Estimation and Validation of Arterial Blood Pressure Using Photoplethysmogram Morphology Features in Conjunction With Pulse Arrival Time in Large Open Databases.

Although various predictors and methods for BP estimation have been proposed, differences in study designs have led to difficulties in determining the optimal method. This study presents analyses of BP estimation methods using 2.4 million cardiac cycles of two commonly used non-invasive biosignals, electrocardiogram (ECG) and photoplethysmogram (PPG), from 1376 surgical patients. Feature selection methods were used to determine the best subset of predictors from a total of 42 including PAT, heart rate (HR), and various PPG morphology features, and BP estimation models constructed using linear regression (LR), random forest (RF), artificial neural network (ANN), and recurrent neural network (RNN) were evaluated. 28 features out of 42 were determined as suitable for BP estimation, in particular two PPG morphology features outperformed PAT, which has been conventionally seen as the best non-invasive indicator of BP. By modelling the low frequency component of BP using ANN and the high frequency component using RNN with the selected predictors, mean errors of 0.05 ± 6.92 mmHg for systolic BP, and -0.05 ± 3.99 mmHg for diastolic BP were achieved. External validation of the model using another biosignal database consisting of 334 intensive care unit patients led to similar results, satisfying three standards for accuracy of BP monitors. The results indicate that the proposed method can contribute to the realization of ubiquitous non-invasive continuous BP monitoring.

Reconstruction of 12-Lead Electrocardiogram from a Three-Lead Patch-Type Device Using a LSTM Network.

Reconstructing a standard 12-lead electrocardiogram (ECG) from signals received from electrodes packed into a patch-type device is a challenging task in the field of medical instrumentation. All attempts to obtain a clinically valid 12-lead ECG using a patch-type device were not satisfactory. In this study, we designed the hardware for a three-lead patch-type ECG device and employed a long short-term memory (LSTM) network that can overcome the limitations of the linear regression algorithm used for ECG reconstruction. The LSTM network can overcome the issue of reduced horizontal components of the vector in the electric signal obtained from the patch-type device attached to the anterior chest. The reconstructed 12-lead ECG that uses the LSTM network was tested against a standard 12-lead ECG in 30 healthy subjects and ECGs of 30 patients with pathologic findings. The average correlation coefficient of the LSTM network was found to be 0.95. The ability of the reconstructed ECG to detect pathologic abnormalities was identical to that of the standard ECG. In conclusion, the reconstruction of a standard 12-lead ECG using a three-lead patch-type device is feasible, and such an ECG is an equivalent alternative to a standard 12-lead ECG.

Analysis of Pulse Arrival Time as an Indicator of Blood Pressure in a Large Surgical Biosignal Database: Recommendations for Developing Ubiquitous Blood Pressure Monitoring Methods.

As non-invasive continuous blood pressure monitoring (NCBPM) has gained wide attraction in the recent decades, many pulse arrival time (PAT) or pulse transit time (PTT) based blood pressure (BP) estimation studies have been conducted. However, most of the studies have used small homogeneous subject pools to generate models of BP based on particular interventions for induced hemodynamic change. In this study, a large open biosignal database from a diverse group of 2309 surgical patients was analyzed to assess the efficacy of PAT, PTT, and confounding factors on the estimation of BP. After pre-processing the dataset, a total of 6,777,308 data pairs of BP and temporal features between electrocardiogram (ECG) and photoplethysmogram (PPG) were extracted and analyzed. Correlation analysis revealed that PAT or PTT extracted from the intersecting-tangent (IT) point of PPG showed the highest mean correlation to BP. The mean correlation between PAT and systolic blood pressure (SBP) was -0.37 and the mean correlation between PAT and diastolic blood pressure (DBP) was -0.30, outperforming the correlation between BP and PTT at -0.12 for SBP and -0.11 for DBP. A linear model of BP with a simple calibration method using PAT as a predictor was developed which satisfied international standards for automatic oscillometric BP monitors in the case of DBP, however, SBP could not be predicted to a satisfactory level due to higher errors. Furthermore, multivariate regression analyses showed that many confounding factors considered in previous studies had inconsistent effects on the degree of correlation between PAT and BP.

The importance of sensor contacting force for predicting fluid responsiveness in children using respiratory variations in pulse oximetry plethysmographic waveform.

Predicting fluid responsiveness is crucial for adequate fluid management. Respiratory variations in pulse oximetry plethysmographic waveform amplitude (ΔPOP) are used to predict fluid responsiveness, but show inconsistent results when used for children. Contacting force between the measurement site and sensor can affect the ΔPOP value, thereby hindering its reliability as an indicator. We studied the influence of contacting force on the efficacy of ΔPOP as a fluid responsiveness indicator in children. In total, 43 mechanically ventilated children aged 1 month-5 years were studied. After anesthetic induction, mechanical ventilation began with a tidal volume of 10 ml/kg. ΔPOP was calculated for five different contacting force groups (0-0.3N, 0.3-0.6N, 0.6-0.9N, 0.9-1.2N, and 1.2-1.5N) and individually adjusted contacting force. Pulse pressure variation (PPV), and ΔVpeak were recorded before and after volume expansion. Subjects were considered as fluid responders if volume expansion increased the stroke volume index (SVI) by > 15%. Data from 38 patients were finally analyzed. A significant difference between the responders and non-responders was found only in ΔPOPs at 0.9-1.2N contacting force (P = 0.002) and individually adjusted contacting force (P < 0.000), while other contacting force groups did not show significant differences. ΔVpeak predicted a 15% increase in SVI (P = 0.008), whereas PPV did not. The ability of ΔPOP to predict fluid responsiveness depends on the contacting force in mechanically ventilated children. When contacting force is controlled to an adequate degree, the ability of ΔPOP to predict fluid responsiveness can be improved.

Time to consider the contact force during photoplethysmography measurement during pediatric anesthesia: A prospective, nonrandomized interventional study.

BACKGROUND: Respiratory variations in photoplethysmography amplitude enable volume status assessment. However, the contact force between the measurement site and sensor can affect photoplethysmography waveforms. We aimed to evaluate contact force effects on respiratory variations in photoplethysmography waveforms in children under general anesthesia. METHODS: Children aged 3-5 years were enrolled. After anesthetic induction, mechanical ventilation commenced at a tidal volume of 10 mL/kg. Photoplethysmographic signals were obtained in the supine position from the index finger using a force sensor-integrated clip-type photoplethysmography sensor that increased the contact force from 0-1.4 N for 20 respiratory cycles at each force. The AC amplitude (pulsatile component), DC amplitude (nonpulsatile component), AC/DC ratio, and respiratory variations in photoplethysmography amplitude were calculated. RESULTS: Data from 34 children were analyzed. Seven contact forces at 0.2-N increments were evaluated for each patient. The normalized AC amplitude increased maximally at a contact force of 0.4-0.6 N and decreased with increasing contact force. However, the normalized DC amplitude increased with a contact force exceeding 0.4 N. ΔPOP decreased slightly and increased from the point when the AC amplitude started to decrease as contact force increased. In a 0.2-1.2 N contact force range, significant changes in the normalized AC amplitude, normalized DC amplitude, AC/DC ratio, and respiratory variations in photoplethysmography amplitude were observed. CONCLUSION: Respiratory variations in photoplethysmography amplitude changed according to variable contact forces; therefore, these measurements may not reflect respiration-induced stroke volume variations. Clinicians should consider contact force bias when interpreting morphological data from photoplethysmography signals.

Novel blood pressure and pulse pressure estimation based on pulse transit time and stroke volume approximation.

BACKGROUND: Non-invasive continuous blood pressure monitors are of great interest to the medical community due to their value in hypertension management. Recently, studies have shown the potential of pulse pressure as a therapeutic target for hypertension, but not enough attention has been given to non-invasive continuous monitoring of pulse pressure. Although accurate pulse pressure estimation can be of direct value to hypertension management and indirectly to the estimation of systolic blood pressure, as it is the sum of pulse pressure and diastolic blood pressure, only a few inadequate methods of pulse pressure estimation have been proposed. METHODS: We present a novel, non-invasive blood pressure and pulse pressure estimation method based on pulse transit time and pre-ejection period. Pre-ejection period and pulse transit time were measured non-invasively using electrocardiogram, seismocardiogram, and photoplethysmogram measured from the torso. The proposed method used the 2-element Windkessel model to model pulse pressure with the ratio of stroke volume, approximated by pre-ejection period, and arterial compliance, estimated by pulse transit time. Diastolic blood pressure was estimated using pulse transit time, and systolic blood pressure was estimated as the sum of the two estimates. The estimation method was verified in 11 subjects in two separate conditions with induced cardiovascular response and the results were compared against a reference measurement and values obtained from a previously proposed method. RESULTS: The proposed method yielded high agreement with the reference (pulse pressure correlation with reference R ≥ 0.927, diastolic blood pressure correlation with reference R ≥ 0.854, systolic blood pressure correlation with reference R ≥ 0.914) and high estimation accuracy in pulse pressure (mean root-mean-squared error ≤ 3.46 mmHg) and blood pressure (mean root-mean-squared error ≤ 6.31 mmHg for diastolic blood pressure and ≤ 8.41 mmHg for systolic blood pressure) over a wide range of hemodynamic changes. CONCLUSION: The proposed pulse pressure estimation method provides accurate estimates in situations with and without significant changes in stroke volume. The proposed method improves upon the currently available systolic blood pressure estimation methods by providing accurate pulse pressure estimates.

Dynamic designing of microstructures by chemical gradient-mediated growth.

Shape is one of the most important determinants of the properties of microstructures. Despite of a recent progress on microfabrication techniques, production of three-dimensional micro-objects are yet to be fully achieved. Nature uses reaction-diffusion process during bottom-up self-assembly to create functional shapes and patterns with high complexity. Here we report a method to produce polymeric microstructures by using a dynamic reaction-diffusion process during top-down photolithography, providing unprecedented control over shape and composition. In radical polymerization, oxygen inhibits reaction, and therefore diffusion of oxygen significantly alters spatial distribution of growth rate. Therefore, growth pathways of the microstructures can be controlled by engineering a concentration gradient of oxygen. Moreover, stepwise control of chemical gradients enables the creation of highly complex microstructures. The ease of use and high controllability of this technology provide new opportunities for microfabrication and for fundamental studies on the relationships between shape and function for the materials.

Microfluidic molding of photonic microparticles with engraved elastomeric membranes.

A microfluidic approach to prepare photonic microparticles by repeated molding of photocurable colloidal suspension is reported. An elastomeric membrane with negative relieves which vertically separates two microfluidic channels is integrated; bottom channel is used for suspension flow, whereas water-filled top channel is used for pneumatic actuation of the membrane. Upon pressurization of the top channel, membrane is deformed to confine the suspension into its negative relieves, which is then polymerized by UV irradiation, making microparticles with mold shape. The microparticles are released from the mold by relieving the pneumatic pressure and flows through the bottom channel. This one cycle of molding, polymerization, and release can be repeatedly performed in microfluidic device of which pneumatic valves are actuated in a programmed manner. The microparticles exhibit structural colors when the suspension contains high concentration of silica nanoparticles; the nanoparticles form regular arrays and the microparticles reflect specific wavelength of light as a photonic crystals. The silica nanoparticles can be selectively removed to make pronounced structural colors. In addition, the microparticles can be further functionalized by embedding magnetic particles in the matrix of the microparticles, enabling the remote control of rotational motion of microparticles.

Ordered packing of emulsion droplets toward the preparation of adjustable photomasks.

Monodisperse emulsion droplets with a high volume fraction form crystalline phases that can potentially serve as adjustable photomasks in photolithography. Such photomasks were prepared using a microfluidic device in which a flow-focusing junction, side channels, and a reservoir were connected in series. Transparent oil droplets were generated in a dye-containing continuous water phase at the flow-focusing junction. The droplets were then concentrated through the selective removal of the continuous phase using the side channels. This process led to the formation of a regular array of droplets in the reservoir with a configuration that depended on the relative height of the reservoir to the droplet diameter. The configurations could be selected among a single-layered hexagonal array, a bilayered square array, and a bilayered hexagonal array. The droplet arrays were used as a photomask to create hexagonal or square arrays of microdots. The transmittance profile of the ultraviolet (UV) light from each droplet was parabolic, which enabled the dot size to be tuned by controlling the UV irradiation time. This mask effect is otherwise difficult to achieve using conventional photomasks. The dot size and array periodicity could be adjusted by the in-situ control of the droplet size at the flow-focusing droplet maker. The combination of droplet size adjustments and the UV irradiation time provided independent control over the dot size and array periodicity to enable the preparation of a series of hexagonal microarrays with a wide spectrum of array parameters using a single microfluidic device.

Magnetoresponsive discoidal photonic crystals toward active color pigments.

Photonic microdisks with a multilayered structure are designed from photocurable suspensions by step-by-step photolithography. In each step of photolithography, either a colloidal photonic crystal or a magnetic-particle-laden layer is stacked over the windows of a photomask. Sequential photolithography enables the creation of multilayered photonic microdisks that have brilliant structural colors that can be switched by an external magnetic field.

Monolithic photonic crystals created by partial coalescence of core-shell particles.

Colloidal crystals and their derivatives have been intensively studied and developed during the past two decades due to their unique photonic band gap properties. However, complex fabrication procedures and low mechanical stability severely limit their practical uses. Here, we report stable photonic structures created by using colloidal building blocks composed of an inorganic core and an organic shell. The core-shell particles are convectively assembled into an opal structure, which is then subjected to thermal annealing. During the heat treatment, the inorganic cores, which are insensitive to heat, retain their regular arrangement in a face-centered cubic lattice, while the organic shells are partially fused with their neighbors; this forms a monolithic structure with high mechanical stability. The interparticle distance and therefore stop band position are precisely controlled by the annealing time; the distance decreases and the stop band blue shifts during the annealing. The composite films can be further treated to give a high contrast in the refractive index. The inorganic cores are selectively removed from the composite by wet etching, thereby providing an organic film containing regular arrays of air cavities. The high refractive index contrast of the porous structure gives rise to pronounced structural colors and high reflectivity at the stop band position.

Controlled pixelation of inverse opaline structures towards reflection-mode displays.

Pixelated inverse opals with red, green, and blue colors were prepared by hybridizing convective assembly of colloidal particles and photolithography techniques. The brilliant structural colors, high mechanical stability, and small feature size of the pixels were simultaneously accomplished, thereby providing color reflectors potentially useful for display devices. Moreover, this hybridized method provides a general means to create multi-colored photonic crystals.

3D hierarchical architectures prepared by single exposure through a highly durable colloidal phase mask.

Three-dimensional hierarchical architectures are fabricated using a simple, cost-effective, durable colloidal phase mask containing a colloidal monolayer embedded in a flexible polydimethylsiloxane (PDMS) membrane. These structures give rise to a photonic bandgap that can be tuned over a wide spectral range from the visible to the near-infrared regions.

Photothermal control of membrane permeability of microcapsules for on-demand release.

We report the use of a simple microfluidic device for producing microcapsules with reversible membrane permeability that can be remotely controlled by application of near-infrared (NIR) light. Water-in-oil-in-water (W/O/W) double-emulsion drops were prepared to serve as templates for the production of mechanically stable microcapsules with a core-shell structure and highly uniform size distribution. A biocompatible ethyl cellulose shell was formed, containing densely packed thermoresponsive poly(N-isopropylacrylamide) (pNIPAAm) particles in which gold nanorods were embedded. Irradiation with a NIR laser resulted in heating of the hydrogel particles due to the photothermal effect of the gold nanorods, which absorb at that wavelength. This localized heating resulted in shrinkage of the particles and formation of macrogaps between them and the matrix of the membrane. Large encapsulated molecules could then pass through these gaps into the surrounding fluid. As the phase transition behavior of pNIPAAm is highly reversible, this light-triggered permeability could be repeatedly switched on and off by removing the laser irradiation for sufficient time to allow the gold nanorods to cool. This reversible and remote control of permeability enabled the programmed release of encapsulants, with the time and period of the open valve state able to be controlled by adjusting the laser exposure. This system thus has the potential for spatiotemporal release of encapsulated drugs.

Droplet microfluidics for producing functional microparticles.

Isotropic microparticles prepared from a suspension that undergoes polymerization have long been used for a variety of applications. Bulk emulsification procedures produce polydisperse emulsion droplets that are transformed into spherical microparticles through chemical or physical consolidation. Recent advances in droplet microfluidics have enabled the production of monodisperse emulsions that yield highly uniform microparticles, albeit only on a drop-by-drop basis. In addition, microfluidic devices have provided a variety of means for particle functionalization through shaping, compartmentalizing, and microstructuring. These functionalized particles have significant potential for practical applications as a new class of colloidal materials. This feature article describes the current state of the art in the microfluidic-based synthesis of monodisperse functional microparticles. The three main sections of this feature article discuss the formation of isotropic microparticles, engineered microparticles, and hybrid microparticles. The complexities of the shape, compartment, and microstructure of these microparticles increase systematically from the isotropic to the hybrid types. Each section discusses the key idea underlying the design of the particles, their functionalities, and their applications. Finally, we outline the current limitations and future perspectives on microfluidic techniques used to produce microparticles.

Bio-inspired nanotadpoles with component-specific functionality.

We report a new class of bio-inspired nanotadpoles (NTPs) with component-specific functionalities. The plasmonic NTPs with a gold-coated head and a reactive ion etching-treated tail showed the tail length dependence of their cellular uptake, enabling the photothermal treatment of cancer cells with high efficacy.

Nanoarchitectures with controllable anisotropic features in structures and properties from simple and robust holographic lithography.

Anisotropic nanostructures with precise orientations or sharp corners display unique properties that may be useful in a variety of applications; however, precise control over the anisotropy of geometric features, using a simple and reproducible large-area fabrication technique, remains a challenge. Here, we report the fabrication of highly uniform polymeric and metallic nanostructure arrays prepared using prism holographic lithography (HL) in such a way that the isotropy that can be readily and continuously tuned. The prism position on the sample stage was laterally translated to vary the relative intensities of the four split beams, thereby tuning the isotropy of the resulting polymer nanostructures through the following shapes: circular nanoholes, elliptical nanoholes, and zigzag-shaped nanoarrays. Corresponding large-area, defect-free anisotropic metallic nanostructures could then be fabricated using an HL-featured porous polymer structure as a milling mask. Removal of the polymer mask left zigzag-shaped metallic nanostructure arrays in which nanogaps separated adjacent sharp edges. These structures displayed two distinct optical properties, depending on the direction along which the excitation beam was polarized (longitudinal and transverse modes) incident on the array. Furthermore, bidirectional anisotropic wetting was observed on the anisotropic polymer nanowall array surface.

Fabrication of three-dimensional nanostructured titania materials by prism holographic lithography and the sol-gel reaction.

We present a simple, easy method for fabricating high-quality titania inverted replicas of 3D holographically featured structures. A combination of single-prism holographic lithography and sol-gel chemistry was used to prepare 3D titania inverse structures with flat and completely open surfaces without the use of additional postprocessing steps, such as reactive ion etching, ion-beam milling, and/or polishing steps. A hydrophobic, stable liquid titania precursor facilitated the complete infiltration of the precursor into the hydrophobic 3D SU-8 polymer template, which produced very uniform high-quality titania inverse structures. Although the degree of film shrinkage during the calcination process was large (∼34%), the optical strength of the 3D titania inverse photonic crystals doubled because of the high-refractive-index contrast. Compared to titania inverse opal structures, the filling fraction (∼27%) of titania materials has been doubled. This is the first work to fabricate titania inverse photonic crystals with a high filling fraction by utilizing prism holographic lithography and the sol-gel chemistry reaction of a stable titania precursor. The X-ray diffraction patterns indicated the presence of a crystalline anatase or rutile phase depending on the calcination temperature.

Durable plasmonic cap arrays on flexible substrate with real-time optical tunability for high-fidelity SERS devices.

Active tunable plasmonic cap arrays were fabricated on a flexible stretchable substrate using a combination of colloidal lithography, lift-up soft lithography, and subsequent electrostatic assembly of gold nanoparticles. The arrangement of the plasmonic caps could be tuned under external strain to deform the substrate in reversible. Real-time variation in the arrangement could be used to tune the optical properties and the electromagnetic field enhancement, thereby a proving a promising mechanism for optimizing the SERS sensitivity.