Acoustofluidic lysis of cancer cells and Raman spectrum profiling.

The lysis of cancer cells inside a sessile droplet was performed using traveling surface acoustic waves (SAWs) without any chemical reagents. Raman spectrum profiling was then carried out to explore detailed cell-derived data. The Rayleigh waves formed by an interdigital transducer were made to propagate along the surface of an LiNbO3 substrate. Polystyrene microparticles (PSMPs) were used to establish mechanical cell lysis effectively, and gold nanoparticles (AuNPs) were added to enhance the Raman signals from the lysed cells by SAWs. The lysis efficiency was evaluated according to the size and concentration of the PSMPs in experiments where the frequency was varied. Lysis occurred mainly by mechanical collision using PSMPs in a high-frequency domain, and the lysis efficiency was improved by increasing the application time and the energy density of the SAWs. Raman signals from the lysed cells were greatly enhanced by nanogaps formed by the AuNPs, which were evenly distributed irrespective of the SAWs through the frequency-independent behavior of the AuNPs. Finally, detailed Raman spectra of MDA-MB-231, malignant breast cancer cells, were acquired, and various organic matter-derived peaks were observed. The 95% confidence region for cells subjected to lysis was more widely distributed than that of cells not subjected to lysis. The proposed SAW platform is expected to facilitate the detection of small quantities and to be applied in biomedical applications.

Hydrodynamic interaction of dorsal fin and caudal fin in swimming tuna.

Tuna, which are known for high-performance swimming, possess a large crescent dorsal fin (DF) and a caudal fin (CF) that differ from those of other fishes. The hydrodynamic interaction between the DF and CF in tuna, which are represented by two tandem 3D flapping plates, is numerically explored in the present study. Hydrodynamic properties and wake structures of the models with and without a DF are compared to investigate the effects of the DF. The thrust on the CF is substantially enhanced by the DF, whereas the force on the DF is not affected by the CF. The constructive interaction between the leading-edge vortex (LEV) on the CF and the vortices shed from the dorsal fin (DFVs) is identified from 3D wake topology and 2D vorticity distributions. The circulation of spanwise vorticity quantitatively reveals that the LEV on the CF is strengthened by the same-signed DFV. The effect of the flapping phase of the CF is examined. The DF-CF interaction is sensitive to the flapping phase at a short spacing, whereas a long spacing between the two fins enables a robust constructive interaction in tuna swimming. A systematic study is carried out to explore the effects of the Strouhal number (St) and the Reynolds number (Re) on the interaction of the fins. The enhancement of thrust due to the DF is diminished at St = 0.63, whereas the Re does not substantially influence the constructive DF-CF interaction.

Acoustofluidic Stimulation of Functional Immune Cells in a Microreactor.

The cytotoxic response of natural killer (NK) cells in a microreactor to surface acoustic waves (SAWs) is investigated, where the SAWs produce an acoustic streaming flow. The Rayleigh-type SAWs form by an interdigital transducer propagated along the surface of a piezoelectric substrate in order to allow the dynamic stimulation of functional immune cells in a noncontact and rotor-free manner. The developed acoustofluidic microreactor enables a dynamic cell culture to be set up in a miniaturized system while maintaining the performance of agitating media. The present SAW system creates acoustic streaming flow in the cylindrical microreactor and applies flow-induced shear stress to the cells. The suspended NK cells are found to not be damaged by the SAW operation of the adjusted experimental setup. Suspended NK cell aggregates subjected to an SAW treatment show increased intracellular Ca2+ concentrations. Simultaneously treating the NK cells with SAWs and protein kinase C activator enhances the lysosomal protein expressions of the cells and the cell-mediated cytotoxicity against target tumor cells. These have important implications by showing that acoustically actuated system allows dynamic cell culture without cell damages and further alters cytotoxicity-related cellular activities.

Manipulation of cancer cells in a sessile droplet via travelling surface acoustic waves.

The behaviours of microparticles inside a sessile droplet actuated by surface acoustic waves (SAWs) were investigated, where the SAWs produced an acoustic streaming flow and imparted an acoustic radiation force on the microparticles. The Rayleigh waves formed by a comb-like interdigital transducer were made to propagate along the surface of a LiNbO3 substrate in order to allow the manipulation of microparticles in a label-free and non-contact manner. Polystyrene microparticles were first employed to describe the behaviours inside a sessile droplet. The influence of the volume of the sessile droplet on the behaviours of the microparticles was examined by changing the contact angle of the droplet. Next, cancer cells were suspended in a sessile droplet, and the influence of contact angle on the behaviours of the cancer cells was investigated. A long gelation time was afforded by using a PEGylated fibrin gel. A primary tumour was mimicked by patterning the cancer cells to be concentrated in the middle of the sessile droplet. The non-contact manipulation property of acoustic waves was indicated to be biocompatible and enabled a structure-free platform configuration. Three-dimensional aggregated culture models were observed to make the cancer cells display an elevated expression of E-cadherin. The efficacy of the anticancer drug tirapazamine increased in the aggregated cancer cells, attributed to the low levels of oxygen in this formation of cancer cells.

Antibiotic susceptibility test under a linear concentration gradient using travelling surface acoustic waves.

An efficient and accurate antibiotic susceptibility test (AST) is indispensable for measuring the antimicrobial resistance of pathogenic bacteria. A minimal inhibitory concentration (MIC) can be obtained without performing repeated dilutions of the antibiotic by forming a linear antibiotic concentration gradient in a microfluidic channel. We demonstrated a device designed to use travelling surface acoustic waves (TSAWs) to enable a rapid formation of an antibiotic gradient in a few seconds. The TSAWs produced by a focused interdigital transducer deposited on the surface of a piezoelectric (LiNbO3) substrate generated an acoustic streaming flow inside a microfluidic channel, which mixed confluent streams of antibiotics in a controlled fashion. The growth of bacteria exposed to the antibiotic gradient was determined by measuring the MIC, which was used as an indicator of the effectiveness of the AST. The concentration gradient produced using our device was linear, a feature that enhanced the reliability of measurements throughout the microchannel. Two ASTs, namely Pseudomonas aeruginosa against gentamicin and levofloxacin were chosen for the case of slowly proliferating bacteria, and one AST, namely Escherichia coli against gentamicin, were chosen for the rapidly proliferating case. Appropriate antibiotic doses for Pseudomonas aeruginosa and Escherichia coli were each obtained in an efficient manner.

Acoustofluidic Separation of Proteins Using Aptamer-Functionalized Microparticles.

We propose an acoustofluidic method for the triseparation of proteins conjugated with aptamer-coated microparticles inside a microchannel. Traveling surface acoustic waves (TSAWs) produced from a slanted-finger interdigital transducer (SFIT) are used to separate the protein-loaded microparticles of different sizes via the TSAW-driven acoustic radiation force (ARF). The acoustofluidic device consists of an SFIT deposited onto a piezoelectric lithium niobate substrate and a polydimethylsiloxane (PDMS) microfluidic channel on top of the substrate. The TSAWs propagating on the substrate penetrate into the sample fluid flow, where the human protein-conjugated microparticles are suspended, inside the PDMS microchannel. The microparticles are subjected to the TSAW-driven ARF with varying magnitude depending on their size and thus flow along different streamlines, leading to triseparation of the proteins. In this work, we used two different-sized streptavidin-functionalized polystyrene (PS) microparticles to capture two kinds of aptamers (apt15 and aptD17.4), which were labeled with a respective biotin molecule at one end. The biotin ends of the aptamers were attached to the microparticles through streptavidin-biotin linkage, whereas the free ends of the aptamers were used to capture their target proteins of thrombin (th) and immunoglobulin E (IgE). The resultant PS-apt15-th and PS-aptD17.4-IgE complexes, as well as mCardinal2, were used for experimental demonstration of acoustofluidic triseparation of the human proteins. We achieved simultaneous separation of proteins of three kinds (th, IgE, and mCardinal2) for the first time via the TSAW-driven ARF in the proposed acoustofluidic device.

Acoustofluidic generation of droplets with tunable chemical concentrations.

The dynamic control of the chemical concentration within droplets is required in numerous droplet microfluidic applications. Here, we propose an acoustofluidic method for the generation of a library of aqueous droplets with the desired chemical concentrations in a continuous oil phase. Surface acoustic waves produced by a focused interdigital transducer interact with two parallel laminar streams with different chemical compositions. Coupling the acoustic waves with the flow streams results in the controlled acoustofluidic mixing of the aqueous solutions through the formation of acoustic streaming flow-induced microvortices. The mixed streams are split at a bifurcation, and one of the streams with a precisely controlled chemical concentration is fed into a T-junction to produce droplets with tunable chemical concentrations. The periodic acoustofluidic mixing of the aqueous streams enables the generation of a droplet library with a well-defined inter-droplet concentration gradient. The proposed method is a promising tool for the on-chip dynamic control of in-droplet chemical concentrations and for next-generation droplet microfluidic applications.

Control of solutal Marangoni-driven vortical flows and enhancement of mixing efficiency.

HYPOTHESIS: In droplet microfluidics applications, flow control and mixing in a small volume without any active external devices is a challenge. Vapor-mediated solutal Marangoni flows can be effectively generated by applying the vapor of a volatile liquid, which can be possibly controlled, and can eventually be used in a mixing enhancement device. EXPERIMENTS: We investigated and controlled vapor-mediated solutal Marangoni flows by varying the local surface tension. We systematically tested the effects of different volatile liquids and their vapor concentration on the flow pattern. Furthermore, by varying the number of vapor sources, we generated and controlled multiple vortices, and analyzed them by particle image velocimetry (PIV). The proposed method was applied to a mixing enhancement application. FINDINGS: We show that in addition to the surface tension of the volatile liquid, the vapor concentration also influenced the local surface tension along the interface, which in turn changed the internal flow velocity. To predict the flow velocity and oscillatory frequency of the solutal Marangoni flow, we developed a theoretical model based on scaling analysis that showed a good agreement with the experimental results. We believe that the current study will motivate low-cost and portable sample flow control and mixing systems in the near future.

Undulatory topographical waves for flow-induced foulant sweeping.

Diverse bioinspired antifouling strategies have demonstrated effective fouling-resistant properties with good biocompatibility, sustainability, and long-term activity. However, previous studies on bioinspired antifouling materials have mainly focused on material aspects or static architectures of nature without serious consideration of kinetic topographies or dynamic motion. Here, we propose a magnetically responsive multilayered composite that can generate coordinated, undulatory topographical waves with controlled length and time scales as a new class of dynamic antifouling materials. The undulatory surface waves of the dynamic composite induce local and global vortices near the material surface and thereby sweep away foulants from the surface, fundamentally inhibiting their initial attachment. As a result, the dynamic composite material with undulating topographical waves provides an effective means for efficient suppression of biofilm formation without surface modification with chemical moieties or nanoscale architectures.

Investigation of DPD transport properties in modeling bioparticle motion under the effect of external forces: Low Reynolds number and high Schmidt scenarios.

We have used a dissipative particle dynamics (DPD) model to study the movement of microparticles in a microfluidic device at extremely low Reynolds number (Re). The particles, immersed in a medium, are transported in the microchannel by a flow force and deflected transversely by an external force along the way. An in-house Fortran code is developed to simulate a two-dimensional fluid flow using DPD at Re ≥ 0.0005, which is two orders of magnitude less than the minimum Re value previously reported in the DPD literature. The DPD flow profile is verified by comparing it with the exact solution of Hagen-Poiseuille flow. A bioparticle based on a rigid spring-bead model is introduced in the DPD fluid, and the employed model is verified via comparing the velocity profile past a stationary infinite cylinder against the profile obtained via the finite element method. Moreover, the drag force and drag coefficient on the stationary cylinder are also computed and compared with the reported literature results. Dielectrophoresis (DEP) is investigated as a case study for the proposed DPD model to compute the trajectories of red blood cells in a microfluidic device. A mapping mechanism to scale the external deflecting force from the physical to DPD domain is performed. We designed and built our own experimental setup with the aim to compare the experimental trajectories of cells in a microfluidic device to validate our DPD model. These experimental results are used to investigate the dependence of the trajectory results on the Reynolds number and the Schmidt number. The numerical results agree well with the experiment results, and it is found that the Schmidt number is not a significant parameter for the current application; Reynolds numbers combined with the DEP-to-drag force ratio are the only important parameters influencing the behavior of particles inside the microchannel.

Microparticle self-assembly induced by travelling surface acoustic waves.

We present an acoustofluidic method based on travelling surface acoustic waves (TSAWs) to induce self-assembly of microparticles inside a microfluidic channel. The particles are trapped above an interdigitated transducer, placed directly beneath the microchannel, by the TSAW-based direct acoustic radiation force (ARF). This approach was applied to trap 10 µm polystyrene particles, which were pushed towards the ceiling of the microchannel by 72 MHz TSAWs to form single- and multiple-layer colloidal structures. The repair of cracks and defects within the crystal lattice occurs as part of the self-assembly process. The sample flow through the first inlet can be switched with a buffer flow through the second inlet to control the number of particles assembled in the crystalline structure. The constant flow-induced Stokes drag force on the particles is balanced by the opposing TSAW-based ARF. This force balance is essential for the acoustics-based self-assembly of microparticles inside the microchannel. Moreover, we studied the effects of varying input voltage and fluid flow rate on the position and shape of the colloidal structure. The active self-assembly of microparticles into crystals with multiple layers can be used in the bottom-up fabrication of colloidal structures with dimensions greater than 500 µm × 500 µm, which is expected to have important applications in various fields.

In-droplet microparticle washing and enrichment using surface acoustic wave-driven acoustic radiation force.

Washing and enrichment of particles and cells are crucial sample preparation procedures in biomedical and biochemical assays. On-chip in-droplet microparticle washing and enrichment have been pursued but remained problematic due to technical difficulties, especially simultaneous and precise control over the droplet interface and in-droplet samples. Here, we have achieved a breakthrough in label-free, continuous, on-demand, in-droplet microparticle washing and enrichment using surface acoustic waves. When exposed to the acoustic field, the droplet and suspended particles experience acoustic radiation force arising from inhomogeneous wave scattering at the liquid/liquid and liquid/solid interfaces. Based on these acoustophoretic phenomena, we have demonstrated in-droplet microparticle washing and enrichment in an acoustofluidic device. We expect that the proposed acoustic method will offer new perspectives to sample washing and enrichment by performing the operation in microscale droplets.

Spontaneous Additive Nanopatterning from Solution Route Using Selective Wetting.

Nanopatterns of functional materials have successfully led innovations in a wide range of fields, but further exploration of their full potential has often been limited because of complex and cost-inefficient patterning processes. We here propose an additive nanopatterning process of functional materials from solution route using selective wetting phenomenon. The proposed process can produce nanopatterns as narrow as 150 nm with high yield over large area at ultrahigh process speed, that is, the speed of solution dragging, of up to ca. 4.6 m·min-1. The process is highly versatile that it can utilize a wide range of solution materials, control vertical structures including pattern thickness and multistacks, and produce nanopatterns on various substrates with emerging form factors such as foldability and disposability. The solution patterning in nanoscale by selective wetting is enabled by corresponding surface energy patterns in high contrast that are achieved by one-step imprinting onto hydrophobic/hydrophilic bilayers. The mechanisms and control parameters for the solution patterning are revealed by fluid-dynamic simulation. With the aforementioned advantages, we demonstrate 25 400 pixel-per-inch light-emitting pixel arrays and a plasmonic color filter of 10 cm × 10 cm area on a plastic substrate as potential applications.

Sheathless Focusing and Separation of Microparticles Using Tilted-Angle Traveling Surface Acoustic Waves.

Sheathless focusing and separation of microparticles is an important preprocessing step in various biochemical assays in which enriched sample isolation is critical. Most of the previous microfluidic particle separation techniques have used sheath flows to achieve efficient sample focusing. The sheath flow dilutes the analyte and requires additional microchannels and accurate flow control. We demonstrated a tilted-angle traveling surface acoustic wave (taTSAW)-based sheathless focusing and separation of particles in a continuous flow. The proposed device consists of a piezoelectric substrate with a pair of interdigitated transducers (IDTs) deposited at two different angles relative to the flow direction. A Y-shaped polydimethylsiloxane (PDMS) microchannel having one inlet and two outlet ports was positioned on top of the IDTs such that the acoustic energy coupling into the fluid was maximized and wave attenuation by the PDMS walls was minimized. The two IDTs independently produced high-frequency taTSAWs, which propagated at ±30° with respect to the flow direction and imparted a direct acoustic radiation force onto the target particles. A sample mixture of 4.8 and 3.2 µm particles was focused and then separated by the actuation of the IDTs at 194 and 136 MHz frequencies, respectively, without using an additional sheath flow. The proposed taTSAW-based particle separation device offered a high purity >99% at the both outlets over a wide range of flow speeds (up to 83.3 mm/s).

Vertical Hydrodynamic Focusing and Continuous Acoustofluidic Separation of Particles via Upward Migration.

A particle suspended in a fluid within a microfluidic channel experiences a direct acoustic radiation force (ARF) when traveling surface acoustic waves (TSAWs) couple with the fluid at the Rayleigh angle, thus producing two components of the ARF. Most SAW-based microfluidic devices rely on the horizontal component of the ARF to migrate prefocused particles laterally across a microchannel width. Although the magnitude of the vertical component of the ARF is more than twice the magnitude of the horizontal component, it is long ignored due to polydimethylsiloxane (PDMS) microchannel fabrication limitations and difficulties in particle focusing along the vertical direction. In the present work, a single-layered PDMS microfluidic chip is devised for hydrodynamically focusing particles in the vertical plane while explicitly taking advantage of the horizontal ARF component to slow down the selected particles and the stronger vertical ARF component to push the particles in the upward direction to realize continuous particle separation. The proposed particle separation device offers high-throughput operation with purity >97% and recovery rate >99%. It is simple in its fabrication and versatile due to the single-layered microchannel design, combined with vertical hydrodynamic focusing and the use of both the horizontal and vertical components of the ARF.

Microfluidic flow switching via localized acoustic streaming controlled by surface acoustic waves.

We propose an acoustic flow switching device that utilizes high-frequency surface acoustic waves (SAWs) produced by a slanted-finger interdigitated transducer. As the acoustic field induced by the SAWs was attenuated in the fluid, it produced an acoustic streaming flow in the form of a pair of symmetrical microvortices, which induced flow switching between two fluid streams in a controlled manner. The microfluidic device was composed of a piezoelectric substrate attached to a polydimethylsiloxane (PDMS) microchannel having an H-shaped junction that connected two fluid streams in the middle. The two immiscible fluids, separated by the PDMS wall, flowed in parallel, briefly came in contact at the junction, and separated again into the downstream microchannels. The acoustic streaming flow induced by the SAWs rotated the fluid streams within the microchannel cross-section, thereby altering the respective positions of the two fluids and directing them into the opposite flow paths. The characteristics of the flow switching mechanism were investigated by tuning the input voltage and the flowrates. On-demand acoustic flow switching was successfully achieved without additional moving parts inside the microchannel. This technique may be useful for fundamental studies that integrate complex experimental platforms into a single chip.

On-demand acoustic droplet splitting and steering in a disposable microfluidic chip.

On-chip droplet splitting is one of the fundamental droplet-based microfluidic unit operations to control droplet volume after production and increase operational capability, flexibility, and throughput. Various droplet splitting methods have been proposed, and among them the acoustic droplet splitting method is promising because of its label-free operation without any physical or thermal damage to droplets. Previous acoustic droplet splitting methods faced several limitations: first, they employed a cross-type acoustofluidic device that precluded multichannel droplet splitting; second, they required irreversible bonding between a piezoelectric substrate and a microfluidic chip, such that the fluidic chip was not replaceable. Here, we present a parallel-type acoustofluidic device with a disposable microfluidic chip to address the limitations of previous acoustic droplet splitting devices. In the proposed device, an acoustic field is applied in the direction opposite to the flow direction to achieve multichannel droplet splitting and steering. A disposable polydimethylsiloxane microfluidic chip is employed in the developed device, thereby removing the need for permanent bonding and improving the flexibility of the droplet microfluidic device. We experimentally demonstrated on-demand acoustic droplet bi-splitting and steering with precise control over the droplet splitting ratio, and we investigated the underlying physical mechanisms of droplet splitting and steering based on Laplace pressure and ray acoustics analyses, respectively. We also demonstrated droplet tri-splitting to prove the feasibility of multichannel droplet splitting. The proposed on-demand acoustic droplet splitting device enables on-chip droplet volume control in various droplet-based microfluidic applications.

A Pumpless Acoustofluidic Platform for Size-Selective Concentration and Separation of Microparticles.

We have designed a pumpless acoustofluidic device for the concentration and separation of different sized particles inside a single-layered straight polydimethylsiloxane (PDMS) microfluidic channel. The proposed device comprises two parallel interdigitated transducers (IDTs) positioned underneath the PDMS microchannel. The IDTs produce high-frequency surface acoustic waves that generate semipermeable virtual acoustic radiation force field walls that selectively trap and concentrate larger particles at different locations inside the microchannel and allow the smaller particles to pass through the acoustic filter. The performance of the acoustofluidic device was first characterized by injecting into the microchannel a uniform flow of suspended 9.9 µm diameter particles with various initial concentrations (as low as 10 particles/mL) using a syringe pump. The particles were trapped with ∼100% efficiency by a single IDT actuated at 73 MHz. The acoustofluidic platform was used to demonstrate the pumpless separation of 12.0, 4.8, and 2.1 µm microparticles by trapping the 12 and 4.8 µm particles using the two IDTs actuated at 73 and 140 MHz, respectively. However, most of the 2.1 µm particles flowed over the IDTs unaffected. The acoustofluidic device was capable of rapidly processing a large volume of sample fluid pumped through the microchannel using an external syringe pump. A small volume of the sample fluid was processed through the device using a capillary flow and a hydrodynamic pressure difference that did not require an external pumping device.

Acoustic Wave-Driven Functionalized Particles for Aptamer-Based Target Biomolecule Separation.

We developed a hybrid microfluidic device that utilized acoustic waves to drive functionalized microparticles inside a continuous flow microchannel and to separate particle-conjugated target proteins from a complex fluid. The acoustofluidic device is composed of an interdigitated transducer that produces high-frequency surface acoustic waves (SAW) and a polydimethylsiloxane (PDMS) microfluidic channel. The SAW interacted with the sample fluid inside the microchannel and deflected particles from their original streamlines to achieve separation. Streptavidin-functionalized polystyrene (PS) microparticles were used to capture aptamer (single-stranded DNA) labeled at one end with a biotin molecule. The free end of the customized aptamer15 (apt15), which was attached to the microparticles via streptavidin-biotin linkage to form the PS-apt15 conjugate, was used to capture the model target protein, thrombin (th), by binding at exosite I to form the PS-apt15-th complex. We demonstrated that the PS-apt15 conjugate selectively captured thrombin molecules in a complex fluid. After the PS-apt15-th complex was formed, the sample fluid was pumped through a PDMS microchannel along with two buffer sheath flows that hydrodynamically focused the sample flow prior to SAW exposure for PS-apt15-th separation from the non-target proteins. We successfully separated thrombin from mCardinal2 and human serum using the proposed acoustofluidic device.

Comparison of Accuracy of One-Use Methods for Calculating Fractional Flow Reserve by Intravascular Optical Coherence Tomography to That Determined by the Pressure-Wire Method.

Although the identification of the hemodynamic significance of coronary lesions becomes important for revascularization strategy, the potential role of 3-dimensional high-resolution intracoronary optical coherence tomography (OCT) for predicting functional significance of coronary lesions remains unclear. We assessed the diagnostic performance of 2 computational approaches for deriving fractional flow reserve (FFR) from intravascular OCT images. We developed 2 methods to derive FFR-OCT by AFD (FFR-OCTAFD) and FFR-OCT by CFD (FFR-OCTCFD). Among 217 eligible patients between 2011 and 2014, 104 were included for data analysis (9 for derivation, 95 for validation). Luminal geometries from 3-dimensional OCT were used for both FFR-OCTAFD and FFR-OCTCFD calculations. The analytical fluid dynamics method calculated FFR from the blood flow resistance estimated using Poiseuille's law. For computational fluid dynamics, we numerically solved the Navier-Stokes equation in a steady-state flow with the distal porous media model for the capillary vessels. We examined the diagnostic performance of FFR-OCTAFD and FFR-OCTCFD compared with the pressure-wire measured FFR. The accuracy, sensitivity, specificity, PPV, and NPV were 86%, 65%, 94%, 81%, and 88% for FFR-OCTAFD and 86%, 73%, 91%, 76%, and 90% for FFR-OCTCFD. The area under the curve of the receiver-operating characteristic curve was 0.88 for FFR-OCTAFD and 0.86 for FFR-OCTCFD. FFR-OCTAFD and FFR-OCTCFD showed a strong linear correlation with the measured FFR (r = 0.631; p <0.001, r = 0.655; p <0.001, respectively). FFR derived from high-resolution volumetric OCT images showed high diagnostic performance for the detection of coronary ischemia. In conclusion, OCT-derived FFR may be useful for guiding the management of coronary artery disease.