Precision medicine refers to giving the right therapeutics, to the right patient, at the right time. In the context of cancer, successful implementation of precision medicine, requires treatment individualization not only taking into account patient and tumor factors, but also tumor heterogeneity and tumor evolution over time. In this study, a continuous flow microfluidic device was developed as a functional flow cytometer (m-FACS) to detect secreted multiplexed protease activities at single cell resolution. The individual cells from patient samples are encapsulated within water-in-oil droplets for single cell multiplexed protease assay. We modified FRET (fluorescence resonance energy transfer)-based substrates to accommodate different fluorescent pairs with distinct excitation and emission wavelengths to obtain multiple signals from droplets containing single cells. Four substrate-protease reactions in a droplet were simultaneously monitored at three distinct pairs of fluorescent excitation (UV: 400nm, B: 470nm, G: 546nm, R: 635nm) and emission (B: 520nm, G: 580nm, R: 670nm) wavelengths. To infer a quantitative profile of multiple proteolytic activities from single cells, we applied the computational method Proteolytic Activity Matrix Analysis (PrAMA). The capability to determine multiple protease activities at single cell resolution has the potential to characterize tumor progress of individual patients.

Stable micro-emulsion droplets as miniaturized reactors have enabled a wide range of synthetic and bioanalytical applications, and still promise to give rise to many innovations to come. Partitioning plays an essential part in digital bioanalytical assays, which requires uniformity, stability and high throughput. Dividing reaction mix into hundreds or thousands of microcentrifuge tubes/vials was first employed in the early stages of digital PCR[1] which being costly and laborious was soon replaced. Later came nanoliter to femtoliter reaction chambers in polymer or glass made microfluidic devices, [2-4] or water-in-oil (w/o) emulsion droplets. [5, 6] Currently the emulsion based approaches have become the most popular method used in research and medical laboratories. However, the cost of microfluidic chip-based emulsion generating devices, as well as their control instruments, are still relatively high. Not only are the in-house designed microfluidic devices too complex to be adapted by other labs, but also many commercially available instruments require extra skills to process properly.

Using bench-top centrifuge, we develop a novel method of producing monodisperse emulsion droplets by micro-channel array (MiCA). Subjected to the centrifuge, aqueous liquid ejects out at the nozzles of the micro-channel into monodispersed droplets, which then are stabilized by the receiving oil underneath. Within few minutes, >3x10⁵ pico-liter droplets can be generated without complicated handling of microfluidics devices and control system. By tuning the spinning speed and changing the MiCA with different channel number or sizes, we are able to generate droplets of various size.  We demonstrate digital PCR and LAMP assays through MiCA approach. The digital PCR result is highly concordant with commercial equipment (Bio-Rad QX200). Our newly formulated digital LAMP protocol has also see favorable linearity in dilution quantification experiments.

MiCA-enabled emulsion generation is facile and robust, exhibiting great advantage over conventional lab equipment. With the cost-effective and highly precise micro-channel array (MiCA) the aqueous solution can be dispersed into stable picoliter-droplets and then perform PCR thermal cycling without extra liquid transfer in microcentrifuge tubes, significantly reducing the difficulty and complexity of performing droplet-based biological and chemical assays, and minimizing the loss of rare input materials by eliminating the dead volume. By the virtue of centrifuge this novel emulsion generation method is intrinsically highly parallel given that many samples can be processed simultaneously without contamination.

Metasurfaces are ultra-thin planar structures designed with extraordinary electromagnetic properties from the interaction between the subwavelength scatterers and the electromagnetic radiation. Nevertheless, the dispersion nature imbedded in the metallic resonator of the metasurfaces leads to the variation of the angle of reflection. The reflection angle changes with the incident frequency of the electromagnetic waves. Here, we demonstrate, for the first time, an active metasurface with dynamically controllable dispersion by individually reconfiguring the geometry (shape and orientation) of the resonators. The latter are liquid metal rings structured and controlled by a microfluidic system. By tailoring the phase profile of the scattered light, we present a dispersion-controllable beam steering function whereby the steering angle is kept at -45˚ for three normal incident frequencies of 10.5, 12 and 14 GHz. Such active metasurfaces have potential applications in 2 directional communication devices, multi-frequency tracking Radar systems, and broadband scanning system.

Metasurfaces based on sub-wavelength patterning have major potential for arbitrary control of the wavefront of light by achieving local control of the phase, amplitude and polarization and allowing greater functionality and more compact devices. High performance metasurfaces for the visible will be discussed including high NA metalenses for subwavelength imaging, achromatic lenses, axicons, vortex plates, chiral holograms, spin-to-orbital angular momentum converters, ultracompact spectrometers and novel waveplates will be discussed, along with the potential of this technology for a wide range of applications. 

Metasurfaces are ultra-thin artificial films built up using periodically arrayed sub-wavelength structures, which interact with electromagnetic wave performing extraordinary properties. Metasurfaces, as a new platform for flat optics, enable plenty of applications such as beam steering, flat lens, cloaking, polarization converter and waveplates and so forth.  However, metasurfaces’ power of tailoring the properties of electromagnetic waves is suppressed by the fixed structure of metasurfaces. Metasurfaces with tunable functions or multi-functions are desirable for practical applications. Here, we present an active metasurface with high tuning power for multi-functions including dispersion-controlled focusing and beam tracking. In the metasurface, each miniaturized scatter is formed by injecting liquid metal into optofluidic ring-shaped channels. The geometry of the liquid metal is controlled using a pneumatic control system. This tunable metasurface achieved through microfluidic technology releases the great potential of metasurfaces for multi-functional devices, which paves the way for promising practical applications such as achromatic flat lens, beam scanning and beam tracking.

Aluminum-based localized surface plasmon resonance (LSPR) holds attractive properties including low cost, high natural abundance, and ease of processing by a wide variety of methods including complementary metal oxide semiconductor process, making it superior to conventional LSPR involving noble metals. It has great potential to be developed into large-scale arrays composed of highly miniaturized and uniform signal transducer elements, thereby widely used in the terminals of mobile healthcare, public health security and environmental monitoring.

In this presentation, we present an overview of our recent work on using aluminum nanostructured materials with LSPR for biosensing. Firstly, we introduce an aluminum nanopyramid array (NPA) with tunable ultraviolet-visible-infrared wavelength plasmon resonances. The Al NPA holds high RI sensitivity which is even comparable with that of noble metal, and can be used as a biosensor for rapid detection of carbohydrate antigen 199 (a biomarker specific to cancer exists in the digest system), with limit of detection determined to be 29 ng/mL. Secondly, we present a low-cost replication technique is introduced for the mass production of NPA. The method we developed has great potential in industrial production. Last, we apply the plasmonic nanostructures to real-time monitor the concentration change of hydrogen ion in saliva, and to rapidly determine the blood type and concentrations of red blood cells in human blood.

In this talk, we report our recent studies on anti-crossings and strong couplings between triple Fano resonances in a 3D metamaterial (MM). The 3D MMs are formed by integrating vertical asymmetric split-ring-resonators (aSRRs) along a planar metallic hole array with extraordinary optical transmission (EOT) built by means of homemade focused-ion-beam (FIB) folding technique. In such a configuration, the plasmonic system stably supports triple Fano resonance states. More importantly, the induced Fano resonances are widely tunable and strong couplings among triple Fano resonances occurs during the tuning process, which are well verified in both simulations and experiments. These 3D MMs with significant and robust Fano resonances exhibit an extremely high sensitivity to refractive index of the environments in the near infrared wavelength region.

In recent years, enhanced light-matter interactions through a plethora of dipole-type polaritonic excitations have been observed in two-dimensional (2D) layered materials. In graphene, electrically tunable and highly confined plasmon-polaritons were predicted and observed, opening up opportunities for optoelectronics, bio-sensing and other mid-infrared
applications. In this invited talk I will report our recent efforts on controlling light absorption and emission process through quantum effects.

For example, surface plasmons of different chirality can be excited in two dimensional materials that support transverse currents. We propose a method to optically excite and characterize the electromagnetic response and surface electromagnetic modes in a generic gapped Dirac material under pumping with circularly polarized light. The valley imbalance due to pumping leads to a net Berry curvature, giving rise to a finite transverse conductivity. Furthermore, we show that the historically studied two-dimensional (2D) magnetoplasmon, which bears gapped bulk states and gapless one-way edge states near-zero frequency, is topologically analogous to the 2D topological p+ip superconductor with chiral Majorana edge states and zero modes.  We also demonstrate experimentally ultrafast quenching of 2D molecular aggregates at picosecond timescale assisted by surface plasmons. Our analysis reveals that the metal-mediated dipole-dipole interaction increases the energy dissipation rate by at least five times faster than that predicted by conventional models. Our results can offer novel design pathways to the light-matter interaction in a variety of photon-exciton systems with applications such as high speed visible light communication.

DNA sequencing plays a significant role in modern human health diagnosis. It enables studies of metagenomics, genetic disorders, diseases, and genomic medicine.  For optical sequencing, a laser source, an optical filter and a Charge-Coupled Device (CCD)-based image sensor are employed. DNA sequence information is converted to light intensity through the use of fluorescence dyes. However, the involved optical imaging system is bulky and expensive that only hospitals and research centers can afford. In this paper, a miniaturized CMOS-image-sensor (CIS) based fluorescence detector is proposed to deal with these challenges. Firstly, semiconductor quantum dots (QDs) are employed. Compared to traditional organic fluorescence labels, QDs present higher quantum yields and longer life times. In this way, light intensity is enhanced from the source. Secondly, an on-chip optical filter is designed to reject the background excitation light and pass through the emission fluorescent light. Simulation results show that the 400~450nm excitation light is almost 100% absorbed and the 750~850nm fluorescent light is highly transparent. The transmission signal-to-noise ratio (SNR) between 400nm and 800nm can reach 64dB. Lastly, a 1-pA resolution Capacitive Transimpedance Amplifier (CTIA) with Correlated Double Sampling (CDS) are employed to realize a high-sensitivity readout circuit. Therefore, a highly CMOS integrated fluorescence imaging system can effectively reduce the size and cost of sequencing, which is a promising technique for personalized sequencing.

Spectropolarimeter is an optical instrument for characterizing the polarization state of light. Identifying the polarization state of light is an important diagnostic method in versatile applications. In this talk, a broadband plasmonic metasurface with Pancharatnam-Berry phase distribution is proposed to measure the polarization state of light through a birefringent material, which is a plastic tape. The birefringent tape with different numbers of layers represents different colors and is with varying phase delay for polarization eigen states. It is shown that the polarization state of light through birefringent tape measured by plasmonic metasurface has a fair agreement with that measured by a commercial polarimeter. This result shows that the metasurface has a potential as a compact spectropolarimeter.