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. This concept has profound implications in cell and microparticle handling, 3D printing, and enrichment in lab-on-chip applications. The existing analytical body of work can predict spheroidal harmonics of an elastic sphere and acoustic radiation force based on monopole and dipole scatter in an ideal fluid. However, little attention is given to the complex interplay of resonant fluid and solid bodies that generate acoustic radiation. The finite element method is used to find resonant modes, damping factors, and acoustic forces of an elastic sphere subject to a standing acoustic wave. Under fundamental spheroidal modes, the radiation force fluctuates significantly around analytical values due to constructive or destructive scatter-incident wave interference. This suggests that for certain materials, relevant to acoustofluidic applications, particle resonances are an important scattering mechanism and design parameter. The 3D model may be applied to any number of particles regardless of geometry or background acoustic field.

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). We observe that the photoinduced SUEM contrast, corresponding to the local change of secondary electron emission, exhibits an unusual ring-shaped profile. We attribute the observation to the electronic structure modulation of P3HT caused by a photoinduced strain field owing to its low modulus and strong electron-lattice coupling, supported by a finite-element analysis. Our work provides insights into tailoring optoelectronic properties using transient mechanical deformation in semiconducting polymers and demonstrates the versatility of SUEM to study photophysical processes in diverse materials.

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. Herein we describe an analytical technique using surface-enhanced Raman spectroscopy (SERS) and a microfluidic device, for detecting fentanyl and two of its chemical precursors, despropionylfentanyl (4ANPP) and N-phenethyl-4-piperidinone (NPP). The vibrational spectra of this family of analytes are very similar, making them difficult to distinguish by traditional means. In addition to taking advantage of the sensitivity provided by SERS, we developed a chemometric approach utilizing a hierarchical partial least squares-discriminant analysis algorithm that allowed us to distinguish spectra that possess many similar features.

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. Microparticle acoustophoresis has an extensive array of applications in applied science fields ranging from life sciences to 3D printing. A more efficient and powerful particle manipulation system can boost the overall effectiveness of an acoustofluidic device. The numerical simulations are developed in the COMSOL Multiphysics® software package (COMSOL AB, Stockholm, Sweden). By monitoring the modes and magnitudes of simulated acoustophoretic fields in a relatively wide range of ultrasonic frequencies, a map of device performance is obtained. 3D resonant acoustophoretic fields are identified to quantify the improved performance of the chips with an asymmetric layout. Four different device designs are analyzed experimentally, and particle tracking experimental data qualitatively supports the numerical results.

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. Surface-enhanced Raman spectroscopy (SERS), is enabled by exposing the analyte to silver nanoparticle-coated SiO2 nanoparticles, designed to be stable in mixtures of octanol and ethanol. The sample is then loaded into an SU8/glass microfluidic device that is compatible with non-aqueous solutions. The SERS-active nanoparticles are aggregated by dielectrophoresis using microelectrodes embedded in the microfluidic channels, and the nanoparticle aggregates are interrogated using Raman spectroscopy. Using this method, we were able to reliably detect fentanyl from samples with as low as 1 : 10 000 (mol/mol) fentanyl-to-heroin ratio, improving the limits of detection of fentanyl-laced heroin samples by two orders of magnitude over current techniques. The described system could also be useful in chemical detection where rapid and robust preconcentration of trace hydrophobic analytes, and rapid SERS detection in non-aqueous solvents is indicated.

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. The citrate is subsequently displaced by the analyte to an extent dependent on the analyte's concentration in the analyte solution. A general model for the competitive adsorption of citrate and a target analyte was developed and used to determine the relative concentrations of the two species coexisting on the surface of the silver nanoparticles. To apply this model, classical least squares (CLS) was used to extract the relative SERS contribution of each of the two species in a given SERS spectrum, thereby accurately determining the analyte concentration in the sample solution. This approach, in essence, transforms citrate into a local standard against which the concentration of an analyte can be reliably determined.

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. In this device, iodide-modified silver nanoparticles are trapped and released on-demand using electrodes integrated in a microfluidic channel. Principal component analysis (PCA) is used to reliably distinguish methamphetamine-positive samples from the negative control samples. Passivation of the electrodes and flow channels minimizes microchannel fouling by nanoparticles, which allows the device to be cleared and reused multiple times.

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. dipstick test, urine cytology) currently have poor diagnostic value, while more invasive tests (e.g. cystoscopy and biopsy) are costly and often require general anesthesia. We have developed and herein describe a quantitative cytological analysis method based on the use of surface-enhanced Raman spectroscopy (SERS), for identifying cancerous transitional cells in urine using SERS biotags (SBTs) carrying the peptide PLZ4 (amino acid sequence cQDGRMGFc) that targets malignant transitional cells. By analyzing the ratio of the PLZ4-SBTs to an on board control we were able to show that transitional cells had significantly higher ratios (P < 0.05) in patients diagnosed with transitional cell carcinoma (TCC) than in healthy samples.

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. The analysis requires approximately 2.5 min from sample loading to results, which is compatible with field use. The weak acid properties of papaverine hydrochloride were investigated, and Raman bands belonging to the protonated and unprotonated forms of the isoquinoline ring of papaverine were identified.

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. This study is particularly important as it lays out a systematic comparison of limits of detection and potential interferences from working with several nanoparticle capping agents-such as tannate, citrate, and borate-which does not seem to have been done previously as the majority of studies only concentrate on citrate as the capping agent. Morphine, cocaine, and methamphetamine were chosen as test analytes for this study and were observed to have limits of detection (LOD) in the range of (1.5-4.7) × 10-8 M (4.5-13 ng/mL), with the borate capping agent having the best performance.

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.

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. The resulting aggregates consisting of nanoparticles and adsorbed analyte molecules produce intense SERS spectra that reliably identify the absorbed analyte in real time. The approach can be used to determine the time-variable trace chemical composition of a gas stream with applications in, for example, environmental monitoring and online industrial process monitoring, or as a SERS-based detector following gas chromatographic separation. The operation of the system is demonstrated using 4-aminobenzenethiol vapor at 750 ppb, and the detection response time is <2 min.

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. That system as developed was limited to singleplex assays due to its optical configuration. To enable multiplexing, we report a new approach addressing multiplex light I/O, in which the outputs of individual grating couplers on a photonic chip are mapped to fibers in a fiber bundle. As demonstrated in the context of detecting antibody responses to influenza and SARS-CoV-2 antigens in human serum and saliva, this enables multiplexing in an inexpensive, disposable, and compact format.

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. We introduce the aggregation parameter, Γa ≡ τ(evap)/τ(a), which is the ratio of the evaporation to the aggregation time scales. For a well-stirred droplet, the optimal condition for SERS detection was found to be Γ(a,opt) = kc(NP)τ(evap) ≈ 0.3, which is a product of the dimerization rate constant (k), the concentration of nanoparticles (cNP), and the droplet evaporation time (τ(evap)). Near maximal signal (over 50% of maximum value) is observed over a wide range of aggregation parameters 0.05 < Γa < 1.25, which also defines the time window during which trace analytes can be easily measured. The results of the simulation were in very good agreement with experimentally acquired SERS spectra using gas-phase 1,4-benzenedithiol as a model analyte.

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. The system is designed with a large free-surface-to-volume ratio microfluidic channel which allows for polar or hydrophilic airborne analytes to readily be partitioned from the surrounding gas phase into the aqueous phase for detection. The microfluidic stream can concentrate certain molecules by up to 6 orders of magnitude, and SERS can enhance the Raman signal by 9-10 orders of magnitude for molecules residing in the so-called SERS "hot spots", providing extremely high detection sensitivity. The resulting vibrational spectra are sufficiently specific to identify the detected analyte unambiguously. Detection performance was demonstrated using a nominal 1 ppb, 2,4-dinitrotoluene (2,4-DNT) vapor stream entrained within N(2) gas. Applications to homeland security arise from the system's high sensitivity and its ability to provide highly reproducible, continuous chemical detection monitoring with minimal sampling requirements.

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. Utilizing the approach presented in this work, we were able to identify optimized geometrical and operational conditions for the micro-reactor in the absence of radioactive material commonly used in PET related tracer production platforms as well as evaluate the designed and fabricated micro-reactor using numerical and experimental validations.

Photoreduction at a distance: facile, nonlocal photoreduction of Ag ions in solution by plasmon-mediated photoemitted electrons.

Surface-immobilized, densely packed gold nanoparticles in contact with aqueous silver ions and exposed to red light rapidly photoreduce silver ions in solution producing radially symmetric metal deposits with diameters many times larger than the diameter of the illuminating laser beam. The average particle sizes in the deposit increase with radial distance from the center of the deposit. This reduction-at-a-distance effect arises from surface-plasmon-mediated photoemission, with the photoemitted electrons conducting along percolating silver pathways, reducing silver ions along these conducting channels and especially at their periphery, thereby propagating the effect of the illuminating laser outward.

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. We demonstrate the utility of the platform in the context of detecting human antibodies to SARS-CoV-2, both in convalescent COVID-19 patients and for subjects undergoing vaccination. Given its ability to provide quantitative data on human samples in a simple, low-cost single-use format, we anticipate that this platform will find broad utility in clinical diagnostics for a broad range of assays.

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. The results indicate that the flow rate per unit width scales as approximately h1.17g1.33/d0.5 where h is the post height, d post diameter and g is the spacing between the posts. These results compare favorably to theoretical limits. The scaling is extended to capillary pressure driven viscous flows. This unified model is the first report of a scaling that incorporates both viscous and capillary forces in the microfabricated post geometry. The model is consistent with Washburn dynamics and was experimentally validated to within 8% using wetting on microfabricated silicon posts.

Free-surface microfluidic control of surface-enhanced Raman spectroscopy for the optimized detection of airborne molecules.

We present a microfluidic technique for sensitive, real-time, optimized detection of airborne water-soluble molecules by surface-enhanced Raman spectroscopy (SERS). The method is based on a free-surface fluidic device in which a pressure-driven liquid microchannel flow is constrained by surface tension. A colloidal suspension of silver nanoparticles flowing through the microchannel that is open to the atmosphere absorbs gas-phase 4-aminobenzenethiol (4-ABT) from the surrounding environment. As surface ions adsorbed on the colloid nanoparticles are substituted by 4-ABT, the colloid aggregates, forming SERS "hot spots" whose concentrations vary predictably along the microchannel flow. 4-ABT confined in these hot spots produces SERS spectra of very great intensity. An aggregation model is used to account quantitatively for the extent of colloid aggregation as determined from the variation of the SERS intensity measured as a function of the streamwise position along the microchannel, which also corresponds to nanoparticle exposure time. This allows us to monitor simultaneously the nanoparticle aggregation process and to determine the location at which the SERS signal is optimized.