic improvements in performance in the past several years and can now produce narrow-linewidth single-mode terahertz emission that is tunable from 1 to 6 THz with power output sufficient for imaging and spectroscopic applications. This paper reviews the progress of this technology. Recent efforts in wave function engineering using a new active region design based on a dual-upper-state concept led to a significant enhancement of the optical nonlinearity of the active region for efficient terahertz generation. The transfer of Cherenkov devices from their native semi-insulating InP substrates to high-resistivity silicon substrates resulted in a dramatic improvement in the outcoupling efficiency of terahertz radiation. Cherenkov terahertz QCL sources based on the dual-upper-state design have also been shown to exhibit ultra-broadband comb-like terahertz emission spectra with more than one octave of terahertz frequency span. The broadband terahertz QCL sources operating in continuous-wave mode produces the narrow inter-mode beat-note linewidth of 287 Hz, which indicates frequency comb operation of mid-infrared pumps and thus supports potential terahertz comb operation. Finally, we report the high-quality terahertz imaging obtained by a THz imaging system using terahertz QCL sources based on intra-cavity difference frequency generation.
Supporting InformationPhotolithography PDMS molds were fabricated with multilayer photolithographic techniques. Briefly, negative tone photomasks for the control and mixer layers were printed on transparency films at 20,000 dots per inch resolution by CAD/Art Services (Bandon, OR). A chrome mask with arrays of 5 μm dots was purchased from MEMS and Nanotechnology Exchange (Reston, VA). To make the mold for the mixer/chamber layer, SU8 2005 was first spun at 2000 rpm on a piece of isopropanol-cleaned silicon. After soft baking(1 min at 65°C and 2 min at 95°C), the 5 μm dot arrays as well as alignment marks were transferred from the chrome mask to the resist by UV exposure at 4.5 mW/cm 2 for 90 sec, followed by postexposure baking (1 min at 65°C and 1 min at 95°C), and development in SU8 developer. 5 μm dot patterns were further stabilized by hard baking at 150°C for 5 min. Another layer of 25 μm thick SU8 2025 photoresist was then spin-coated on top of the dot pattern and soft baked (1 min at 65°C and 3 min at 95°C). Each 5 μm chamber had a volume of approximately 100 femtoliters (4.4 μm diameter with 6.5 μm height), as inferred from scanning electron microscopy (SEM) images of the microchambers.To align the staggered herringbone mixer patterns relative to the array of dots, four corners of the silicon chip were carefully cleared with SU8 developer to reveal the alignment marks on the mold. The mixer patterns were then transferred to the second resist layer through the transparency mask by UV
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