A Multiplex "Disposable Photonics" Biosensor Platform and Its Application to Antibody Profiling in Upper Respiratory Disease.

Photonic technologies promise to deliver quantitative, multiplex, and inexpensive medical diagnostic platforms by leveraging the highly scalable processes developed for the fabrication of semiconductor microchips. However, in practice, the affordability of these platforms is limited by complex and expensive sample handling and optical alignment. We previously reported the development of a disposable photonic assay that incorporates inexpensive plastic micropillar microfluidic cards for sample delivery.

Acoustophoresis of a resonant elastic microparticle in a viscous fluid medium.

This work presents three-dimensional (3D) numerical analysis of acoustic radiation force on an elastic microsphere suspended in a viscous fluid. Acoustophoresis of finite-sized, neutrally buoyant, nearly incompressible soft particles may improve by orders of magnitude and change directions when going through resonant vibrations. These findings offer the potential to manipulate and separate microparticles based on their resonance frequency.

Transient Strain-Induced Electronic Structure Modulation in a Semiconducting Polymer Imaged by Scanning Ultrafast Electron Microscopy.

Understanding the optoelectronic properties of semiconducting polymers under external strain is essential for their applications in flexible devices. Although prior studies have highlighted the impact of static and macroscopic strains, assessing the effect of a local transient deformation before structural relaxation occurs remains challenging. Here, we employ scanning ultrafast electron microscopy (SUEM) to image the dynamics of a photoinduced transient strain in the semiconducting polymer poly(3-hexylthiophene) (P3HT).

Disposable photonics for cost-effective clinical bioassays: application to COVID-19 antibody testing.

Decades of research have shown that biosensors using photonic circuits fabricated using CMOS processes can be highly sensitive, selective, and quantitative. Unfortunately, the cost of these sensors combined with the complexity of sample handling systems has limited the use of such sensors in clinical diagnostics. We present a new "disposable photonics" sensor platform in which rice-sized (1 × 4 mm) silicon nitride ring resonator sensor chips are paired with plastic micropillar fluidic cards for sample handling and optical detection.

Toward optimal acoustophoretic microparticle manipulation by exploiting asymmetry.

The performance of a micro-acousto-fluidic device designed for microparticle trapping is simulated using a three-dimensional (3D) numerical model. It is demonstrated by numerical simulations that geometrically asymmetric architecture and actuation can increase the acoustic radiation forces in a liquid-filled cavity by almost 2 orders of magnitude when setting up a standing pressure half wave in a microfluidic chamber. Similarly, experiments with silicon-glass devices show a noticeable improvement in acoustophoresis of 20-μm silica beads in water when asymmetric devices are used.

Detection and classification of fentanyl and its precursors by surface-enhanced Raman spectroscopy.

Fentanyl and its analogs have been at the center of the opioid epidemic currently wreaking havoc in the United States. One major element in the opioid crisis is the growing number of clandestine fentanyl labs being reported by enforcement agencies. The development of new analytical methods for detecting and identifying fentanyl and its congeners is among the useful tools in our goal to limit the use of this dangerous family of narcotics.

Microfluidic analysis of fentanyl-laced heroin samples by surface-enhanced Raman spectroscopy in a hydrophobic medium.

Opioid overdose deaths resulting from heroin contaminated with the potent opioid agonist fentanyl, are currently a serious public health issue. A rapid and reliable method for identifying fentanyl-laced heroin could lead to reduced opioid overdose. Herein, we describe a strategy for detecting fentanyl at low concentrations in the presence of heroin, based on the significant hydrophobicity of fentanyl compared to heroin hydrochloride, by preferentially extracting trace concentrations of fentanyl using ultrasound-assisted emulsification microextraction using octanol as the extracting phase.

Fluorescence-Based Observation of Transient Electrochemical and Electrokinetic Effects at Nanoconfined Bipolar Electrodes.

Bipolar electrodes (BPEs) are conductors that, when exposed to an electric field, polarize and promote the accumulation of counterionic charge near their poles. The rich physics of electrokinetic behavior near BPEs has not yet been rigorously studied, with our current understanding of such bipolar effects being restricted to steady-state conditions (under constant applied fields). Here, we reveal the dynamic electrokinetic and electrochemical phenomena that occur near nanoconfined BPEs throughout all stages of a reaction.

Quantitative surface-enhanced Raman spectroscopy chemical analysis using citrate as an in situ calibrant.

Direct detection, or inferring the presence of illicit substances, is of great forensic and toxicological value. Surface-enhanced Raman spectroscopy (SERS) has been shown capable of detecting such molecules in a quick and sensitive manner. Herein we describe an analysis strategy for quantitation of low concentrations of three analytes (methamphetamine, cocaine, and papaverine) by SERS analysis using the citrate capping agent that initially saturates the silver nanoparticles' surface as an in situ standard.

Dielectrophoretic Nanoparticle Aggregation for On-Demand Surface Enhanced Raman Spectroscopy Analysis.

Rapid chemical identification of drugs of abuse in biological fluids such as saliva is of growing interest in healthcare and law enforcement. Accordingly, a label-free detection platform that accepts biological fluid samples is of great practical value. We report a microfluidics-based dielectrophoresis-induced surface enhanced Raman spectroscopy (SERS) device, which is capable of detecting physiologically relevant concentrations of methamphetamine in saliva in under 2 min.

Screening for canine transitional cell carcinoma (TCC) by SERS-based quantitative urine cytology.

Canine lower urinary tract neoplasia is a clinically important disease process that has high mortality due to late stage diagnosis and poorly durable response to treatment. Non-invasive diagnostic techniques (e.g.

Detection of Papaverine for the Possible Identification of Illicit Opium Cultivation.

Papaverine is a non-narcotic alkaloid found endemically and uniquely in the latex of the opium poppy. It is normally refined out of the opioids that the latex is typically collected for, hence its presence in a sample is strong prima facie evidence that the carrier from whom the sample was collected is implicated in the mass cultivation of poppies or the collection and handling of their latex. We describe an analysis technique combining surface-enhanced Raman spectroscopy (SERS) with microfluidics for detecting papaverine at low concentrations and show that its SERS spectrum has unique spectroscopic features that allows its detection at low concentrations among typical opioids.

Optimization of Surface-Enhanced Raman Spectroscopy Conditions for Implementation into a Microfluidic Device for Drug Detection.

A microfluidic device is being developed by University of California-Santa Barbara as part of a joint effort with the United States Army to develop a portable, rapid drug detection device. Surface-enhanced Raman spectroscopy (SERS) is used to provide a sensitive, selective detection technique within the microfluidic platform employing metallic nanoparticles as the SERS medium. Using several illicit drugs as analytes, the work presented here describes the efforts of the Edgewood Chemical Biological Center to optimize the microfluidic platform by investigating the role of nanoparticle material, nanoparticle size, excitation wavelength, and capping agents on the performance, and drug concentration detection limits achievable with Ag and Au nanoparticles that will ultimately be incorporated into the final design.

An electrical probe of the phonon mean-free path spectrum.

Most studies of the mean-free path accumulation function (MFPAF) rely on optical techniques to probe heat transfer at length scales on the order of the phonon mean-free path. In this paper, we propose and implement a purely electrical probe of the MFPAF that relies on photo-lithographically defined heater-thermometer separation to set the length scale. An important advantage of the proposed technique is its insensitivity to the thermal interfacial impedance and its compatibility with a large array of temperature-controlled chambers that lack optical ports.

Electrophoretic mobility of spherical particles in bounded domain.

In this study, we improve on our 3D steady-state model of electrophoretic motion of spherical particles in bounded fluidic channels (Liu et al., 2014) to include the effect of nonsymmetric electrolytes, and further validate this improved model with detailed comparisons to experimental data. Specifically, we use the experimentally-measured particle mobilities from the work of Semenov et al.

Detection of low concentrations of ampicillin in milk.

Ampicillin, a common antibiotic, is detected at trace concentrations in milk using surface enhanced Raman spectroscopy in a microfluidic device, using less than 20 μL of sample, in 10 minutes, with minimal off-chip preparation. The device is configured so as to favor the interaction of the analyte with colloidal silver, and the optimization of the aggregation of the silver nanoparticles so as to increase the SERS intensity and the consequential sensitivity of analyte detection.

Rapid identification by surface-enhanced Raman spectroscopy of cancer cells at low concentrations flowing in a microfluidic channel.

Reliable identification and collection of cells from bodily fluids is of growing interest for monitoring patient response to therapy and for early detection of disease or its recurrence. We describe a detection platform that combines microfluidics with surface-enhanced Raman spectroscopy (SERS) for the identification of individual mammalian cells continuously flowing in a microfluidics channel. A mixture of cancerous and noncancerous prostate cells was incubated with SERS biotags (SBTs) developed and synthesized by us, then injected into a flow-focused microfluidic channel, which forces the cells into a single file.

Convective flows in evaporating sessile droplets.

The evaporation rate and internal convective flows of a sessile droplet with a pinned contact line were formulated and investigated numerically. We developed and analyzed a unified numerical model that includes the effects of temperature, droplet volume, and contact angle on evaporation rate and internal flows. The temperature gradient on the air/liquid interface causes an internal flow due to Marangoni stress, which provides good convective mixing within the droplet, depending upon Marangoni number.

Discrete free-surface millifluidics for rapid capture and analysis of airborne molecules using surface-enhanced Raman spectroscopy.

A lithography-free, low-cost, free-surface millifluidic device is reported using discrete liquid interfaces for capturing and detecting gas-phase analyte molecules at low partial pressures out of a gas flow of time-varying composition. The architecture, based on segmented flow, consists of alternating regions of liquid and gas wherein the liquid regions contain surface-enhanced Raman spectroscopy (SERS)-active silver nanoparticles, while the gas regions contain trace quantities of vapor-phase analyte, thereby controlling and optimizing transport and mixing of the gas-phase analyte with the liquid phase. Once absorbed in the liquid phase, the entrained analyte molecules induce aggregation of the aqueous silver nanoparticles.

Aggregation kinetics of SERS-active nanoparticles in thermally stirred sessile droplets.

The aggregation kinetics of silver nanoparticles in sessile droplets were investigated both experimentally and through numerical simulations as a function of temperature gradient and evaporation rate, in order to determine the hydrodynamic and aggregation parameters that lead to optimal surface-enhanced Raman spectroscopic (SERS) detection. Thermal gradients promote effective stirring within the droplet. The aggregation reaction ceases when the solvent evaporates forming a circular stain consisting of a high concentration of silver nanoparticle aggregates, which can be interrogated by SERS leading to analyte detection and identification.

Rapid detection of drugs of abuse in saliva using surface enhanced Raman spectroscopy and microfluidics.

We present a microfluidic device that detects trace concentrations of drugs of abuse in saliva within minutes using surface-enhanced Raman spectroscopy (SERS). Its operation is demonstrated using methamphetamine. The detection scheme exploits concentration gradients of chemicals, fostered by the laminar flow in the device, to control the interactions between the analyte, silver nanoparticles (Ag-NPs), and a salt.

Free-surface microfluidics/surface-enhanced Raman spectroscopy for real-time trace vapor detection of explosives.

The dominant physical transport processes are analyzed in a free-surface microfluidic and surface-enhanced Raman spectroscopy (SERS) chemical detection system. The analysis describes the characteristic fluid dynamics and mass transport effects occurring in a microfluidic detection system whose analyte absorption and concentration capability is designed to operate on principles inspired by canine olfaction. The detection system provides continuous, real-time monitoring of particular vapor-phase analytes at concentrations of 1 ppb.

Flow optimization study of a batch microfluidics PET tracer synthesizing device.

We present numerical modeling and experimental studies of flow optimization inside a batch microfluidic micro-reactor used for synthesis of human-scale doses of Positron Emission Tomography (PET) tracers. Novel techniques are used for mixing within, and eluting liquid out of, the coin-shaped reaction chamber. Numerical solutions of the general incompressible Navier Stokes equations along with time-dependent elution scalar field equation for the three dimensional coin-shaped geometry were obtained and validated using fluorescence imaging analysis techniques.

Microliter-bioreactor array with buoyancy-driven stirring for human hematopoietic stem cell culture.

This work presents the development of an array of bioreactors where finely controlled stirring is provided at the microliter scale (100-300 mul). The microliter-bioreactor array is useful for performing protocol optimization in up to 96 parallel experiments of hematopoietic stem cell (HSC) cultures. Exploring a wide range of experimental conditions at the microliter scale minimizes cost and labor.

A unified scaling model for flow through a lattice of microfabricated posts.

A scaling model is presented for low Reynolds number viscous flow within an array of microfabricated posts. Such posts are widely used in several lab-on-a-chip applications such as heat pipes, antibody arrays and biomolecule separation columns. Finite element simulations are used to develop a predictive model for pressure driven viscous flow through posts.