A Novel Feature Engineering Method Based on Latent Representation Learning for Radiomics: Application in NSCLC Subtype Classification.

Radiomics refers to the high-throughput extraction of quantitative features from medical images, and is widely used to construct machine learning models for the prediction of clinical outcomes, while feature engineering is the most important work in radiomics. However, current feature engineering methods fail to fully and effectively utilize the heterogeneity of features when dealing with different kinds of radiomics features. In this work, latent representation learning is first presented as a novel feature engineering approach to reconstruct a set of latent space features from original shape, intensity and texture features. This proposed method projects features into a subspace called latent space, in which the latent space features are obtained by minimizing a unique hybrid loss function including a clustering-like loss and a reconstruction loss. The former one ensures the separability among each class while the latter one narrows the gap between the original features and latent space features. Experiments were performed on a multi-center non-small cell lung cancer (NSCLC) subtype classification dataset from 8 international open databases. Results showed that compared with four traditional feature engineering methods (baseline, PCA, Lasso and L2,1-norm minimization), latent representation learning could significantly improve the classification performance of various machine learning classifiers on the independent test set (all p<0.001). Further on two additional test sets, latent representation learning also showed a significant improvement in generalization performance. Our research shows that latent representation learning is a more effective feature engineering method, which has the potential to be used as a general technology in a wide range of radiomics researches.

Aptamer-functionalized 2D photonic crystal hydrogels for detection of adenosine.

Aptamer-functionalized two-dimensional photonic crystal (2DPC) hydrogels are reported for the detection of adenosine (AD). As a molecular recognition group, an AD-binding aptamer was covalently attached to 2DPC hydrogels. This aptamer selectively and sensitively binds AD, changing the conformation of the aptamer from a long single-stranded structure (AD-free conformation) to a short hairpin loop structure (AD-bound conformation). The AD-binding-induced changes of aptamer conformation reduced the volume of the 2DPC hydrogels and decreased the interparticle spacing of the 2DPC embedded in the hydrogel network. The particle spacing changes being dependent on AD concentration were determined by measuring 2DPC light diffraction using a simple laser pointer. The 2DPC hydrogel sensor showed a large particle spacing decrease of ~ 110 nm in response to 1 mM AD in phosphate-buffered saline (PBS). The linear range of determination of AD was 0.1 nM to 1 mM and the limit of detection was 0.09 nM. The hydrogel sensor response for real samples was then validated in diluted fetal bovine serum (FBS) and human urine. The average % difference in particle spacing changes measured between diluted FBS and pure PBS was only 3.99%. In diluted human urine, the recoveries for the detection of AD were 95-101% and the relative standard deviations were 4.9-7.8%. The results demonstrate the potential applicability of the hydrogel sensor for real samples. This sensing concept, using the aptamer-functionalized 2DPC hydrogels, allows for a simple, sensitive, selective, and reversible detection of AD. It may enable sensor development for a wide variety of analytes by simply changing the aptamer recognition group.

From colloidal particles to photonic crystals: advances in self-assembly and their emerging applications.

Over the last three decades, photonic crystals (PhCs) have attracted intense interests thanks to their broad potential applications in optics and photonics. Generally, these structures can be fabricated via either "top-down" lithographic or "bottom-up" self-assembly approaches. The self-assembly approaches have attracted particular attention due to their low cost, simple fabrication processes, relative convenience of scaling up, and the ease of creating complex structures with nanometer precision. The self-assembled colloidal crystals (CCs), which are good candidates for PhCs, have offered unprecedented opportunities for photonics, optics, optoelectronics, sensing, energy harvesting, environmental remediation, pigments, and many other applications. The creation of high-quality CCs and their mass fabrication over large areas are the critical limiting factors for real-world applications. This paper reviews the state-of-the-art techniques in the self-assembly of colloidal particles for the fabrication of large-area high-quality CCs and CCs with unique symmetries. The first part of this review summarizes the types of defects commonly encountered in the fabrication process and their effects on the optical properties of the resultant CCs. Next, the mechanisms of the formation of cracks/defects are discussed, and a range of versatile fabrication methods to create large-area crack/defect-free two-dimensional and three-dimensional CCs are described. Meanwhile, we also shed light on both the advantages and limitations of these advanced approaches developed to fabricate high-quality CCs. The self-assembly routes and achievements in the fabrication of CCs with the ability to open a complete photonic bandgap, such as cubic diamond and pyrochlore structure CCs, are discussed as well. Then emerging applications of large-area high-quality CCs and unique photonic structures enabled by the advanced self-assembly methods are illustrated. At the end of this review, we outlook the future approaches in the fabrication of perfect CCs and highlight their novel real-world applications.

Robust Multiscale-Oriented Thermoresponsive Fibrous Hydrogels with Rapid Self-Recovery and Ultrafast Response Underwater.

Hydrogels with ultrafast response to environmental stimuli, possessing robust structural integrity and rapid self-recovery, have been considered as promising platforms for numerous applications, for example, in biomimetic materials and nanomedicine. Inspired by the bundled fibrous structure of actin, we developed a robust and ultrafast thermoresponsive fibrous hydrogel (TFH) by fully utilizing the weak noncovalent bonds and strong covalently cross-linked semiflexible electrospun fibrous nets. The TFH exhibits an ultrafast response (within 10 s), rapid self-recovery rate (74% within 10 s), tunable tensile strength (3-380 kPa), and high toughness (∼1560 J/m2) toward temperature. A multiscale orientation is considered to play a key role in the excellent mechanical properties at the fibrous mesh, fiber, and molecular scales. Furthermore, to take advantage of this TFH adequately, a novel kind of noodle-like hydrogel for thermo-controlled protein sorption based on the TFH is prepared, which exhibits high stability and ultrafast sorption properties. The bioinspired platforms hold promise as artificial skins and "smart" sorption membrane carriers, which provide a unique bioactive environment for tissue engineering and nanomedicine.

Electrically switchable photonic crystals based on liquid-crystal-infiltrated TiO2-inverse opals.

Electrically switchable photonic crystals are demonstrated based on TiO2 inverse opals infiltrated with liquid crystals. Macroporous anatase TiO2 inverse opals are fabricated from polystyrene opal templates through a sandwich vacuum backfilled method and followed by calcination. Upon liquid crystal infiltration, the optical properties of the hybrid organic/inorganic structure are characterized by reflectance measurements of the Bragg peak, the position of which can be switched using an external electric field. The physical mechanism underlying this switchable behavior is the reorientation of the liquid crystal molecules inside the spherical voids by the applied electric field, resulting in a significant change of the refractive index contrast between the liquid crystal and the TiO2 inverse opal. With advantageous features of cost-effective fabrication, easy integration, and electric control, such TiO2 inverse opals infiltrated with liquid crystals could play an important role in future development of active photonic devices.

Poly(propylene fumarate)-based materials: Synthesis, functionalization, properties, device fabrication and biomedical applications.

Poly(propylene fumarate) (PPF) is a biodegradable polymer that has been investigated extensively over the last three decades. It has led many scientists to synthesize and fabricate a variety of PPF-based materials for biomedical applications due to its controllable mechanical properties, tunable degradation and biocompatibility. This review provides a comprehensive overview of the progress made in improving PPF synthesis, resin formulation, crosslinking, device fabrication and post polymerization modification. Further, we highlight the influence of these parameters on biodegradation, biocompatibility, and their use in a number of regenerative medicine applications, especially bone tissue engineering. In particular, the use of 3D printing techniques for the fabrication of PPF-based scaffolds is extensively reviewed. The recent invention of a ring-opening polymerization method affords precise control of PPF molecular mass, molecular mass distribution (ƉM) and viscosity. Low ƉM facilitates time-certain resorption of 3D printed structures. Novel post-polymerization and post-printing functionalization methods have accelerated the expansion of biomedical applications that utilize PPF-based materials. Finally, we shed light on evolving uses of PPF-based materials for orthopedics/bone tissue engineering and other biomedical applications, including its use as a hydrogel for bioprinting.

Responsive Photonic Crystal Carbohydrate Hydrogel Sensor Materials for Selective and Sensitive Lectin Protein Detection.

Lectin proteins, such as the highly toxic lectin protein, ricin, and the immunochemically important lectin, jacalin, play significant roles in many biological functions. It is highly desirable to develop a simple but efficient method to selectively detect lectin proteins. Here we report the development of carbohydrate containing responsive hydrogel sensing materials for the selective detection of lectin proteins. The copolymerization of a vinyl linked carbohydrate monomer with acrylamide and acrylic acid forms a carbohydrate hydrogel that shows specific "multivalent" binding to lectin proteins. The resulting carbohydrate hydrogels are attached to 2-D photonic crystals (PCs) that brightly diffract visible light. This diffraction provides an optical readout that sensitively monitors the hydrogel volume. We utilize lactose, galactose, and mannose containing hydrogels to fabricate a series of 2-D PC sensors that show strong selective binding to the lectin proteins ricin, jacalin, and concanavalin A (Con A). This binding causes a carbohydrate hydrogel shrinkage which significantly shifts the diffraction wavelength. The resulting 2-D PC sensors can selectively detect the lectin proteins ricin, jacalin, and Con A. These unoptimized 2-D PC hydrogel sensors show a limit of detection (LoD) of 7.5 × 10-8 M for ricin, a LoD of 2.3 × 10-7 M for jacalin, and a LoD of 3.8 × 10-8 M for Con A, respectively. This sensor fabrication approach may enable numerous sensors for the selective detection of numerous lectin proteins.

Structural Evolution and Formation Mechanism of the Soft Colloidal Arrays in the Core of PAAm Nanofibers by Electrospun Packing.

Electrospinning provides a facile and versatile method for generating nanofibers from a large variety of starting materials, including polymers, ceramic, composites, and micro-/nanocolloids. In particular, incorporating functional nanoparticles (NPs) with polymeric materials endows the electrospun fibers/sheets with novel or better performance. This work evaluates the spinnability of polyacrylamide (PAAm) solution containing thermoresponsive poly(N-isopropylacrylamide-co-tert-butyl acrylate) microgel nanospheres (PNTs) prepared by colloid electrospinning. In the presence of a suitable weight ratio (1:4) of PAAm and PNTs, the in-fiber arrangements of PNTs-electrospun fibers will evolve into chain-like arrays and beads-on-string structures by confining of PAAm nanofibers, and then the free amide groups of PAAm can bind amide moieties on the surfaces of PNTs, resulting in the assembling of PNTs in the cores of PAAm fibers. The present work serves as a reference in the fabrication of novel thermoresponsive hybrid fibers involving functional nanospheres via electrospun packing. The prepared nanofibers with chain-like and thermoresponsive colloid arrays in the cores are expected to have potential application in various fields.

Photonic crystal protein hydrogel sensor materials enabled by conformationally induced volume phase transition.

Hydrogels that change volume in response to specific molecular stimuli can serve as platforms for sensors, actuators and drug delivery devices. There is great interest in designing intelligent hydrogels for tissue engineering, drug delivery, and microfluidics that utilize protein binding specificities and conformational changes. Protein conformational change induced by ligand binding can cause volume phase transitions (VPTs). Here, we develop a highly selective glucose sensing protein photonic crystal (PC) hydrogel that is fabricated from genetically engineered E. coli glucose/galactose binding protein (GGBP). The resulting 2-D PC-GGBP hydrogel undergoes a VPT in response to glucose. The volume change causes the 2-D PC array particle spacing to decrease, leading to a blue-shifted diffraction which enables our sensors to report on glucose concentrations. This 2-D PC-GGBP responsive hydrogel functions as a selective and sensitive sensor that easily monitors glucose concentrations from ∼0.2 µM to ∼10 mM. This work demonstrates a proof-of-concept for developing responsive, "smart" protein hydrogel materials with VPTs that utilize ligand binding induced protein conformational changes. This innovation may enable the development of other novel chemical sensors and high-throughput screening devices that can monitor protein-drug binding interactions.

A Photonic Crystal Protein Hydrogel Sensor for Candida albicans.

We report two-dimensional (2D) photonic crystal (PC) sensing materials that selectively detect Candida albicans (C. albicans). These sensors utilize Concanavalin A (Con A) protein hydrogels with a 2D PC embedded on the Con A protein hydrogel surface, that multivalently and selectively bind to mannan on the C. albicans cell surface to form crosslinks. The resulting crosslinks shrink the Con A protein hydrogel, reduce the 2D PC particle spacing, and blue-shift the light diffracted from the PC. The diffraction shifts can be visually monitored, measured with a spectrometer, or determined from the Debye diffraction ring diameter. Our unoptimized hydrogel sensor has a detection limit of around 32 CFU/mL for C. albicans. This sensor distinguishes between C. albicans and those microbes devoid of cell-surface mannan such as the gram-negative bacterium E. coli. This sensor provides a proof-of-concept for utilizing recognition between lectins and microbial cell surface carbohydrates to detect microorganisms in aqueous environments.

Two-dimensional photonic crystal chemical and biomolecular sensors.

We review recent progress in the development of two-dimensional (2-D) photonic crystal (PC) materials for chemical and biological sensing applications. Self-assembly methods were developed in our laboratory to fabricate 2-D particle array monolayers on mercury and water surfaces. These hexagonal arrays strongly forward Bragg diffract light to report on their array spacings. By embedding these 2-D arrays onto responsive hydrogel surfaces, 2-D PC sensing materials can be fabricated. The 2-D PC sensors utilize responsive polymer hydrogels that are chemically functionalized to show volume phase transitions in selective response to particular chemical species. Novel hydrogels were also developed in our laboratory by cross-linking proteins while preserving their native structures to maintain their selective binding affinities. The volume phase transitions swell or shrink the hydrogels, which alter their 2-D array spacings, and shift their diffraction wavelengths. These shifts can be visually detected or spectrally measured. These 2-D PC sensing materials have been used for the detection of many analytes, such as pH, surfactants, metal ions, proteins, anionic drugs, and ammonia. We are exploring the use of organogels that use low vapor pressure ionic liquids as their mobile phases for sensing atmospheric analytes.

Two-dimensional photonic crystal sensors for visual detection of lectin concanavalin A.

We fabricated a two-dimensional (2-D) photonic crystal lectin sensing material that utilizes light diffraction from a 2-D colloidal array attached to the surface of a hydrogel that contains mannose carbohydrate groups. Lectin-carbohydrate interactions create hydrogel cross-links that shrink the hydrogel volume and decrease the 2-D particle spacing. This mannose containing 2-D photonic crystal sensor detects Concanavalin A (Con A) through shifts in the 2-D diffraction wavelength. Con A concentrations can be determined by measuring the diffracted wavelength or visually determined from the change in the sensor diffraction color. The concentrations are easily monitored by measuring the 2-D array Debye ring diameter. Our observed detection limit for Con A is 0.02 mg/mL (0.7 µM). The 2-D photonic crystal sensors are completely reversible and can monitor Con A solution concentration changes.

Fabrication of well-ordered binary colloidal crystals with extended size ratios for broadband reflectance.

Binary colloidal crystals (BCCs) possess great potentials in tuning material properties by controlling the size ratio of small to large colloidal spheres (γS/L). In this paper, we present a method for the fabrication of BCCs with much more extended size ratios than those obtained in conventional convective self-assembly method. It is found that γS/L can be extended to 0.376 by adding TEOS sol into the colloidal suspension. The resulting polystyrene/silica (PS/SiO2) BCCs show distinctive reflections, indicating their well-ordered structure. The extended size ratios render more flexibility in engineering the photonic bandgap structures of BCCs and hence provide a better platform for developing a range of applications such as photonics, spintronics, sensing and bioseparation.

2D photonic crystal protein hydrogel coulometer for sensing serum albumin ligand binding.

Bovine and human serum albumin (BSA and HSA) are globular proteins that function as bloodstream carriers of hydrophobes such as fatty acids and drugs. We fabricated novel photonic crystal protein hydrogels by attaching 2D colloidal arrays onto pure BSA and HSA hydrogels. The wavelengths of the diffracted light sensitively report on the protein hydrogel surface area. The binding of charged species to the protein hydrogel gives rise to Donnan potentials that change the hydrogel volume causing shifts in the diffraction. These photonic crystal protein hydrogels act as sensitive Coulometers that monitor the hydrogel charge state. We find multiple high-affinity BSA and HSA binding sites for salicylate, ibuprofen and picosulfate by using these sensors to monitor binding of charged drugs. We demonstrate proof-of-concept for utilizing protein hydrogel sensors to monitor protein-ionic species binding.

Fabrication of large domain crack-free colloidal crystal heterostructures with superposition bandgaps using hydrophobic polystyrene spheres.

An improved convective self-assembly method was developed to fabricate crack-free colloidal crystal heterostructure over a relatively large area. A composite opaline heterostructure composed of polystyrene (PS) colloids was first fabricated. Subsequent calcination of the opaline heterostructure led to the formation of inverse opaline heterostructure composed of SiO(2) or TiO(2). Both opaline and inverse opaline heterostructures demonstrated long-range ordering in a relatively large domain (>100 × 100 µm(2)). Optical reflection measurements of the inverse opaline heterostructures showed dual stop bands as a consequence of the superposition of the stop bands from the individual compositional colloidal crystals (CCs). In addition, the relative position of the two stop bands can be adjusted by varying the size of the colloidal spheres in the original CCs template. Both types of colloidal crystal heterostructures can be used for optical filters, high-efficiency back-reflectors or electrodes in solar cells, differential drug release, and protein patterning.

An improved convective self-assembly method for the fabrication of binary colloidal crystals and inverse structures.

We report an improved convective self-assembly method for the fabrication of highly ordered, crack-free binary colloidal crystals (BCCs) and the associated inverse structures in large domains at length scales of several centimeters. With this method, BCCs can be fabricated in a non-close packed pattern and binary inverse opal films can be obtained over a centimeter scale. The presence of tetraethyl orthosilicate (TEOS) sol in the self-assembly system was found to play a significant role in the resultant structures. The pseudostop band positions are adjustable via varying the number ratio of small to large polystyrene (PS) spheres. At a given TEOS-to-PS ratio, the binary inverse opal film thickness was controllable by varying the colloidal volume fraction with an upper thickness threshold (>16 layers).

Fabrication of TiO2 binary inverse opals without overlayers via the sandwich-vacuum infiltration of precursor.

A sandwich-vacuum method was demonstrated for the fabrication of titania (TiO(2)) binary inverse opals with an open surface. In this method, a moisture-stable TiO(2) precursor was backfilled into the interstitial spaces of polystyrene binary colloidal crystals (PS bCCs), which served as a template. Removal of the template by calcination yielded TiO(2) binary inverse opals with a 3D-ordered macroporous (3DOM) structure. Optical reflectance spectra revealed the existence of a pseudostop band gap in the 3DOM TiO(2) samples. The position of the pseudostop band gap shifted to the low-wavelength region as the number ratio of small over large PS spheres was increased in the template. The sandwich-vacuum method proved to be simple and rapid for the fabrication of TiO(2) binary inverse opals without overlayers in large domains. The 3DOM TiO(2) materials were used as a photocatalyst for the degradation of benzoic acid. Results showed that in comparison to TiO(2) nanoparticles prepared under the same sintering conditions, the 3DOM TiO(2) materials displayed enhanced photocatalytic activity.

Morphological and histological analysis on the in vivo degradation of poly (propylene fumarate)/(calcium sulfate/ß-tricalcium phosphate).

Poly (propylene fumarate)/(Calcium sulfate/ß-tricalcium phosphate) (PPF/(CaSO(4)/ß-TCP)) is a kind of biodegradable composite designed for bone tissue engineering. The in vitro degradation behavior of this composite has been investigated in our previous study. The aim of this study was to investigate the effects of PPF molecular weight and CaSO(4)/ß-TCP molar ratio on the in vivo degradation of PPF/(CaSO(4)/ß-TCP) composite and the bone tissue response to PPF/(CaSO(4)/ß-TCP). Total 36 PPF/(CaSO(4)/ß-TCP) composite samples were implanted into 15.0 mm segmental defects in tibiae of 18 Japanese rabbits, harvested at 2, 4 and 8 weeks after the operation, and analyzed using radiographic and histological analysis to assess the in vivo degradation of the composites as well as tissue response to the implants. The in vivo degradation results show that all the samples maintained their original shape. Tissues penetrated into the pores which formed by the degradation of CaSO(4)/ß-TCP spheres near the surface of the composites. The rate of in vivo degradation and pore forming increased with a decrease in PPF molecular weight and an increase in CaSO(4)/ß-TCP molar ratio. No inflammatory reaction was observed after implantation, and the composites are capable of in situ pore forming. In particular, the pore forming rate can be adjusted by varying the composition of the composites. These results may indicate that PPF/(CaSO(4)/ß-TCP) is a promising osteogenic scaffold for its controllable degradation rate and excellent biocompatibility.

[FTIR study on the synthesis of poly(propylene fumarate) and its copolymer].

Poly(propylene fumarate) (PPF) is one kind of linear biodegradable polyester and the unsaturated double bonds along its main chain can be crosslinked with other olefinic monomers to form three-dimensional networks, and the networks can support tissues. In the present paper, firstly, the intermediate oligomer-bis (2-hydroxypropyl) fumarate (PFP) was synthesized, and then the unsaturated linear polyester PPF was synthesized with the oligomer PFP through melting condensation process. Additionally, on the base of the process, the oligomer bis(2-hydroxypropyl) sebacate (PSP) was synthesized by similar method and then a kind of new copolymer named poly(propylene fumarate-co-propylene sebacate) [P(PF-co-PS)] that comprised bis(2-hydroxypropyl) sebacate segments was synthesized with PFP and PSP by melting condensation. During the synthesis process, the structures of bis(2-hdroxypropyl) fumarate, bis(2-hydroxypropyl) sebacate, PPF and P(PF-co-PS) were characterized by FTIR The results shows that with the polymerization going along, oligomer bis (2-hydroxypropyl) fumarate and bis(2-hydroxypropyl) sebacate converted to PPF or P(PF-co-PS) gradually.

Binary colloidal crystals fabricated with a horizontal deposition method.

We describe the use of a horizontal deposition method to prepare large-area binary colloidal crystals (bCCs). Two different sets of binary polystyrene spheres were employed to demonstrate the validity of this method. By varying the number ratios of small spheres with respect to large spheres, the stoichiometric configuration of the bCCs can be altered. Stable corresponding replica structures of the bCCs were also prepared, and the cross-sectional images of the binary inverse opals were obtained. Optical characterization demonstrated the presence of pseudostop bands, which were in agreement with the compositions of the material. The formation of the bCC by such a simple self-assembly method was attributed to the cooperative effect of interparticle electrostatic interactions and geometrical constrictions. This facile fabrication method further enhances the application potential of the bCCs and their inverse porous replicas with a binary pore system in the fields of photonics, solar cells, separations, catalysis, and biosensing.