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1.
Nature ; 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-39322675

ABSTRACT

Unlike non-polar semiconductors such as silicon, the broken inversion symmetry of the wide-bandgap semiconductor gallium nitride (GaN) leads to a large electronic polarization along a unique crystal axis1. This makes the two surfaces of the semiconductor wafer perpendicular to the polar axis substantially different in their physical and chemical properties2. In the past three decades, the cation (gallium) face of GaN has been used for photonic devices such as light-emitting diodes (LEDs) and lasers3-5. Although the cation face has also been predominantly used for electronic devices, the anion (nitrogen) face has recently shown promise for high-electron-mobility transistors (HEMTs) owing to favourable polarization discontinuities6. In this work, we introduce dualtronics, showing that it is possible to make photonic devices on the cation face and electronic devices on the anion face of the same semiconductor wafer. This opens the possibility for making use of both faces of polar semiconductors in a single structure, in which electronic, photonic and acoustic properties can be implemented on opposite faces of the same wafer, markedly enhancing the functional capabilities of this revolutionary semiconductor family.

2.
JACC Cardiovasc Interv ; 17(18): 2141-2153, 2024 Sep 23.
Article in English | MEDLINE | ID: mdl-39243262

ABSTRACT

BACKGROUND: Patients with mitral regurgitation (MR) and morphologic presence of relevant mitral annular calcification (MAC) represent a challenging phenotypic subset with limited treatment options. OBJECTIVES: The aim of this study was to assess the feasibility of transcatheter mitral valve replacement (TMVR) using dedicated devices for the treatment of MAC patients. METHODS: Consecutive patients with symptomatic MR receiving TMVR and with available computed tomography data from the CHOICE-MI (Choice of Optimal Transcatheter Treatment for Mitral Insufficiency) multicenter registry were stratified by the presence of none or mild mitral annular calcification (MACnone/mild) vs moderate or severe mitral annular calcification (MACmod/sev). RESULTS: Among 279 eligible patients (median age = 76.0 years [Q1-Q3: 71.0-81.0 years], EuroSCORE II = 6.2% [Q1-Q3: 3.9%-12.1%]), 222 (79.6%) presented with MACnone/mild and 57 (20.4%) with MACmod/sev. Patients with MACmod/sev had a higher prevalence of extracardiac arteriopathy (P = 0.011) and primary MR (P < 0.001). Although the technical success rate and the extent of MR elimination did not differ, TMVR treatment in MACmod/sev patients was associated with higher rates of postprocedural bleeding complications (P = 0.02) and renal failure (P < 0.001). Functional improvement at the 1- and 2-year follow-up did not differ between groups. At the 2-year follow-up, there were no differences between patients with MACmod/sev and MACnone/mild regarding all-cause mortality (38.5% vs 37.7%; P = 0.76), cardiovascular mortality (21.3% vs 24.9%; P = 0.97), and all-cause mortality or heart failure hospitalization (52.4% vs 46.7%; P = 0.28) CONCLUSIONS: TMVR in patients with MACmod/sev is associated with higher rates of postprocedural complications but similar rates of survival, MR resolution, and functional improvement compared to MACnone/mild. Further studies are necessary to define the role of dedicated TMVR devices in this population. (Choice of Optimal Transcatheter Treatment for Mitral Insufficiency Registry [CHOICE-MI]; NCT04688190).


Subject(s)
Calcinosis , Cardiac Catheterization , Feasibility Studies , Heart Valve Prosthesis Implantation , Heart Valve Prosthesis , Mitral Valve Insufficiency , Mitral Valve , Prosthesis Design , Recovery of Function , Registries , Humans , Aged , Male , Female , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/physiopathology , Mitral Valve Insufficiency/surgery , Mitral Valve Insufficiency/mortality , Mitral Valve/diagnostic imaging , Mitral Valve/physiopathology , Mitral Valve/surgery , Treatment Outcome , Cardiac Catheterization/instrumentation , Cardiac Catheterization/adverse effects , Cardiac Catheterization/mortality , Aged, 80 and over , Time Factors , Heart Valve Prosthesis Implantation/instrumentation , Heart Valve Prosthesis Implantation/adverse effects , Heart Valve Prosthesis Implantation/mortality , Calcinosis/diagnostic imaging , Calcinosis/surgery , Calcinosis/mortality , Calcinosis/physiopathology , Calcinosis/therapy , Risk Factors , Severity of Illness Index , Europe
3.
Nat Mater ; 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39261721

ABSTRACT

Shape morphing is vital to locomotion in microscopic organisms but has been challenging to achieve in sub-millimetre robots. By overcoming obstacles associated with miniaturization, we demonstrate microscopic electronically configurable morphing metasheet robots. These metabots expand locally using a kirigami structure spanning five decades in length, from 10 nm electrochemically actuated hinges to 100 µm splaying panels making up the ~1 mm robot. The panels are organized into unit cells that can expand and contract by 40% within 100 ms. These units are tiled to create metasheets with over 200 hinges and independent electronically actuating regions that enable the robot to switch between multiple target geometries with distinct curvature distributions. By electronically actuating independent regions with prescribed phase delays, we generate locomotory gaits. These results advance a metamaterial paradigm for microscopic, continuum, compliant, programmable robots and pave the way to a broad spectrum of applications, including reconfigurable micromachines, tunable optical metasurfaces and miniaturized biomedical devices.

4.
Nat Mater ; 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39227466

ABSTRACT

Transition metal nitride (TMN-) based materials have recently emerged as promising non-precious-metal-containing electrocatalysts for the oxygen reduction reaction (ORR) in alkaline media. However, the lack of fundamental understanding of the oxide surface has limited insights into structure-(re)activity relationships and rational catalyst design. Here we demonstrate how a well-defined TMN can dictate/control the as-formed oxide surface and the resulting ORR electrocatalytic activity. Structural characterization of MnN nanocuboids revealed that an electrocatalytically active Mn3O4 shell grew epitaxially on the MnN core, with an expansive strain along the [010] direction to the surface Mn3O4. The strained Mn3O4 shell on the MnN core exhibited an intrinsic activity that was over 300% higher than that of pure Mn3O4. A combined electrochemical and computational investigation indicated/suggested that the enhancement probably originates from a more hydroxylated oxide surface resulting from the expansive strain. This work establishes a clear and definitive atomistic picture of the nitride/oxide interface and provides a comprehensive mechanistic understanding of the structure-reactivity relationship in TMNs, critical for other catalytic interfaces for different electrochemical processes.

5.
Angew Chem Int Ed Engl ; : e202416480, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-39278822

ABSTRACT

Covalent organic frameworks linked by carbon-carbon double bonds (C=C COFs) are an emerging class of crystalline, porous, and conjugated polymeric materials with potential applications in organic electronics, photocatalysis, and energy storage. Despite the rapidly growing interest in sp2 carbon-conjugated COFs, only a small number of closely related condensation reactions have been successfully employed for their synthesis to date. Herein, we report the first example of a C=C COF, CORN-COF-1 (CORN = Cornell University), prepared by N-heterocyclic carbene (NHC) dimerization. In-depth characterization reveals that CORN-COF-1 possesses a two-dimensional layered structure and hexagonal guest-accessible pores decorated with a high density of strongly reducing tetraazafulvalene linkages. Exposure of CORN-COF-1 to tetracyanoethylene (TCNE, E1/2 = 0.13 V and -0.87 V vs. SCE) oxidizes the COF and encapsulates the radical anion TCNE•- and the dianion TCNE2- as guest molecules, as confirmed by spectroscopic and magnetic analysis. Notably, the reactive TCNE•- radical anion, which generally dimerizes in the solid state, is uniquely stabilized within the pores of CORN-COF-1. Overall, our findings broaden the toolbox of reactions available for the synthesis of redox-active C=C COFs, paving the way for the design of novel materials.

6.
JNCI Cancer Spectr ; 8(5)2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39180334

ABSTRACT

BACKGROUND: Adiposity has been characterized as a modifiable risk factor for prostate cancer. Its association with outcomes after prostate cancer diagnosis, however, must be better understood, and more evidence is needed to facilitate the development of lifestyle guidance for patients with prostate cancer. METHODS: We investigated the associations between adiposity indices close to prostate cancer diagnosis (up to 2 years before or up to 5 years after diagnosis) and mortality in 1968 men of the European Prospective Investigation into Cancer and Nutrition cohort. Men were followed up for a median of 9.5 years. Cox proportional hazards models were adjusted for age and year of diagnosis, disease stage and grade, and smoking history and stratified by country. RESULTS: Each 5-unit increment in prediagnosis or postdiagnosis body mass index combined was associated with a 30% higher rate of all-cause mortality and a 49% higher rate of prostate cancer-specific mortality. Similarly, each 5-unit increment in prediagnosis body mass index was associated with a 35% higher rate of all-cause mortality and a 51% higher rate of prostate cancer-specific mortality. The associations were less strong for postdiagnosis body mass index, with a lower number of men in analyses. Less clear positive associations were shown for waist circumference, hip circumference, and waist to hip ratio, but data were limited. CONCLUSIONS: Elevated levels of adiposity close to prostate cancer diagnosis could lead to higher risk of mortality; therefore, men are encouraged to maintain a healthy weight. Additional research is needed to confirm whether excessive adiposity after prostate cancer diagnosis could worsen prognosis.


Subject(s)
Adiposity , Body Mass Index , Proportional Hazards Models , Prostatic Neoplasms , Waist Circumference , Waist-Hip Ratio , Humans , Male , Prostatic Neoplasms/mortality , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/pathology , Middle Aged , Prognosis , Prospective Studies , Risk Factors , Aged , Obesity/complications , Europe/epidemiology , Cause of Death
8.
Int J Cardiol Heart Vasc ; 53: 101472, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39171287

ABSTRACT

Pulmonary hypertension (PH) is a common and prognostically important complication of mitral regurgitation (MR). Mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) are traditionally used to diagnose PH, however these indices measure static rather than pulsatile load, leading to an incomplete representation of pulmonary vascular load on the right ventricle (RV). Pulmonary arterial compliance (PAC) is one method for quantifying pulsatile load, and is both a stronger predictor of prognosis in left heart failure, as well as a more sensitive measure of early pulmonary vascular dysfunction than PVR. With the expansion of transcatheter mitral and tricuspid valve therapies, there is renewed interest to more accurately define the load imposed by the pulmonary vasculature on the RV, especially in the early phase, prior to the onset of chronic PH. This review discusses the pathophysiology of pH in left heart failure and MR, the utility of PAC as a measure of RV afterload, and its calculation for clinical use and interpretation, underlining the utility of PAC as an adjunct for assessing pulmonary vascular haemodynamics.

10.
EuroIntervention ; 20(14): e887-e897, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39007829

ABSTRACT

BACKGROUND: Transcatheter mitral valve replacement (TMVR) is a therapeutic option for patients with severe mitral regurgitation (MR) who are ineligible for conventional surgery. There are limited data on the outcomes of large patient cohorts treated with TMVR. AIMS: This study aimed to investigate the outcomes and predictors of mortality for patients treated with transapical TMVR. METHODS: This analysis represents the clinical experience of all patients enrolled in the Tendyne Expanded Clinical Study. Patients with symptomatic MR underwent transapical TMVR with the Tendyne system between November 2014 and June 2020. Outcomes and adverse events up to 2 years, as well as predictors of short-term mortality, were assessed. RESULTS: A total of 191 patients were treated (74.1±8.0 years, 62.8% male, Society of Thoracic Surgeons Predicted Risk of Mortality 7.7±6.6%). Technical success was achieved in 96.9% (185/191), and there were no intraprocedural deaths. At 30-day, 1- and 2-year follow-up, the rates of all-cause mortality were 7.9%, 30.8% and 40.5%, respectively. Complete MR elimination (MR <1+) was observed in 99.3%, 99.1% and 96.3% of patients, respectively. TMVR treatment resulted in consistent improvement of New York Heart Association Functional Class and quality of life up to 2 years (both p<0.001). Independent predictors of early mortality were age (odds ratio [OR] 1.11; p=0.003), pulmonary hypertension (OR 3.83; p=0.007), and institutional experience (OR 0.40; p=0.047). CONCLUSIONS: This study investigated clinical outcomes in the full cohort of patients included in the Tendyne Expanded Clinical Study. The Tendyne TMVR system successfully eliminated MR with no intraprocedural deaths, resulting in an improvement in symptoms and quality of life. Continued refinement of clinical and echocardiographic risks will be important to optimise longitudinal outcomes.


Subject(s)
Cardiac Catheterization , Heart Valve Prosthesis Implantation , Mitral Valve Insufficiency , Mitral Valve , Humans , Mitral Valve Insufficiency/surgery , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/physiopathology , Mitral Valve Insufficiency/mortality , Male , Female , Heart Valve Prosthesis Implantation/methods , Heart Valve Prosthesis Implantation/adverse effects , Heart Valve Prosthesis Implantation/instrumentation , Aged , Mitral Valve/surgery , Mitral Valve/diagnostic imaging , Mitral Valve/physiopathology , Treatment Outcome , Aged, 80 and over , Cardiac Catheterization/methods , Cardiac Catheterization/adverse effects , Cardiac Catheterization/instrumentation , Heart Valve Prosthesis , Risk Factors , Middle Aged
11.
Heart Rhythm ; 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38971416

ABSTRACT

BACKGROUND: Cardiac resynchronization therapy (CRT) is associated with challenges such as elevated capture thresholds, diaphragmatic stimulation, and lead instability. OBJECTIVE: This study aimed to assess the long-term safety and efficacy of the quadripolar CRT-defibrillator (CRT-D) device system with the Quartet 1458Q left ventricular (LV) lead in a CRT-indicated population observed for 5 years and to evaluate all-cause mortality and impact of baseline characteristics on survival through 5 years. METHODS: Patients indicated for a CRT-D system were observed every 6 months after implantation for 5 years, and device performance and adverse events were assessed at each visit. The 3 primary end points were freedom from quadripolar CRT-D system-related complications through 5 years, freedom from Quartet 1458Q LV lead-related complications through 5 years, and mean programmed pacing capture threshold at 5 years. RESULTS: The study enrolled 1970 participants at 71 sites. The quadripolar CRT-D system was successfully implanted in 97.2% of participants. Freedom from quadripolar CRT-D device system-related complications through 5 years was 89.7%. Freedom from Quartet 1458Q LV lead-related complications through 5 years was 95.7%; 3.49% of participants had LV lead-related complications, and an overall LV lead complication rate was 0.0122 event per patient-year. The mean LV pacing capture threshold was 1.52 ± 1.01 V at 5 years. The 5-year survival rate was 67.4%. CONCLUSION: The quadripolar CRT-D system with the Quartet 1458Q LV lead exhibited low rates of complications and stable electrical performance through 5 years of follow-up and suggested a higher 5-year survival rate compared with traditional CRT systems.

12.
Eur Heart J Imaging Methods Pract ; 2(2): qyae026, 2024 Apr.
Article in English | MEDLINE | ID: mdl-39045464

ABSTRACT

Aims: The morphology and function of the left atrium (LA) are intimately tied to left ventricular loading conditions. Data pertaining to the effect of transcatheter aortic valve replacement (TAVR) on LA function and geometry are scarce. The aim of the study was to quantify associations between TAVR and LA remodelling by pooling available data from published observational studies. Methods and results: A systematic review and meta-analysis were performed. Studies reporting serial LA speckle-tracking echocardiographic (STE) data, before and after TAVR, were included. Other outcome data included LA area and indexed volume (LAVi) and standard chamber measurements. Outcomes were stratified by timing of follow-up echocardiography: early (<6 months) or late (≥6 months). Twelve studies were included, comprising 1066 patients. The mean reduction in LAVi was 2.72 mL/m2 [95% confidence interval (CI) 1.37-4.06, P < 0.01]. LA reservoir function improved overall by a mean difference (MD) of 3.71% (95% CI 1.82-5.6, P < 0.01), although there was significant heterogeneity within the pooled studies (I 2 = 87.3%). Significant improvement in reservoir strain was seen in both early follow-up (MD 3.1%, P < 0.01) and late follow-up studies (MD 4.48%, P = 0.03), but heterogeneity remained high (I 2 = 65.23 and 94.4%, respectively). Six studies reported a change in LA contractile function, which recovered in the early follow-up studies (MD 2.26, P < 0.01), but not in the late group (MD 1.41, P = 0.05). Pooled improvement in LA booster function was 1.96% (95% CI 1.11-2.8, P < 0.01). Conclusion: TAVR is associated with significant negative LA remodelling, and an improvement in LA mechanics, quantified by STE. The prognostic implications of these findings require further study.

13.
J Am Chem Soc ; 146(26): 17613-17617, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38885442

ABSTRACT

Synthesis of high-entropy oxide (HEO) nanocrystals has focused on increasing the temperature in the entropy term (T(ΔS)) to overcome the enthalpy term. However, these high temperatures lead to large, polydisperse nanocrystals. In this work, we leverage the low solubility product (Ksp) of metal oxides and optimize the Lewis-acid-catalyzed esterification reaction for equal rate production of the cation monomers to synthesize HEO nanocrystals at low temperatures, producing the smallest (<4 nm) and most monodisperse (<15% size dispersity) HEOs to date. We apply these HEO nanocrystals as electrocatalysts, exhibiting promising activity toward the oxygen evolution reaction in alkaline media, with an overpotential of 345 mV at 10 mA/cm2.

15.
Nat Commun ; 15(1): 5400, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38926403

ABSTRACT

Oxide heterostructures exhibit a vast variety of unique physical properties. Examples are unconventional superconductivity in layered nickelates and topological polar order in (PbTiO3)n/(SrTiO3)n superlattices. Although it is clear that variations in oxygen content are crucial for the electronic correlation phenomena in oxides, it remains a major challenge to quantify their impact. Here, we measure the chemical composition in multiferroic (LuFeO3)9/(LuFe2O4)1 superlattices, mapping correlations between the distribution of oxygen vacancies and the electric and magnetic properties. Using atom probe tomography, we observe oxygen vacancies arranging in a layered three-dimensional structure with a local density on the order of 1014 cm-2, congruent with the formula-unit-thick ferrimagnetic LuFe2O4 layers. The vacancy order is promoted by the locally reduced formation energy and plays a key role in stabilizing the ferroelectric domains and ferrimagnetism in the LuFeO3 and LuFe2O4 layers, respectively. The results demonstrate pronounced interactions between oxygen vacancies and the multiferroic order in this system and establish an approach for quantifying the oxygen defects with atomic-scale precision in 3D, giving new opportunities for deterministic defect-enabled property control in oxide heterostructures.

16.
J Cardiovasc Dev Dis ; 11(6)2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38921682

ABSTRACT

AIM: To assess the acute effect of empagliflozin versus dapagliflozin administration on flow-mediated vasodilation in patients with type 2 diabetes mellitus. DESIGN: A double-blind clinical trial, at the Experimental and Clinical Therapeutics Institute, University Health Sciences Center, at the Universidad de Guadalajara, in inpatients with T2D according to the 2023 ADA criteria. METHODS: Thirty patients (15 males and 15 females), aged between 35 and 65 years, were included in this study, according to the 2023 ADA criteria. The eligible patients were randomly assigned to three groups: empagliflozin 25 mg once daily, dapagliflozin 10 mg once daily, or placebo once daily. Anthropometric parameters were taken using validated techniques. FMD was measured using a high-resolution semiautomatic ultrasound UNEX-EF 38G (UNEX Co., Ltd., Nagoya, Japan). Arterial tension was determined with the OMRON electronic digital sphygmomanometer (HEM 907 XL, Kyoto, Japan). RESULTS: The group of patients who received empagliflozin had a significantly lower baseline flow-mediated dilation (FMD) compared to the group receiving dapagliflozin (p = 0.017); at the end of this study, the empagliflozin group achieved a comparable FMD to the dapagliflozin group (p = 0.88). CONCLUSION: After the treatment period, the empagliflozin and dapagliflozin groups achieved similar FMD, suggesting a class effect.

17.
Catheter Cardiovasc Interv ; 104(1): 155-166, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38819861

ABSTRACT

Frailty is a common clinical syndrome that portends poor peri-procedural outcomes and increased mortality following transcatheter valve interventions. We reviewed frailty assessment tools in transcatheter intervention cohorts to recommend a pathway for preprocedural frailty assessment in patients referred for transcatheter valve procedures, and evaluated current evidence for frailty interventions and their efficacy in transcatheter intervention. We recommend the use of a frailty screening instrument to identify patients as frail, with subsequent referral for comprehensive geriatric assessment in these patients, to assist in selecting appropriate patients and then optimizing them for transcatheter valve interventions. Interventions to reduce preprocedural frailty are not well defined, however, data from limited cohort studies support exercise-based interventions to increase functional capacity and reduce frailty in parallel with preprocedural medical optimization.


Subject(s)
Frail Elderly , Frailty , Geriatric Assessment , Humans , Frailty/diagnosis , Frailty/physiopathology , Treatment Outcome , Risk Factors , Aged , Risk Assessment , Aged, 80 and over , Age Factors , Cardiac Catheterization/adverse effects , Functional Status , Female , Male , Patient Selection , Heart Valve Prosthesis Implantation/adverse effects , Heart Valve Prosthesis Implantation/instrumentation , Predictive Value of Tests , Transcatheter Aortic Valve Replacement/adverse effects , Transcatheter Aortic Valve Replacement/mortality , Clinical Decision-Making , Heart Valve Diseases/physiopathology , Heart Valve Diseases/surgery , Heart Valve Diseases/mortality , Heart Valve Diseases/diagnostic imaging , Heart Valve Diseases/therapy , Health Status
18.
Metab Eng ; 85: 26-34, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38802041

ABSTRACT

Integration of novel compounds into biological processes holds significant potential for modifying or expanding existing cellular functions. However, the cellular uptake of these compounds is often hindered by selectively permeable membranes. We present a novel bacterial transport system that has been rationally designed to address this challenge. Our approach utilizes a highly promiscuous sulfonate membrane transporter, which allows the passage of cargo molecules attached as amides to a sulfobutanoate transport vector molecule into the cytoplasm of the cell. These cargoes can then be unloaded from the sulfobutanoyl amides using an engineered variant of the enzyme γ-glutamyl transferase, which hydrolyzes the amide bond and releases the cargo molecule within the cell. Here, we provide evidence for the broad substrate specificity of both components of the system by evaluating a panel of structurally diverse sulfobutanoyl amides. Furthermore, we successfully implement the synthetic uptake system in vivo and showcase its functionality by importing an impermeant non-canonical amino acid.


Subject(s)
Escherichia coli , Escherichia coli/metabolism , Escherichia coli/genetics , Membrane Transport Proteins/metabolism , Membrane Transport Proteins/genetics , Metabolic Engineering , gamma-Glutamyltransferase/metabolism , gamma-Glutamyltransferase/genetics
19.
Nat Commun ; 15(1): 3828, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38714653

ABSTRACT

Stabilization of topological spin textures in layered magnets has the potential to drive the development of advanced low-dimensional spintronics devices. However, achieving reliable and flexible manipulation of the topological spin textures beyond skyrmion in a two-dimensional magnet system remains challenging. Here, we demonstrate the introduction of magnetic iron atoms between the van der Waals gap of a layered magnet, Fe3GaTe2, to modify local anisotropic magnetic interactions. Consequently, we present direct observations of the order-disorder skyrmion lattices transition. In addition, non-trivial topological solitons, such as skyrmioniums and skyrmion bags, are realized at room temperature. Our work highlights the influence of random spin control of non-trivial topological spin textures.

20.
Biotechnol Bioeng ; 121(7): 2225-2233, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38678541

ABSTRACT

Process in-line monitoring and control are crucial to optimize the productivity of bioprocesses. A frequently applied Process Analytical Technology (PAT) tool for bioprocess in-line monitoring is Raman spectroscopy. However, evaluating bioprocess Raman spectra is complex and calibrating state-of-the-art statistical evaluation models is effortful. To overcome this challenge, we developed an Indirect Hard Modeling (IHM) prediction model in a previous study. The combination of Raman spectroscopy and the IHM prediction model enables non-invasive in-line monitoring of glucose and ethanol mass fractions during yeast fermentations with significantly less calibration effort than comparable approaches based on statistical models. In this study, we advance this IHM-based approach and successfully demonstrate that the combination of Raman spectroscopy and IHM is capable of not only bioprocess monitoring but also bioprocess control. For this purpose, we used this combination's in-line information as input of a simple on-off glucose controller to control the glucose mass fraction in Saccharomyces cerevisiae fermentations. When we performed two of these fermentations with different predefined glucose set points, we achieved similar process control quality as approaches using statistical models, despite considerably smaller calibration effort. Therefore, this study reaffirms that the combination of Raman spectroscopy and IHM is a powerful PAT tool for bioprocesses.


Subject(s)
Ethanol , Glucose , Saccharomyces cerevisiae , Spectrum Analysis, Raman , Spectrum Analysis, Raman/methods , Saccharomyces cerevisiae/metabolism , Glucose/metabolism , Glucose/analysis , Ethanol/metabolism , Ethanol/analysis , Fermentation , Models, Biological , Bioreactors
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