Enhancing the processability of poly(benzimidazobenzophenanthroline) through chemical modification

Poly(benzimidazobenzophenanthroline) (BBL), which may be doped into a p- and n-type semiconductor, has been chemically modified to enhance its processability. In its pristine form BBL is processable only in some concentrated acids and nitromethane/Lewis acid solutions. The corrosiveness of these solvents and moisture sensitivity of the solutions severely limits the possibilities for the use of BBL as an electroactive material in organoelectronic devices and limit the possibilities for its post synthetic chemical modification. In this work processable BBL derivatives have been prepared using two different approaches i) preparation of block-copolymers by attachment of water soluble polymers on BBL functional chain ends ii) attaching bulky side groups on one of the monomers and using that as a starting material in the polymerization reaction. Short BBLs of DP 10 or 20 were prepared with functional chain ends and monofunctional poly(ethylene oxide) (PEO) or poly(N-isopropylacrylamide) of several different molecular weights were attached at the chain ends. Elemental analysis showed that the extent of chain end substitution varied quite a lot when PEO was used. It was also shown that thermogravimetric analysis (TGA) was not suitable to determine the fraction of PEO in BBL-PEO block-copolymers. However, the extent of chain end substitution using PNIPAM was evaluated using TGA. BBL-PEOs could be processed into aqueous dispersions at concentrations ≥ 1.5 mg/ml by means of ultrasonication, and these dispersions were proven to be colloidally very stable. The dispersions could be used to spin- or drop cast films. At higher concentrations BBL-PEO dispersions were shown to form gels. The reason for the gelling is the packing of the polymer into nano-wire structures which then aggregate into 3D-network. SEM- and cryo-TEM imaging confirmed the existence of wire-type structures. Wire structures and gelation were also observed for aqueous dispersions of pristine BBL. BBL-PNIPAM block-copolymers were found to be indispersible in water with PNIPAM fractions lower than 35 mass %. However, they gelled upon ultrasonication. With higher PNIPAM fractions the polymers were dispersible and did not form gels in any of the studied concentrations. Dispersibility in water and the colloidal stability of BBL-PEOs and BBL-PNIPAMs was attributed to electrostatic stabilization as the particles showed negative zeta-potentials. Dispersible BBL-PNIPAMs were more stable due the high amount of dissociative groups originating from the partial degradation of the amide moieties during the coupling to BBL. One of the monomers used to prepare BBL, 1,4,5,8-naphthalenetetracarboxylic acid 1,8-monoanhydride, was successfully mono- and dibrominated. The bromine was then used as a functional group and replaced either directly with 2-ethyl-1-hexylamine or substituted with azide and reacted with 1-hexyne. The modified monomers were used in preparation of BBL. BBLs bearing either 2-ethyl-1-hexylamine or 4-butyl-1,2,3-triazole groups were found to be sparingly soluble in dimethylsulphoxide and N-methyl-2-pyrrolidone.Poly(bentsimidatsobentsofenantroliinia) (BBL), joka voidaan lisäaineilla saattaa n- tai p-tyypin puolijohteeksi, muokattiin kemiallisesti sen prosessoitavuuden parantamiseksi. Sellaisenaan BBL on prosessoitavissa ainoastaan joissain vahvoissa hapoissa sekä nitrometaanin ja Lewis-hapon muodostamassa liuoksessa. Näiden liuottimien syövyttävyys ja herkkyys kosteudelle rajoittaa huomattavasti BBL:n käyttöä organoelektronisissa laitteissa. Lisäksi BBL:n kemiallinen muokkaaminen näissä liuottimissa on erittäin hankalaa. Tässä työssä BBL:sta on valmistettu liuosprosessoitavia johdoksia käyttäen kahta lähestymistapaa: i) BBL on syntetisoitu siten, että ketjujen päissä on halutut reaktiiviset ryhmät ja näihin on kiinnitetty lyhyitä vesiliukoisia polymeeriketjuja. ii) Toiseen monomeeriin on kiinnitetty tilaa vieviä sivuryhmiä ja muokattua monomeeriä on käytetty polymeerin valmistamiseen. Lyhyitä BBL-ketjuja, pituudeltaan 10-20 toistuvaa yksikköä, valmistettiin halutuilla funktionaalisilla pääteryhmillä ja näihin ryhmiin liitettiin joko poly(etyleenioksidi)- (PEO) tai poly(n-isopropyyliakryyliamidi) (PNIPAM) -ketju. Alkuaineanalyysi paljasti, että PEO:a liitettäessä pääteryhmien substituutio-aste vaihteli huomattavasti tuotteiden välillä. Tässä yhteydessä tuli myös ilmi, että termogravimetrinen analyysi ei sovi PEO:n määrän arvioimiseen tuotteessa. Toisaalta, PNIPAM:n määrän arvioimiseen lopputuotteessa käytettiin termogravimetriaa. BBL-PEO:t voidaan prosessoida vesidispersioiksi ultraäänellä alle 1.5 mg/ml konsentraatioissa, korkeampien konsentraatioiden johtaessa systeemin geeliytymiseen. Valmistetut dispersiot olivat kolloidisesti stabiileja ja niistä pystyttiin valmistamaan kalvoja spin coating ja drop casting menetelmillä. Geeliytyminen johtuu siitä, että polymeeri pakkautuu vedessä nanosäikeiksi ja säikeet aggregoituvat kolmiulotteiseksi verkkorakenteeksi. Säikeet pystyttiin kuvaamaan elektronimikroskoopeilla (SEM ja cryo-TEM). Myös muokkaamaton BBL muodosti säikeitä vedessä ja muodosti geelejä korkeammissa konsentraatioissa. BBL-PNIPAM polymeerit, joissa PNIPAM:n massaosuus on pienempi kuin 35 %, eivät dispergoidu veteen mutta muodostavat geelejä ultraäänikäsittelyllä. Korkeamman PNIPAM:n massaosuuden tuotteet muodostavat dispersioita mutta eivät geeliydy. Sekä BBL-PEO että BBL-PNIPAM blokkikopolymeerien kyky muodostaa stabiileja dispersioita johtuu elektrostaattisesta stabilisoinnista, mikä näkyi negatiivisina zeta-potentiaaleina. Dispergoituvat BBL-PNIPAM:t muodostavat stabiilempeja dispersioita kuin BBL-PEO:t johtuen dissosioituvien ryhmien suuremmasta määrästä, mikä puolestaan johtuu PNIPAM ketjujen sivuryhmien osittaisesta hajoamisesta liittämisreaktiossa. Yksi BBL:n valmistamiseen käytetyistä monomeereistä, 1,4,5,8-naftaleenitetrakarb-oksyylihappo 1,8-monoanhydridi, saatiin mono- ja dibromattua. Liitettyä bromia käytettiin funktionaalisena ryhmänä ja se korvattiin joko suoraan 2-etyyli-1-heksyyliamiinilla tai vaihdettiin atsidiksi ja reagoitiin 1-heksyynin kanssa. Kummallakin tavalla modifioituja monomeerejä käytettiin BBL:n valmistamiseen. BBL:t joissa oli 2-etyyli-1-heksyyliamiini tai 1-heksyynin kanssa reagoitu atsidi olivat jossain määrin liukoisia dimetyylisulfoksidiin ja N-metyyli-2-pyrrolidoniin

Highly controllable ambient atmosphere spray deposition of water dispersible poly(benzimidazobenzophenanthroline) films

Thin films of water dispersible poly(ethylene oxide) (PEO) functionalized poly(benzimidazobenzophenanthroline) (BBL) polymers have been prepared by a pulse spray technique on a spinning substrate in ambient atmosphere. The deposition method is advantageous for generating ultra-thin films of nanometer thicknesses. A single spray pulse was found in a reproducible manner to generate a layer of ca. 2 nm thickness. The PEO-chain length in the BBL functionalization had an essential influence on the building mechanism of the films. The polymers functionalized by short PEO chains induced the formation of very smooth films while longer PEO chains induced rough films and notable nanostructuration. The BBL-PEO film deposited using spray pulse deposition was found to be electro- and photoactive. The electron transfer processes observed are slightly different from earlier reported results for similar polymers, which is probably due to the very thin film. The films exhibited photocurrent generation when transformed into conducting form.Peer reviewe

Microfluidic preparation and optimization of sorafenib-loaded poly(ethylene glycol-block-caprolactone) nanoparticles for cancer therapy applications

The use of amphiphilic block copolymers to generate colloidal delivery systems for hydrophobic drugs has been the subject of extensive research, with several formulations reaching the clinical development stages. However, to generate particles of uniform size and morphology, with high encapsulation efficiency, yield and batch-to-batch reproducibility remains a challenge, and various microfluidic technologies have been explored to tackle these issues. Herein, we report the development and optimization of poly(ethylene glycol)-block-(ε-caprolactone) (PEG-b-PCL) nanoparticles for intravenous delivery of a model drug, sorafenib. We developed and optimized a glass capillary microfluidic nanoprecipitation process and studied systematically the effects of formulation and process parameters, including different purification techniques, on product quality and batch-to-batch variation. The optimized formulation delivered particles with a spherical morphology, small particle size (dH < 80 nm), uniform size distribution (PDI < 0.2), and high drug loading degree (16 %) at 54 % encapsulation efficiency. Furthermore, the stability and in vitro drug release were evaluated, showing that sorafenib was released from the NPs in a sustained manner over several days. Overall, the study demonstrates a microfluidic approach to produce sorafenib-loaded PEG-b-PCL NPs and provides important insight into the effects of nanoprecipitation parameters and downstream processing on product quality.Peer reviewe

Molecular crowding facilitates assembly of spidroin-like proteins through phase separation

Gaining insights into the processes that transform dispersed biopolymers into well-ordered structures, such as soluble spidroin-proteins to spider silk threads, is essential for attempts to understand their biological function and to mimic their unique properties. One of these processes is liquid-liquid phase separation, which can act as an intermediate step for molecular assembly. We have shown that a self-coacervation step that occurs at a very high protein concentration (> 200 gl(-1)) is crucial for the fiber assembly of an engineered triblock silk-like molecule. In this study, we demonstrate that the addition of a crowding agent lowers the concentration at which coacervation occurs by almost two orders of magnitude. Coacervates induced by addition of a crowding agent are functional in terms of fiber formation, and the crowding agent appears to affect the process solely by increasing the effective concentration of the protein. Furthermore, induction at lower concentrations allows us to study the thermodynamics of the system, which provides insights into the coacervation mechanism. We suggest that this approach will be valuable for studies of biological coacervating systems in general.Peer reviewe

All-in-one microfluidic assembly of insulin-loaded pH-responsive nano-in-microparticles for oral insulin delivery

Here, a continuous two-step glass-capillary microfluidic technique to produce a multistage oral delivery system is reported. Insulin is successfully encapsulated into liposomes, which are coated with chitosan to improve their mucoadhesion. The encapsulation in an enteric polymer offers protection from the harsh gastric conditions. Insulin permeability is enhanced across an intestinal monolayer.Peer reviewe

Melt-electrospinning as a method to improve the dissolution and physical stability of a poorly water-soluble drug

The present study introduces a modified melt-electrospinning (MES) method for fabricating the melt-electrospun fibers (MSFs) of a poorly water-soluble drug and carrier polymer. The MES of poorly water-soluble model drug indomethacin (IND) and hydrophilic carrier polymer, Soluplus (R) (SOL) were prepared at a 1:3 drug-polymer weight ratio. Water was used as an external plasticizer to regulate a MES processing temperature and to improve fiber formation. The fiber size, surface morphology, physical solid state, drug-polymer (carrier) interactions, thermal and chemical stability and dissolution behavior of MSFs were investigated. Solid state nuclear magnetic resonance spectroscopy (NMR) was used to measure T1(H-1), and the domain size of IND in MSFs (25-100 nm) was calculated from these results. Solid-state and thermal analysis confirmed the presence of amorphous solid dispersions of IND and SOL. IND was found to be chemically stable during an entire MES process. Only small drug content variability of different MSF batches was detected with high performace liquid chromatography (HPLC). Given findings were verified with the liquid NMR spectroscopy. The dissolution of MSFs was significantly faster than that of physical mixtures (PMs) or pure drug. The enhanced dissolution of MSFs was caused by high surface area, amorphous state of the drug and solubilizing properties of the carrier polymer (SOL).Peer reviewe

Discrepancies between Radiology Specialists and Residents in Fracture Detection from Musculoskeletal Radiographs

(1) Background: The aim of this study was to compare the competence in appendicular trauma radiograph image interpretation between radiology specialists and residents. (2) Methods: In this multicenter retrospective cohort study, we collected radiology reports from radiology specialists (N = 506) and residents (N = 500) during 2018–2021. As a reference standard, we used the consensus of two subspecialty-level musculoskeletal (MSK) radiologists, who reviewed all original reports. (3) Results: A total of 1006 radiograph reports were reviewed by the two subspecialty-level MSK radiologists. Out of the 1006 radiographs, 41% were abnormal. In total, 67 radiographic findings were missed (6.7%) and 31 findings were overcalled (3.1%) in the original reports. Sensitivity, specificity, positive predictive value, and negative predictive value were 0.86, 0.92, 0.91 and 0.88 respectively. There were no statistically significant differences between radiology specialists’ and residents’ competence in interpretation (p = 0.44). However, radiology specialists reported more subtle cases than residents did (p = 0.04). There were no statistically significant differences between errors made in the morning, evening, or night shifts (p = 0.57). (4) Conclusions: This study found a lack of major discrepancies between radiology specialists and residents in radiograph interpretation, although there were differences between MSK regions and in subtle or obvious radiographic findings. In addition, missed findings found in this study often affected patient treatment. Finally, there are MSK regions where the sensitivity or specificity is below 90%, and these should raise concerns and highlight the need for double reading and should be taken into consideration in radiology education.Peer reviewe

Deep learning accurately classifies elbow joint effusion in adult and pediatric radiographs

Joint effusion due to elbow fractures are common among adults and children. Radiography is the most commonly used imaging procedure to diagnose elbow injuries. The purpose of the study was to investigate the diagnostic accuracy of deep convolutional neural network algorithms in joint effusion classification in pediatric and adult elbow radiographs. This retrospective study consisted of a total of 4423 radiographs in a 3-year period from 2017 to 2020. Data was randomly separated into training (n = 2672), validation (n = 892) and test set (n = 859). Two models using VGG16 as the base architecture were trained with either only lateral projection or with four projections (AP, LAT and Obliques). Three radiologists evaluated joint effusion separately on the test set. Accuracy, precision, recall, specificity, F1 measure, Cohen's kappa, and two-sided 95% confidence intervals were calculated. Mean patient age was 34.4 years (1-98) and 47% were male patients. Trained deep learning framework showed an AUC of 0.951 (95% CI 0.946-0.955) and 0.906 (95% CI 0.89-0.91) for the lateral and four projection elbow joint images in the test set, respectively. Adult and pediatric patient groups separately showed an AUC of 0.966 and 0.924, respectively. Radiologists showed an average accuracy, sensitivity, specificity, precision, F1 score, and AUC of 92.8%, 91.7%, 93.6%, 91.07%, 91.4%, and 92.6%. There were no statistically significant differences between AUC's of the deep learning model and the radiologists (p value > 0.05). The model on the lateral dataset resulted in higher AUC compared to the model with four projection datasets. Using deep learning it is possible to achieve expert level diagnostic accuracy in elbow joint effusion classification in pediatric and adult radiographs. Deep learning used in this study can classify joint effusion in radiographs and can be used in image interpretation as an aid for radiologists

A molecular-based identification resource for the arthropods of Finland

Publisher Copyright: © 2021 The Authors. Molecular Ecology Resources published by John Wiley & Sons Ltd.To associate specimens identified by molecular characters to other biological knowledge, we need reference sequences annotated by Linnaean taxonomy. In this study, we (1) report the creation of a comprehensive reference library of DNA barcodes for the arthropods of an entire country (Finland), (2) publish this library, and (3) deliver a new identification tool for insects and spiders, as based on this resource. The reference library contains mtDNA COI barcodes for 11,275 (43%) of 26,437 arthropod species known from Finland, including 10,811 (45%) of 23,956 insect species. To quantify the improvement in identification accuracy enabled by the current reference library, we ran 1000 Finnish insect and spider species through the Barcode of Life Data system (BOLD) identification engine. Of these, 91% were correctly assigned to a unique species when compared to the new reference library alone, 85% were correctly identified when compared to BOLD with the new material included, and 75% with the new material excluded. To capitalize on this resource, we used the new reference material to train a probabilistic taxonomic assignment tool, FinPROTAX, scoring high success. For the full-length barcode region, the accuracy of taxonomic assignments at the level of classes, orders, families, subfamilies, tribes, genera, and species reached 99.9%, 99.9%, 99.8%, 99.7%, 99.4%, 96.8%, and 88.5%, respectively. The FinBOL arthropod reference library and FinPROTAX are available through the Finnish Biodiversity Information Facility (www.laji.fi) at https://laji.fi/en/theme/protax. Overall, the FinBOL investment represents a massive capacity-transfer from the taxonomic community of Finland to all sectors of society.Peer reviewe

Time-dependent self-association of spruce galactoglucomannans depends on pH and mechanical shearing

The demand for naturally derived, functional and cost-effective raw materials for various food applications is escalating. Spruce wood is a sustainable and abundant, but underutilized source of novel hydrocolloids-galactoglucomannans (GGM). Pressurized-hot water extracted GGM with an intermediate molar mass are hypothesized to form colloidal solutions. To design superior quality products from GGM, an understanding of their colloidal stability and their potential effect in multiphasic systems is required. The present study addresses the functionality of GGM by characterizing their properties in a bi-phasic system, and for the first time, their time-dependent colloidal stability at different extrinsic conditions- pH, ionic strength and after the application of high-intensity mechanical shearing. Amongst the conditions studied, the colloidal stability of aqueous GGM solution was highly pH dependent. The results showed that an intermediate molar mass polysaccharide like GGM formed inter-/intra molecular assemblies, which grew over time, depending on the composition and processing of the aqueous medium. The molecular dispersion of GGM and their dynamic behavior was also compared to solutions of known food hydrocolloids-gum Arabic and hydroxypropylmethyl cellulose. The observed solution properties explain the hydmcolloid functionality of GGM and contribute to design of colloidal polysaccharide systems in food application.Peer reviewe