High Negative Fixed Charge Density Research Articles

Drug delivery carriers can alter cartilage biomechanics

Development of effective osteoarthritis (OA) therapeutics is challenged by difficulties in delivering drug molecules into articular cartilage, owing to the dense nature of cartilage extracellular matrix (ECM) and the fast clearance of drug molecules in the synovial joint ( 1 Bajpayee A.G. Grodzinsky A.J. Cartilage-targeting drug delivery: can electrostatic interactions help?. Nat. Rev. Rheumatol. 2017; 13: 183-193https://doi.org/10.1038/nrrheum.2016.210 Crossref PubMed Scopus (120) Google Scholar ). Cartilage ECM is characterized by a high negative fixed charge density, endowed by the proteoglycan, aggrecan, and its sulfated glycosaminoglycan (sGAG) side chains ( 2 Han L. Grodzinsky A.J. Ortiz C. Nanomechanics of the cartilage extracellular matrix. Annu. Rev. Mater. Res. 2011; 41: 133-168https://doi.org/10.1146/annurev-matsci-062910-100431 Crossref PubMed Scopus (135) Google Scholar ). Building on this knowledge, researchers have developed various cationic drug delivery carriers to promote drug penetration deep into cartilage, targeting chondrocytes throughout the whole tissue depth. A few examples include peptides ( 3 Vedadghavami A. Wagner E.K. Bajpayee A.G. et al. Cartilage penetrating cationic peptide carriers for applications in drug delivery to avascular negatively charged tissues. Acta Biomater. 2019; 93: 258-269https://doi.org/10.1016/j.actbio.2018.12.004 Crossref PubMed Scopus (41) Google Scholar ), proteins ( 4 DiDomenico C.D. Bonassar L.J. The effect of charge and mechanical loading on antibody diffusion through the articular surface of cartilage. J. Biomech. Eng. 2018; 141: 014502https://doi.org/10.1115/1.4041768 Crossref Scopus (4) Google Scholar ), synthetic polymers ( 5 Geiger B.C. Wang S. Hammond P.T. et al. Cartilage-penetrating nanocarriers improve delivery and efficacy of growth factor treatment of osteoarthritis. Sci. Transl. Med. 2018; 10: eaat8800https://doi.org/10.1126/scitranslmed.aat8800 Crossref PubMed Scopus (121) Google Scholar ), and nanoparticles ( 6 Yan H. Duan X. Pham C.T.N. et al. Suppression of NF-κB activity via nanoparticle-based siRNA delivery alters early cartilage responses to injury. Proc. Natl. Acad. Sci. USA. 2016; 113: E6199-E6208https://doi.org/10.1073/pnas.1608245113 Crossref PubMed Scopus (79) Google Scholar ). Effects of polycationic drug carriers on the electromechanical and swelling properties of cartilageWarren et al.Biophysical JournalJune 27, 2022In BriefCationic nanocarriers offer a promising solution to challenges in delivering drugs to negatively charged connective tissues, such as to articular cartilage for the treatment of osteoarthritis (OA). However, little is known about the effects that cationic macromolecules may have on the mechanical properties of cartilage at high interstitial concentrations. We utilized arginine-rich cationic peptide carriers (CPCs) with varying net charge (from +8 to +20) to investigate the biophysical mechanisms of nanocarrier-induced alterations to cartilage biomechanical properties. Full-Text PDF

Tube‐type plasma‐enhanced atomic layer deposition of aluminum oxide: Enabling record lab performance for the industry with demonstrated cell efficiencies >24%

AbstractIn this work, single‐side aluminum oxide (Al2O3) deposition enabled by a new tube‐type industrial plasma‐assisted atomic layer deposition (PEALD) technique is presented to meet the increasingly stringent requirements for high‐efficiency solar cell mass production. Extremely low emitter saturation current densities, J0e, down to 15 fA/cm2 are achieved on an industrial textured boron emitter with a sheet resistance of 104 Ω/sq, passivated by PEALD Al2O3/PECVD SiNx stack after firing. An implied open‐circuit voltage of up to 721 mV is obtained on symmetrical lifetime samples. The underlying passivation mechanisms of this new tube‐type PEALD Al2O3 are investigated by contactless corona‐voltage measurements. The results indicate that the superior passivation is mainly attributed to a low interface defect density down to 1.1 × 1011 cm−2 eV−1 and a high negative fixed charge density up to 4.5 × 1012 cm−2. Simulations show that the obtained J0e is close to its intrinsic limit. Lastly, the developed tube‐type PEALD Al2O3 is applied to industrial TOPCon solar cells achieving an average cell efficiency above 24% and a maximum Voc of 707 mV. This work shows that the record level of surface passivation available from lab‐scale PEALD reactors is now available in a flexible high‐throughput industrial PEALD platform, which opens a new route for mass production of high‐efficiency industrial TOPCon solar cells with a lean process at low costs.

Effect of the thickness of amorphous silicon carbide interlayer on the passivation of c-Ge surface by aluminium oxide films

Surface passivation is of paramount importance in photovoltaic devices based on high-quality crystalline absorbers such as crystalline germanium (c-Ge). In this work, we report on the surface passivation of p-type c-Ge by an amorphous silicon carbide/aluminium oxide film stack (a-SiCx/Al2O3). In particular, we focus on the impact of the thin (0, 1, 2, and 4 nm) a-SiCx interlayer which is used to provide chemical passivation while the Al2O3 is responsible for the field-effect passivation due to its high negative fixed charge density. The measured effective surface recombination velocity (Seff) values show that the introduction of the a-SiCx interlayer improves surface passivation, but the thinner the a-SiCx film the better. High frequency capacitance-voltage characterization leads to the determination of the fixed charge density (Qf) which indicates that the a-SiCx is shielding the negative charge located at the first nanometers of the Al2O3 film, as suggested by chemical characterization of the interface. As a consequence, the best result is Seff = 18 cm/s for the case of 1 nm of a-SiCx.

Excellent surface passivation of germanium by a-Si:H/Al2O3 stacks

Surface passivation of germanium is vital for optimal performance of Ge based optoelectronic devices especially considering their rapidly increasing surface-to-volume ratios. In this work, we have investigated the surface passivation of Ge by a stack consisting of a thin layer of hydrogenated amorphous silicon (a-Si:H) and an aluminum oxide (Al2O3) capping layer. Plasma-enhanced chemical vapor deposition was used to deposit the a-Si:H (0–10 nm), while thermal and plasma-enhanced atomic layer deposition (ALD) were employed for the Al2O3 films (0–22 nm). Transient photoconductance decay measurements revealed a recombination velocity as low as 2.7 cm s−1 for an a-Si:H layer as thin as 1.8 nm and an Al2O3 film of only ∼6 nm. In this state-of-the-art passivation scheme, the plasma-enhanced ALD process for the Al2O3 capping layer proved superior to the thermal ALD process since it resulted in an exceptionally high negative fixed charge density (Qf ∼ 1013 cm−2), which proved a key factor for the low surface recombination velocity. Transmission electron microscopy and energy x-ray dispersion revealed that a thin SiOx layer (∼1.4 nm) forms between a-Si:H and Al2O3 during the ALD process, which is thought to be the origin of this high negative fixed charge density. This passivation stack is regarded as highly interesting for applications such as solar cells, nanolasers, and nano-LEDs based on p-type Ge.

Engineering aluminum oxide/polysilicon hole selective passivated contacts for high efficiency solar cells

Tunnel layer passivated contact technology is already highly efficient in case of selective electron extraction but not as efficient in case of selective hole extraction. Thus far, SiOx/p+-poly-Si contacts have resulted only in efficiencies above ~20.1% for rear-side deployed hole selective contacts. We investigate if hole extraction selectivity can be further improved by substituting the ‘conventionally’ used SiOx tunnel layer exhibiting moderate or even high positive fixed charge density by AlOx tunnel layers, exhibiting high negative fixed charge density. The merits of using atomic layer deposited ultrathin AlOx tunnel layers are investigated and compared with wet chemically formed SiOx tunnel layers to form AlOx/p+-poly-Si and SiOx/p+-poly-Si hole selective passivated contacts respectively. The AlOx thickness (0.13–2 nm) and its thermal budget including annealing time, temperature and ambient were varied. The quality of the resulting AlOx/p+-poly-Si passivated contacts was determined by measuring the recombination current density (Jc) and the effective contact resistivity (ρc). Finally, using the measured values of Jc and ρc, we predict the efficiency potential and selectivity of the passivated contact using Brendel's model. We show that for 425 °C annealed AlOx samples prior to poly-Si capping, there is an improvement in passivation quality due to the high negative AlOx interface charge, which forms only for “thick” tunnel layers (≥1.5 nm). However, after high-temperature poly-Si capping, enhanced boron in-diffusion and charge compensation are degrading the overall passivation quality of “thick” AlOx/p+-poly-Si passivated contacts. The best AlOx/p+-poly-Si passivated contacts use ultra-thin AlOx tunnel layers (efficiency potential of 26.9%), which is only marginally better than the SiOx reference samples, but still improves hole selectivity.

Characterization of Intra-Cartilage Transport Properties of Cationic Peptide Carriers.

Several negatively charged tissues in the body, like cartilage, present a barrier to the targeted drug delivery due to their high density of negatively charged aggrecans and, therefore, require improved targeting methods to increase their therapeutic response. Because cartilage has a high negative fixed charge density, drugs can be modified with positively charged drug carriers to take advantage of electrostatic interactions, allowing for enhanced intra-cartilage drug transport. Studying the transport of drug carriers is, therefore, crucial towards predicting the efficacy of drugs in inducing a biological response. We show the design of three experiments which can quantify the equilibrium uptake, depth of penetration and non-equilibrium diffusion rate of cationic peptide carriers in cartilage explants. Equilibrium uptake experiments provide a measure of the solute concentration within the cartilage compared to its surrounding bath, which is useful for predicting the potential of a drug carrier in enhancing therapeutic concentration of drugs in cartilage. Depth of penetration studies using confocal microscopy allow for the visual representation of 1D solute diffusion from the superficial to deep zone of cartilage, which is important for assessing whether solutes reach their matrix and cellular target sites. Non-equilibrium diffusion rate studies using a custom-designed transport chamber enables the measurement of the strength of binding interactions with the tissue matrix by characterizing the diffusion rates of fluorescently labeled solutes across the tissue; this is beneficial for designing carriers of optimal binding strength with cartilage. Together, the results obtained from the three transport experiments provide a guideline for designing optimally charged drug carriers which take advantage of weak and reversible charge interactions for drug delivery applications. These experimental methods can also be applied to evaluate the transport of drugs and drug-drug carrier conjugates. Further, these methods can be adapted for the use in targeting other negatively charged tissues such as meniscus, cornea and the vitreous humor.

Avidin grafted dextran nanostructure enables a month-long intra-discal retention

Low back pain is often the direct result of degeneration of the intervertebral disc. A wide range of therapeutics including anti-catabolic, pro-anabolic factors and chemo-attractants that can stimulate resident cells and recruit endogenous progenitors are under consideration. The avascular nature and the dense matrix of this tissue make it challenging for systemically administered drugs to reach their target cells inside the nucleus pulposus (NP), the central gelatinous region of the intervertebral disc (IVD). Therefore, local intra-discal injection of therapeutic drugs directly into the NP is a clinically relevant delivery approach, however, suffers from rapid and wide diffusion outside the injection site resulting in short lived benefits while causing systemic toxicity. NP has a high negative fixed charge density due to the presence of negatively charged aggrecan glycosaminoglycans that provide swelling pressures, compressive stiffness and hydration to the tissue. This negative fixed charge density can also be used for enhancing intra-NP residence time of therapeutic drugs. Here we design positively charged Avidin grafted branched Dextran nanostructures that utilize long-range binding effects of electrostatic interactions to bind with the intra-NP negatively charged groups. The binding is strong enough to enable a month-long retention of cationic nanostructures within the NP following intra-discal administration, yet weak and reversible to allow movement to reach cells dispersed throughout the tissue. The branched carrier has multiple sites for drug conjugation and can reduce the need for multiple injections of high drug doses and minimize associated side-effects, paving the way for effective clinical translation of potential therapeutics for treatment of low back pain and disc degeneration.

Overcoming negatively charged tissue barriers: Drug delivery using cationic peptides and proteins.

Negatively charged tissues are ubiquitous in the human body and are associated with a number of common diseases yet remain an outstanding challenge for targeted drug delivery. While the anionic proteoglycans are critical for tissue structure and function, they make tissue matrix dense, conferring a high negative fixed charge density (FCD) that makes drug penetration through the tissue deep zones and drug delivery to resident cells extremely challenging. The high negative FCD of these tissues is now being utilized by taking advantage of electrostatic interactions to create positively charged multi-stage delivery methods that can sequentially penetrate through the full thickness of tissues, create a drug depot and target cells. After decades of work on attempting delivery using strong binding interactions, significant advances have recently been made using weak and reversible electrostatic interactions, a characteristic now considered essential to drug penetration and retention in negatively charged tissues. Here we discuss these advances using examples of negatively charged tissues (cartilage, meniscus, tendons and ligaments, nucleus pulposus, vitreous of eye, mucin, skin), and delve into how each of their structures, tissue matrix compositions and high negative FCDs create barriers to drug entry and explore how charge interactions are being used to overcome these barriers. We review work on tissue targeting cationic peptide and protein-based drug delivery, compare and contrast drug delivery designs, and also present examples of technologies that are entering clinical trials. We also present strategies on further enhancing drug retention within diseased tissues of lower FCD by using synergistic effects of short-range binding interactions like hydrophobic and H-bonds that stabilize long-range charge interactions. As electrostatic interactions are incorporated into design of drug delivery materials and used as a strategy to create properties that are reversible, tunable and dynamic, bio-electroceuticals are becoming an exciting new direction of research and clinical work.

Multi-arm Avidin nano-construct for intra-cartilage delivery of small molecule drugs

Targeted drug delivery to joint tissues like cartilage remains a challenge that has prevented clinical translation of promising osteoarthritis (OA) drugs. Local intra-articular (IA) injections of drugs suffer from rapid clearance from the joint space and slow diffusive transport through the dense, avascular cartilage matrix comprised of negatively charged glycosaminoglycans (GAGs). Here we apply drug carriers that leverage electrostatic interactions with the tissue's high negative fixed charge density (FCD) for delivering small molecule drugs to cartilage cell and matrix sites. We demonstrate that a multi-arm cationic nano-construct of Avidin (mAv) with 28 sites for covalent drug conjugation can rapidly penetrate through the full thickness of cartilage in high concentration and have long intra-cartilage residence time in both healthy and arthritic cartilage via weak-reversible binding with negatively charged aggrecans. mAv's intra-cartilage mean uptake was found to be 112× and 33× the equilibration bath concentration in healthy and arthritic (50% GAG depleted) cartilage, respectively. mAv was conjugated with Dexamethasone (mAv-Dex), a broad-spectrum glucocorticoid, using a combination of hydrolysable ester linkers derived from succinic anhydride (SA), 3,3-dimethylglutaric anhydride (GA) and phthalic anhydride (PA) in 2:1:1 M ratio that enabled 50% drug release within 38.5 h followed by sustained release in therapeutic doses over 2 weeks. A single 10 μM low dose of controlled release mAv-Dex (2:1:1) effectively suppressed IL-1α-induced GAG loss, cell death and inflammatory response significantly better than unmodified Dex over 2 weeks in cartilage explant culture models of OA. With this multi-arm design, <1 μM Avidin was needed – a concentration which has been shown to be safe, preventing further GAG loss and cytotoxicity. A charge-based cartilage homing drug delivery platform like this can elicit disease modifying effects as well as facilitate long-term symptomatic pain and inflammation relief by enhancing tissue specificity and prolonging intra-cartilage residence time of OA drugs. This nano-construct thus has high translational potential for enabling intra-cartilage delivery of a broad array of small molecule OA drugs and their combinations to chondrocytes, enabling OA treatment with a single injection of low drug doses and eliminating toxicity issues associated with multiple high dose injections.

Cartilage penetrating cationic peptide carriers for applications in drug delivery to avascular negatively charged tissues

Drug delivery to avascular, negatively charged tissues like cartilage remains a challenge. The constant turnover of synovial fluid results in short residence time of administered drugs in the joint space and the dense negatively charged matrix of cartilage hinders their diffusive transport. Drugs are, therefore, unable to reach their cell and matrix targets in sufficient doses, and fail to elicit relevant biological response, which has led to unsuccessful clinical trials. The high negative fixed charge density (FCD) of cartilage, however, can be used to convert cartilage from a barrier to drug entry into a depot by making drugs positively charged. Here we design cartilage penetrating and binding cationic peptide carriers (CPCs) with varying net charge, spatial distribution and hydrophobicity to deliver large-sized therapeutics and investigate their electro-diffusive transport in healthy and arthritic cartilage. We showed that CPC uptake increased with increasing net charge up to +14 but dropped as charge increased further due to stronger binding interactions that hindered CPC penetrability and uptake showing that weak-reversible binding is key to enable their penetration through full tissue thickness. Even after 90% GAG depletion, while CPC +14 uptake reduced by over 50% but still had a significantly high value of 148× showing that intra-tissue long-range charge-based binding is further stabilized by short-range H-bond and hydrophobic interactions. The work presents an approach for rational design of cationic carriers based on tissue FCD and properties of macromolecules to be delivered. These design rules can be extended to drug delivery for other avascular, negatively charged tissues. Statement of SignificanceOsteoarthritis (OA) remains an untreatable disease partly due to short joint residence time of drugs and a lack of delivery methods that can effectively target the dense, avascular, highly negatively charged cartilage tissue. In this study, we designed cartilage penetrating and binding cationic peptide carriers (CPCs) that, due to their optimal charge provide adequate electrical driving force to rapidly transport OA drugs into cartilage and reach their cell and matrix targets in therapeutic doses before drugs exit the joint space. This way cartilage is converted from being a barrier to drug entry into a drug depot that can provide sustained drug release for several weeks. This study also investigates synergistic effects of short-range H-bond and hydrophobic interactions in combination with long-range electrostatic interactions on intra-cartilage solute transport. The work provides rules for rational design of cartilage penetrating charge-based carriers depending on the net charge of tissue (normal versus arthritic), macromolecule to be delivered and whether the application is in drug delivery or tissue imaging.

Structure-activity relationship study of hypoxia-activated prodrugs for proteoglycan-targeted chemotherapy in chondrosarcoma

Due to an abundant chondrogenic, poorly vascularized and particularly hypoxic extracellular matrix, chondrosarcoma, a malignant cartilaginous tumour, is chemo- and radio-resistant. Surgical resection with wide margins remains the mainstay of treatment. To address the lack of therapy, our strategy aims to increase anticancer drugs targeting and delivery in the tumour, by leveraging specific chondrosarcoma hallmarks: an extensive cartilaginous extracellular matrix, namely the high negative fixed charge density and severe chronic hypoxia. A dual targeted therapy for chondrosarcoma was investigated by conjugation of a hypoxia-activated prodrug (HAP) to quaternary ammonium (QA) functions which exhibit a high affinity for polyanionic sites of proteoglycans (PGs), the major components of the chondrosarcoma extracellular matrix. Based on preclinical results, an imidazole prodrug, ICF05016, was identified and provided the basis for a lead optimization study. A series of 27 QA-phosphoramide mustard conjugates, differing by the type of QA function and the length of the alkyl linker, was yielded by a common multi-step sequence involving phosphorylation of a key 2-nitroimidazole alcohol. Then, a screening was realized by surface plasmon resonance technology to assess biomolecular interactions between QA derivatives and aggrecan, the most abundant PG in chondrosarcoma. Results revealed that affinity depends more on the type of QA function, than on the linker length. Moreover, the presence of a benzyl group enhanced affinity to aggrecan. Twelve compounds were shortlisted and evaluated for antiproliferative activity (i.e., growth inhibiting concentration 50), under normoxic and hypoxic conditions using the human extraskeletal myeloid chondrosarcoma cell line (HEMC-SS). For all prodrugs, hypoxic selectivity was maintained and even increased, compared with the lead. From this study, compound 31f emerged as the most effective PG-targeted HAPs with a dissociation constant of 2.10 μM in the SPR experiment, a hypoxia cytotoxicity ratio of 24 and an efficient reductive cleavage under chemical and enzymatic conditions.

Influence of aluminum workfunction and capping dielectric thickness on the performance of local back surface field solar cell using numerical simulation

High efficiency partial rear contact solar cells forms a Metal-Insulator-Semiconductor (MIS) stack in the rear side. Aluminum is used as a local back surface field (localized heavily doped pregion) and a hole contact. The workfunction difference between the aluminum contact and the c-Si(p) causes inversion in the silicon surface of the MIS structure. The surface inversion affects the quality of passivation and hence, the performance of the solar cell which requires further understanding. In this work, we have analysed the influence of aluminum on surface passivation in two passivation stacks namely (i)AlOx/SiNx and (ii) SiOx/SiNx using Sentaurus TCAD simulation.Our simulation result shows that in case of positive dielectric stack (SiOx/SiNx), aluminum workfunction enhances the passivation (effective surface recombination velocity <15cm/s) for the injection condition of 2×1013cm-3 which is common at the rear side of AlLBSF solar cell. But, in negative dielectric stack (AlOx/SiNx), aluminum workfunction influence is negligible since it is surpassed by high negative fixed charge density. In addition, we have varied the capping layer (SiNx) thickness in the dielectric stack to alter the aluminum influence on the crystalline silicon surface. It shows up to 1.0% absolute improvement in the efficiency for reduced SiNx thickness in the SiOx/SiNx stack for the fixed charge density of 2×1011cm-2, interface trap density of 5×1011cm-2, assumed electron and hole capture cross section of 10-14cm2 and 4×10-16cm2 respectively. This is solely attributed to the aluminum workfunction influence on the rear passivation.

Improved Silicon Surface Passivation of APCVD Al2O3 by Rapid Thermal Annealing

Short-duration post-deposition thermal treatments at temperatures above those normally used for annealing activation have the potential to further improve the already excellent passivation of crystalline silicon (c-Si) achieved by Al2O3, but have so far received little attention. In this work we investigate the influence of rapid thermal annealing (RTA) on the surface passivation of c-Si by Al2O3 deposited by atmospheric pressure chemical vapour deposition (APCVD) as a function of RTA peak temperature between 500 and 900°C, and for Al2O3 deposition temperatures between 325 and 440°C. The saturation current density J0 of undiffused p-type surfaces is observed either to increase or decrease following RTA depending on the Al2O3 deposition temperature and the RTA peak temperature. The optimum deposition temperature depends on the post-deposition thermal processing to be applied. Films deposited at lower temperatures provide worse passivation after low temperature heat treatment, but maintain this passivation better at higher RTA temperatures. An exceptionally low J0 of 7 fA cm−2, due to the combination of a very low interface state density Dit and unusually high negative fixed charge density Qf, is achieved by the use of a short 500–550°C RTA combined with optimised deposition conditions.

Surface passivation of crystalline silicon by sputtered AlOx/AlNx stacks toward low-cost high-efficiency silicon solar cells

Recently, excellent surface passivation has been achieved for both p- and n-type silicon solar cells using AlOx/SiNx:H stacks deposited by atomic layer deposition and plasma-enhanced chemical vapor deposition. However, alternative materials and deposition methods could provide practical options for large-scale manufacturing of commercial solar cells. In this study we demonstrate that AlOx/AlNx stacks fabricated by reactive radio-frequency magnetron sputtering can provide fairly good surface passivation (Smax of ∼30 cm/s) regardless of AlOx thickness, which is found to be due to the high negative fixed charge density (Qeff of −2.8 × 1012 cm−2) and moderately low interface trap density (Dit of 2.0 × 1011 eV−1·cm−2). The stacks also show fairly good antireflection performance in the visible and near-infrared spectral region. The demonstrated surface passivation and antireflection performance of in situ reactively sputtered AlOx/AlNx stacks make them a promising candidate for a surface-passivating antireflection coating on silicon solar cells.

Detailed study of the effects of interface properties of ozone-based atomic layer deposited AlOx on the surface passivation of crystalline silicon

The effects of interface properties such as a negative fixed charge density and an interface trap density on the surface passivation of crystalline Si by O3-based batch ALD AlOx were studied. High-quality surface passivation with Smax of ∼10 cm/s was obtained from the AlOx samples deposited at 200 °C after annealing. This feature is attributed to the excellent field effect passivation by the high negative fixed charge density of ∼−5 × 1012 cm−2 and chemical passivation, which reduces the interface trap density to ∼1 × 1011 eV−1 cm−2. The annealed AlOx samples deposited at 200 °C also show high thermal stability during firing at 850 °C. Additionally, we found that the formation of a thin SiOx interlayer is essential for the formation of a high negative fixed charge density that induces strong field effect passivation, and that defect passivation at the Si/SiOx interface by diffused hydrogen from AlOx layers is the origin of chemical passivation.

Avidin as a model for charge driven transport into cartilage and drug delivery for treating early stage post-traumatic osteoarthritis

Local drug delivery into cartilage remains a challenge due to its dense extracellular matrix of negatively charged proteoglycans enmeshed within a collagen fibril network. The high negative fixed charge density of cartilage offers the unique opportunity to utilize electrostatic interactions to augment transport, binding and retention of drug carriers. With the goal of developing particle-based drug delivery mechanisms for treating post-traumatic osteoarthritis, our objectives were, first, to determine the size range of a variety of solutes that could penetrate and diffuse through normal cartilage and enzymatically treated cartilage to mimic early stages of OA, and second, to investigate the effects of electrostatic interactions on particle partitioning, uptake and binding within cartilage using the highly positively charged protein, Avidin, as a model. Results showed that solutes having a hydrodynamic diameter ≤10 nm can penetrate into the full thickness of cartilage explants while larger sized solutes were trapped in the tissue's superficial zone. Avidin had a 400-fold higher uptake than its neutral same-sized counterpart, NeutrAvidin, and >90% of the absorbed Avidin remained within cartilage explants for at least 15 days. We report reversible, weak binding (KD ∼ 150 μm) of Avidin to intratissue sites in cartilage. The large effective binding site density (NT ∼ 2920 μm) within cartilage matrix facilitates Avidin's retention, making its structure suitable for particle based drug delivery into cartilage.

Passivation mechanism of thermal atomic layer-deposited Al2O3 films on silicon at different annealing temperatures

Thermal atomic layer-deposited (ALD) aluminum oxide (Al2O3) acquires high negative fixed charge density (Qf) and sufficiently low interface trap density after annealing, which enables excellent surface passivation for crystalline silicon. Qf can be controlled by varying the annealing temperatures. In this study, the effect of the annealing temperature of thermal ALD Al2O3 films on p-type Czochralski silicon wafers was investigated. Corona charging measurements revealed that the Qf obtained at 300°C did not significantly affect passivation. The interface-trapping density markedly increased at high annealing temperature (>600°C) and degraded the surface passivation even at a high Qf. Negatively charged or neutral vacancies were found in the samples annealed at 300°C, 500°C, and 750°C using positron annihilation techniques. The Al defect density in the bulk film and the vacancy density near the SiOx/Si interface region decreased with increased temperature. Measurement results of Qf proved that the Al vacancy of the bulk film may not be related to Qf. The defect density in the SiOx region affected the chemical passivation, but other factors may dominantly influence chemical passivation at 750°C.

Electronic and chemical properties of the c-Si/Al2O3 interface

Using aluminum oxide (Al2O3) films deposited by atomic layer deposition (ALD), the dominant passivation mechanisms at the c-Si/Al2O3 interface, as well as the chemical composition of the interface region, are investigated. The excellent surface passivation quality of thin Al2O3 films is predominantly assigned to a high negative fixed charge density of Qf = − (4 ± 1) × 1012 cm−2, which is located within 1nm of the Si/Al2O3 interface and is independent of the layer thickness. A deterioration of the passivation quality for ultrathin Al2O3 layers is explained by a strong increase in the interface state density, presumably due to an incomplete reaction of the trimethyl-aluminum (TMA) molecules during the first ALD cycles. A high oxygen-to-aluminum atomic ratio resulting from the incomplete adsorption of the TMA molecules is suggested as a possible source of the high negative charge density Qf at the Si/Al2O3 interface.

Very low surface recombination velocities on p- and n-type c-Si by ultrafast spatial atomic layer deposition of aluminum oxide

Using aluminum oxide (Al2O3) films deposited by high-rate spatial atomic layer deposition (ALD), we achieve very low surface recombination velocities of 6.5 cm/s on p-type and 8.1 cm/s on n-type crystalline silicon wafers. Using spatially separated reaction zones instead of the conventional time-sequenced precursor dosing enables growth rates up to 70 nm/min, whereas conventional ALD limits the growth rate to &amp;lt;2 nm/min. The excellent passivation level is predominantly assigned to a high negative fixed charge density of Qf=−(4±1)×1012 cm−2 in the Al2O3 films. We demonstrate an excellent thermal stability of the passivation quality.

Excellent Passivation of p-Type Si Surface by Sol-Gel Al2O3 Films

Al2O3 films with a thickness of about 100 nm synthesized by spin coating and thermally treated are applied for field-induced surface passivation of p-type crystalline silicon. The level of surface passivation is determined by techniques based on photoconductance. An effective surface recombination velocity below 100 cm/s is obtained on 10Ω ·cm p-type c-Si wafers (Cz Si). A high density of negative fixed charges in the order of 1012 cm−2 is detected in the Al2O3 films and its impact on the level of surface passivation is demonstrated experimentally. Furthermore, a comparison between the surface passivation achieved for thermal SiO2 and plasma enhanced chemical vapor deposition SiNx:H films on the same c-Si is presented. The high negative fixed charge density explains the excellent passivation of p-type c-Si by Al2O3.