3D Micro Research Articles

Grayscale Lithography and a Brief Introduction to Other Widely Used Lithographic Methods: A State-of-the-Art Review

Lithography serves as a fundamental process in the realms of microfabrication and nanotechnology, facilitating the transfer of intricate patterns onto a substrate, typically in the form of a wafer or a flat surface. Grayscale lithography (GSL) is highly valued in precision manufacturing and research endeavors because of its unique capacity to create intricate and customizable patterns with varying depths and intensities. Unlike traditional binary lithography, which produces discrete on/off features, GSL offers a spectrum of exposure levels. This enables the production of complex microstructures, diffractive optical elements, 3D micro-optics, and other nanoscale designs with smooth gradients and intricate surface profiles. GSL plays a crucial role in sectors such as microelectronics, micro-optics, MEMS/NEMS manufacturing, and photonics, where precise control over feature depth, shape, and intensity is critical for achieving advanced functionality. Its versatility and capacity to generate tailored structures make GSL an indispensable tool in various cutting-edge applications. This review will delve into several lithographic techniques, with a particular emphasis on masked and maskless GSL methods. As these technologies continue to evolve, the future of 3D micro- and nanostructure manufacturing will undoubtedly assume even greater significance in various applications.

Numerical investigation on machining of additively manufactured CFRP composite with different build orientations and layer widths

Additive manufacturing (AM) is now a widely researched manufacturing technology in the past two decades to adopt in industry for its added advantage of customization and adopting complex geometries with comparatively low buy-to-fly ratio. Carbon fiber reinforced polymer (CFRP) composite has found applications in different high-performance industries for its greatest benefit of high strength-to-weight ratio. Additive manufacturing of CFRP composite (AM-CFRP) opens up the possibility of enhancing mechanical strength using different printing orientations and enables producing complex shapes maintaining sustainable manufacturing perspective. However, Limitation of AM parts of having surface irregularities and questionable dimensional accuracies. To use AM-CFRP parts in high precision assembly or industrial applications, post processing machining is often required to meet the customers’ specification of geometrical tolerances and acceptable surface finish. In this study, the influence of AM parameters on machinability of AM-CFRP composite has been evaluated using finite element analysis (FEA) based numerical simulation. The slot milling operation was simulated with a tungsten carbide end milling tool and AM-CFRP workpiece with four different printing directions, i.e., 0°-90°, 45°-135°, 0°-90°-45°-135°, two different layer widths, i.e., 50 µm and 100 µm, and two in-fill patterns, i.e., solid and perforated structures. The machinability of the 3D printed CFRP has been analyzed based on cutting forces, stress at first contact and maximum stress generation, and temperature increases at the interface during slot milling of AM-CFRP under different AM parameters. Evolution of failure mechanisms of AM-CFRPs under various machining conditions, such as, delamination, matrix rupture etc., have been discussed and chip and burr formation mechanisms have been analyzed. Finite Element analysis (FEA) package ABAQUS/Explicit was used to model 3D micro slot milling operation of AM-CFRP workpiece with appropriate damage and constitutive models, such as, damage initiation, progression and cohesion in adjacent passes and layers.

173 (PB161): Ex vivo 3D micro tumor testing platform to guide patient stratification for clinical development of ADCs

173 (PB161): Ex vivo 3D micro tumor testing platform to guide patient stratification for clinical development of ADCs

Multi-view neural 3D reconstruction of micro- and nanostructures with atomic force microscopy

Atomic Force Microscopy (AFM) is a widely employed tool for micro- and nanoscale topographic imaging. However, conventional AFM scanning struggles to reconstruct complex 3D micro- and nanostructures precisely due to limitations such as incomplete sample topography capturing and tip-sample convolution artifacts. Here, we propose a multi-view neural-network-based framework with AFM, named MVN-AFM, which accurately reconstructs surface models of intricate micro- and nanostructures. Unlike previous 3D-AFM approaches, MVN-AFM does not depend on any specially shaped probes or costly modifications to the AFM system. To achieve this, MVN-AFM employs an iterative method to align multi-view data and eliminate AFM artifacts simultaneously. Furthermore, we apply the neural implicit surface reconstruction technique in nanotechnology and achieve improved results. Additional extensive experiments show that MVN-AFM effectively eliminates artifacts present in raw AFM images and reconstructs various micro- and nanostructures, including complex geometrical microstructures printed via two-photon lithography and nanoparticles such as poly(methyl methacrylate) (PMMA) nanospheres and zeolitic imidazolate framework-67 (ZIF-67) nanocrystals. This work presents a cost-effective tool for micro- and nanoscale 3D analysis.

Influence of annealing temperature on 3D surface stereometric analysis in C-Ni films

PurposeThe purpose of this paper is to study the correlation between the thicknesses of the C–Ni films that have been prepared by RF-magnetron sputtering on quartz substrates and their three-dimensional (3D) micro morphology. In this work by AFM images, this paper studied stereo metric analysis of these films.Design/methodology/approachThe C–Ni films have been prepared by RF-magnetron sputtering on quartz substrates using a mosaic target consisting of pure graphite and strips of pure nickel approximately 2 cm2 attached to the graphite race track. The field emission scanning electronic microscopy (FESEM) images were used for the morphological characterization.FindingsThe histogram peaks are zero for all samples and the histograms are almost symmetric around zero. Temperature did not have much effect on the degree of isolation, so all four diagrams have similar results. The qualitative observations through statistical parameters of the 3D surface texture revealed that the smoothest surface has been obtained for C-Ni films annealed at 500 °C (Sa, Sq, Sz and Sv have the lower values), while the most irregular topography has been found for C-Ni films annealed at 300 °C (the fractal dimension D = 2.01 ± 0.131).Originality/valueAs shown in FESEM images, the size of the particles was increased for films deposited from 300 ºC to 800ºC; however, at 1000ºC, it decreased significantly. The histogram peaks are zero for all samples and the histograms were almost symmetric around zero. Also, the largest and lowest root mean heights (Sq) belong to films at 300 °C and 500 °C. Furthermore, the more irregular surface was found at 300 °C, and the more regular surface was found at 500 °C. As the temperature was increased to 800 °C, the values of the IAPSD function increased systematically, and then the values of the IAPSD function was decreased in the fourth sample. The surface skewness of samples annealed at 1000 °C was positive which confirms the lack of dominance of cavities on their surface with the highest amount of C-Ni films at 800 °C.

The phosphorous-doped 2D nanosheet assembled 3D Mn2V2O7 microflowers on Ni foam as a binder-free electrode for high energy density asymmetric supercapacitor application

In recent times, transition-metal oxides have been recognized as highly promising candidates for supercapacitor applications. Nevertheless, their progress in diverse fields has been hindered by challenges such as poor electrical conductivity and a shortage of active reaction centers. Doping heteroatoms would overcome these drawbacks and enhance the supercapacitor properties in transition metal oxides. Herein, the phosphorous-doped 2D nanosheet assembled 3D Mn2V2O7 micro flowers were grown on the Nickel foam using the hydrothermal method and successively phosphatized in a tube furnace, which was utilized as a binder-free supercapacitor electrode. The synthesis process involved varying the concentration of phosphorus (P), resulting in the successful formation of uniform P-decorated Mn2V2O7 microflowers. The unique microflower structure and doping P into the Mn2V2O7 material enhance the electrochemical properties with a specific capacity of 850C g−1 (1545 F g−1) at 1 A g−1 in a three-electrode cell. Moreover, the assembled Mn2V2O7–600/NF//AC device delivers a specific capacity of 258C g−1 (211 F g−1) at 1 A g−1 with a remarkable rate of 47 % at a high current density of 20 Ag −1. The device achieved a maximum energy density of 43.2 Wh kg−1 at a power density of 604.7 W kg−1, and it maintained 91 % of initial capacity after 10,000 charge/discharge cycles at 20 A g−1. These results suggest that the P-doping 2D nanosheet assembled 3D Mn2V2O7 could be promising electrode materials for supercapacitor applications.

Capillary trapping of various nanomaterials on additively manufactured scaffolds for 3D micro-/nanofabrication

High-precision additive manufacturing technologies, such as two-photon polymerization, are mainly limited to photo-curable polymers and currently lacks the possibility to produce multimaterial components. Herein, we report a physically bottom-up assembly strategy that leverages capillary force to trap various nanomaterials and assemble them onto three-dimensional (3D) microscaffolds. This capillary-trapping strategy enables precise and uniform assembly of nanomaterials into versatile 3D microstructures with high uniformity and mass loading. Our approach applies to diverse materials irrespective of their physiochemical properties, including polymers, metals, metal oxides, and others. It can integrate at least four different material types into a single 3D microstructure in a sequential, layer-by-layer manner, opening immense possibilities for tailored functionalities on demand. Furthermore, the 3D microscaffolds are removable, facilitating the creation of pure material-based 3D microstructures. This universal 3D micro-/nanofabrication technique with various nanomaterials enables the creation of advanced miniature devices with potential applications in multifunctional microrobots and smart micromachines.

An optimal toolpath planning for realizing 3D micro metallic features via selective jet electrodeposition (SJED) process

An optimal toolpath planning for realizing 3D micro metallic features via selective jet electrodeposition (SJED) process

A Fluorescence-based Method to Reaccess Root Canals in Endodontically Treated Teeth: A Micro–Computed Tomography Tridimensional Assessment

IntroductionThe aim of this study was to evaluate the volume of dentin removal and the volume of remnants of restorative material after the removal of an esthetic restorative coronal set and cervical barrier in endodontically treated mandibular molars with the aid of different magnification methods using 3-dimensional (3D) micro–computed tomographic (micro-CT) morphometric analysis. MethodsA sample of 30 mandibular first molars (N = 30) was used. All teeth were endodontically treated, and the specimens were initially scanned using micro-CT imaging and reconstructed. The molars were filled by a single-cone technique, and immediately the material at the initial 2-mm cervical level was removed. Cervical barriers were confected using ionomer glass cement with fluorescein 0.1%, filling the 2 mm at the cervical level of the canals and an additional 2 mm as the base. The coronal restoration set was performed using esthetic resin composites. A simulated tooth aging process was performed with 20,000 thermocycling cycles. The sample was distributed into the following 3 groups (n = 10) for the removal of the restoration set and cervical barrier with diamond burs based on the magnification aid: no magnification aid (naked eye), operative microscope aid, and REVEAL device (Design for Vision Inc, Bohemia, NY) aid. After removal, the final 3D micro-CT scanning and reconstruction were conducted with the same parameters as the initial scanning, and superposition of the final and initial scanning was performed. Morphometric analysis was conducted using CTAn software (Bruker microCT, Kontich, Belgium) to assess the volume of remnant restorative material (mm³), the volume of dentin removal (mm³), and the direction and site of dentin removal. Data were analyzed using 1-Way analysis of variance (P < .05). ResultsThe REVEAL group showed better results regarding the volume of remnant material (3.17 ± 1.65) and the percentage of dentin removal (2.56 ± 1.34). The microscope group showed no statistical difference compared with the REVEAL group regarding dentin removal (3.30 ± 1.48) and was statistically similar to the naked eye group in the volume of remnant material (9.63 ± 4.33). The naked eye group showed the worst results for the volume of remnant material (7.60 ± 2.68) and the percentage of dentin removal (6.60 ± 3.70). ConclusionsThe use of fluorescence associated with magnification was the method that presented the best results, with lower percentages of dentin removal and smaller volumes of remaining restorative material. This is an innovative technology in endodontics that shows potential to overcome the challenge of reaccessing root canals in the context of endodontic retreatment.

Study of anisotropy in polydispersed 2D micro and nano-composites by Elbow and K-Means clustering methods

A new two-dimensional polydisperse model for testing multiphase composites is developed. The verification of the model is carried out based on the microstructure of two composites obtained in the ex-situ and in-situ techniques produced in the Friction Stir Processing (Al–Si–Cu/SiCp) and the Self-propagating High temperature Synthesis (Al/nano-TiCp). The examined microstructure is considered on macro-, meso- and micro- levels. Besides the reinforcement phase distribution concentration, an anisotropy coefficient κ is calculated for every meso-cell. It is the cumulative vector parameter that characterizes the spatial two-point correlation of inclusions. In particular, κ determines the principal axes of the effective conductivity tensor over a meso-cell. The anisotropy spatial distribution ϰ(x) is introduced as the discrete function of values κ calculated over meso-cells centered at the point x. This new distribution ϰ(x) accumulates the geometrical information of the considered microstructure. A computational experiment is designed and carried out in order to study the influence of the reinforcement phase redistribution on the anisotropy. Therefore, it adequately describes the anisotropy of fields in composites modeling thermal and electric conductivity, diffusion, and elastic antiplane deformation. The results of the computational experiments are analyzed using the Elbow and K-Means clustering machine learning algorithm. The detailed analysis is carried out to divide the data set into up to 5 clusters. A research hypothesis concerning the criterion of isotropy of the distribution of reinforcing phase particles in the composite structure is formulated

Bioprinting native-like 3D micro breast cancer tissues utilizing existing cancer cell lines

Bioprinting native-like 3D micro breast cancer tissues utilizing existing cancer cell lines

Structural evolution in S-vacancy-rich Co@Co9S8 during selective benzyl alcohol electrooxidation reaction

Electrooxidation of organics using electrons as oxidants is a clean approach to produce commodity chemicals. However, designing an electrocatalyst with superior performance at low cell voltage remains a challenge. In this study, a series of VS-Co@Co9S8 electrocatalysts were fabricated by thermal reduction method using MOFs as templates. The catalytic oxidation performance and reaction mechanism of such specimens for benzyl alcohol were comprehensively analyzed by electrochemical measurement method and ex-situ structure characterization. The results show that Co@Co9S8-30 M has a unique three-dimensional (3D) micro cubic structure with abundant S vacancy (VS). These features accelerate the electrons and substrate transfer as well as provide plentiful active sites for benzyl alcohol electrooxidation reaction (BAOR). Consequently, the Co@Co9S8-30 M presented outstanding catalytic activity. The overpotential of 10 mA cm−2 (η10) was only 265.4 mV for BAOR. The conversion rate and benzoic acid selectivity were achieved to 72% and 90%, respectively. Particularly, the formation rate of benzoic acid was 7.247 mmol·gcat.−1·h−1. Moreover, the Co@Co9S8-30 M exhibited superior durability over 135 h. The coordination number of octahedral metal sites in Co9S8 did not match the number of Co 3 d orbital electrons, resulting in the weakening of bonding strength between Co and S elements. Thus, the Co@Co9S8 was reconstructed to Co3O4@CoOOH. Based on this assessment, the Co3O4@CoOOH was the active site of BAOR. This work provides theoretical guidance for the design of Co-based catalysts.

Free-standing microscale photonic lantern spatial mode (De-)multiplexer fabricated using 3D nanoprinting

Photonic lantern (PL) spatial multiplexers show great promise for a range of applications, such as future high-capacity mode division multiplexing (MDM) optical communication networks and free-space optical communication. They enable efficient conversion between multiple single-mode (SM) sources and a multimode (MM) waveguide of the same dimension. PL multiplexers operate by facilitating adiabatic transitions between the SM arrayed space and the single MM space. However, current fabrication methods are forcing the size of these devices to multi-millimeters, making integration with micro-scale photonic systems quite challenging. The advent of 3D micro and nano printing techniques enables the fabrication of freestanding photonic structures with a high refractive index contrast (photopolymer-air). In this work we present the design, fabrication, and characterization of a 6-mode mixing, 375 µm long PL that enables the conversion between six single-mode inputs and a single six-mode waveguide. The PL was designed using a genetic algorithm based inverse design approach and fabricated directly on a 7-core fiber using a commercial two-photon polymerization-based 3D printer and a photopolymer. Although the waveguides exhibit high index contrast, low insertion loss (−2.6 dB), polarization dependent (−0.2 dB) and mode dependent loss (−4.4 dB) were measured.

A microchip gas chromatography column assembly with a 3D metal printing micro column oven and a flexible stainless-steel column

In this work, a microchip gas chromatography (GC) column assembly utilizing a three-dimensional (3D) printed micro oven and a flexible stainless steel capillary column was developed. The assembly's performance and separation capabilities were characterized. The key components include a 3D printed aluminum plate (7.50 × 7.50 × 0.16 cm) with a 3-meter-long circular spiral channel, serving as the oven, and the column coiled on the channel with an inner diameter of 320 μm and a stationary phase of OV-1. A heating ceramic plate was affixed on the opposite side of the plate. The assembly weighed 40.3 g. The design allows for easy disassembly, or stacking of heating devices and columns, enabling flexibility in adjusting column length. When using n-C13 as the test analyte at 140 °C, a retention factor (k) was 8.5, and 7797 plates (2599 plates/m) were obtained. The assembly, employing resistance heating, demonstrated effective separation performance for samples containing alkanes, aromatics, alcohols and ketones, with good reproducibility. The reduction in theoretical plates compared to oven heating was only 2.95 %. In the boiling point range of C6 to C18, rapid temperature programming (120 °C/min) was achieved with a power consumption of 119.512 W. The assembly was successfully employed to separate benzene series compounds, gasoline and volatile organic compounds (VOCs), demonstrating excellent separation performance. This innovative design addresses the challenges of the complexity and low repeatability of the fabrication process and the high cost associated with microchip columns. Furthermore, its versatility makes it suitable for outdoor analysis applications.

Ultrafast Laser Processing of 2D Materials: Novel Routes to Advanced Devices.

Ultrafast laser processing has emerged as a versatile technique for modifying materials and introducing novel functionalities. Over the past decade, this method has demonstrated remarkable advantages in the manipulation of 2D layered materials, including synthesis, structuring, functionalization, and local patterning. Unlike continuous-wave and long-pulsed optical methods, ultrafast lasers offer a solution for thermal heating issues. Nonlinear interactions between ultrafast laser pulses and the atomic lattice of 2D materials substantially influence their chemical and physical properties. This paper highlights the transformative role of ultrafast laser pulses in maskless green technology, enabling subtractive, and additive processes that unveil ways for advanced devices. Utilizing the synergetic effect between the energy states within the atomic layers and ultrafast laser irradiation, it is feasible to achieve unprecedented resolutions down to several nanometers. Recent advancements are discussed in functionalization, doping, atomic reconstruction, phase transformation, and 2D and 3D micro- and nanopatterning. A forward-looking perspective on a wide array of applications of 2D materials, along with device fabrication featuring novel physical and chemical properties through direct ultrafast laser writing, is also provided.

A comparative study of surfactant-treated natural latex foam morphology, thermodynamic relationships and energy absorption: Talalay vs. dunlop processing

This study investigates the relationships between the morphology, energy absorption, and thermodynamic parameters of natural latex foams (NLFs) processed by the Dunlop and in-house Talalay methods, using different surfactant blends. Both methods involved mixing, moulding, and heating; the additional steps for the Talalay method involved cooling and gelation, a gel-freezing technique wherein the frozen foam is exposed to CO2 gas, inducing its transformation into a gel. The morphology of the internal structure of the NLFs was studied using 2D scanning electron micrographs and 3D micro- computerised tomography images. Two different surfactants, potassium laurate and pluronic, were used. Adding the blended surfactants reduced the porosity and increased the foam density of the NLF samples, improving mechanical properties. The cell size distribution of the NLF samples prepared using the Talalay method was broader than that of those prepared using the Dunlop method. In terms of the mechanical properties and energy absorption capabilities, the Talalay process resulted in samples with 20% lower compressive strength and 7% lower energy absorption than the control sample. A power-law relationship between the energy absorption per unit volume and the compression speed of the different foam samples was also observed. The ratio of the internal energy to the total compression force of the NLF samples prepared using the Talalay process was also lower than those prepared using the Dunlop process. The empirical insights derived from this study show how the mechanical properties and process technology associated with the producing of material foams could be improved.

Additively manufactured 3D micro scarf adhesive joints

AbstractHybrid manufacturing enables to overcome additive manufacturing (AM) constraints regarding the maximum feasible part dimension and/or complexity through part separation and subsequent adhesive joining of AM sub-parts. To ensure structural integrity of the joint at a minimum use of substrate volume, the AM inherent freedom of design can be exploited by realizing 3D micro scarf adhesive joints. The performance of this novel adhesive joint design was assessed by conducting optical measurements and static tensile tests using samples fabricated by laser-based powder bed fusion of metals (PBF-LB/M).

A multiscale experimental study of CFRP-UHPFRC interfacial bond behaviour: Failure mechanisms and a fibre volume dependent bond-slip law

Carbon fiber reinforced polymer (CFRP) materials are being increasingly used with ultra high performance fiber reinforced concrete (UHPFRC) to construct composite structural members making use of their unique properties. As the interfacial bond behaviour between CFRP and UHPFRC plays a key role in the design of such members, it was investigated in detail by multiscale experiments of single shear pull-off tests of 26 CFRP-UHPFRC bonded joints with different bond lengths and widths of CFRP laminates and 0.5–4% volume fraction (Vsf) of straight high-strength steel fibers (length = 13 mm, diameter = 0.2 mm). 12 CFRP-normal strength concrete (NSC) bonded joints were also tested for comparison. The surface strain evolution and the interfacial debonding process were captured and analysed by the digital image correlation (DIC). The complex microscale failure mechanisms, such as the mortar cracking, the CFRP-UHPFRC interfacial debonding, and the steel fibers’ slipping and pulling out of the mortar, were visualised and analysed by the 3D micro X-ray Computed Tomography (μXCT) scanning. It was found that the debonded layer of mortar under the laminates was much thinner than that in the CFRP-NSC bonded joints, due to the lack of coarse aggregates in UHPFRC. The peak pulling forces for the specimens with Vsf = 0.5%, 1%, 2%, and 4% were 9%, 21%, 28%, and 29% higher than those without steel fibers, respectively. An empirical bond strength model and an interfacial bond-slip model were proposed based on the test results, accounting for Vsf, the material properties, and the laminate to UHPFRC width ratio. Finally, the proposed bond-slip model was applied in finite element modelling to simulate the flexural behaviour of an FRP-UHPFRC composite deck in the literature, with the interfacial debonding failure and the ultimate loads successfully predicted.

Abstract 6396: Ex vivo 3D micro tumor testing to assess chemotherapy and immunotherapy responses for NSCLC patients

Abstract Background: Systemic treatment options for NSCLC patients consists of chemo-, targeted or immunotherapy. Although predictive biomarkers can guide treatment decisions, response prediction for chemo- and immunotherapy is still a challenge. Recent studies showed the potential of functional testing to assess patient sensitivity to drugs in various cancers, but NSCLC is lacking. This study reports the feasibility of ex vivo 3D micro lung tumor testing with native tumor microenvironment (TME) to enable treatment sensitivity profiling for all drug classes in parallel. Methods: Fresh NSCLC tumor tissue was collected from pleural fluid stage IVa/b (N=24) or resected primary tumor for stage I-III disease (N=11). Tumor clusters were isolated and exposed to drugs, while preserving the TME. Thirteen therapies were included, including cisplatin, pembrolizumab, osimertinib, and positive control for immune sensitivity (SEA). Morphological features were extracted from high-throughput 3D imaging data. Chemo- and targeted therapy sensitivity was based on AUC comparison of fitted dose-response curves. Immunotherapy sensitivity was classified on percentage and statistical significance of tumor killing, immune cell proliferation and cytokine profiling. Results: The overall assay success rate for solid samples was 64% (7/11), with 100% (4/4) success after protocol optimization. For pleural fluids, the overall success rate was 33% (8/24), caused by many samples arriving without tumor content (13/24, 54%). Excluding these samples, a technical success rate of 73% (8/11) was obtained. The assay was robust and reproducible (mean Z’ = 0.38, CV = 16.1%). Results were delivered in two weeks and on average, eight treatments were tested in parallel per sample. Patient-specific response profiles were observed for chemo-, targeted and immunotherapy. General immunotherapy sensitivity (SEA) was measured in 50% (6/12) of the tissues. Distinct responses were observed for the different immunotherapies: 33% (4/12), 17% (2/12) and 8% (1/12) of the patients responded to pembrolizumab, atezolizumab and/or ipilimumab, respectively. Strong response to osimertinib was observed in a patient with EGFR exon 19 mutation (AUC = 0.26) versus resistance in a WT patient (AUC=0.92). Conclusion: Ex vivo 3D micro tumor testing using liquid and solid tissues is feasible for NSCLC patients with resected primary tumor or pleuritis carcinomatosa. Distinct patient sensitivity profiles for chemo-, targeted and immunotherapies were measured. A preliminary correlation of targeted therapy response with mutation status was found. Discussion: The ex vivo 3D micro tumor testing platform is proven predictive for platinum-based therapy. The current study established the methods to accurately measure ex vivo NSCLC responses to all drug classes to correlate with clinical measures and further validate the platform for guiding treatment decisions. Citation Format: Esmee Koedoot, Timothy J. Sijsenaar, Lieke J. Ceton, Dieudonné J. van der Meer, Thomas J. van Brakel, Peter van Zwam, Erica Geraedts, Willemijn Vader, Egbert F. Smit, Laurie C. Steinbusch, Christi M. Steendam. Ex vivo 3D micro tumor testing to assess chemotherapy and immunotherapy responses for NSCLC patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6396.

Abstract 3726: Absence of synergistic effects for PARPi and immunotherapy combinations in ex vivo 3D micro tumor assay for ovarian cancer patients

Abstract Introduction: 50% of ovarian cancers are homologous recombination deficient (HRD), with 15% of the patients carrying a BRCA mutation. PARP inhibitors (PARPi) are designed to improve survival in HRD patients, but clinical responses to PARPi often do not match HRD status. In this study, a 3D ex vivo tumor testing platform was applied to quantify patient-specific drug responses to (combinations of) PARPi, chemo- and immunotherapies. Material and Methods: 81 patients with ovarian cancer eligible for chemotherapy were included in the trial between 2019 and 2022 in the Netherlands (IRB P18.032). Tumor clusters were isolated from ascites and solid tissue, seeded and exposed to three PARPi, standard-of-care chemotherapies and immunotherapies, both single agent and in combination. Ex vivo drug sensitivity was quantified using high-throughput 3D imaging and extraction of morphological features. Bliss scores were calculated for synergy analysis. Results: Results were generated in two weeks after sample collection. Ex vivo patient-specific response profiles were observed for all drug classes, with a small percentage of patients (7%) showing strong PARPi sensitivity reflected by strong tumor cluster shrinkage upon treatment. Significant correlation of drug sensitivity profiles was observed comparing the different PARPi between themselves, but also comparing PARPi and platinum responses. Interestingly, ex vivo sensitivity to olaparib and immunotherapy combinations demonstrated additive, but no synergistic effects (21 patients, 79 tests). In addition, olaparib responses were shown to be independent of immune responses (SEA). Conclusion: This study applied a predictive ex vivo 3D micro tumor testing platform to classify patient-specific sensitivity to (a combination of) PARPi, chemo- and immunotherapies in over 80 patients. The current dataset demonstrates the potential of ex vivo testing to identify patients that are responsive to PARPi. No synergistic effects were observed for these drugs in combination with immunotherapies. Discussion: Evaluation of PARPi responses in a functional 3D micro tumor assay could support identification of responsive patients prior to treatment. Distinct responses were observed for PARPi and immunotherapies. No synergistic but additive effects were measured, suggesting that ovarian cancer patients could benefit from PARPi and immunotherapies. Correlation of clinical and ex vivo drug responses to PARPi in combination with available HRD tests will further validate the platform for predicting patient clinical outcome. Citation Format: Lieke J. Ceton, Esmee Koedoot, Timothy J. Sijsenaar, Dieudonné J. van der Meer, Marta Montero Garcia, Jurrian van der Valk, Kristofer Maad, Cor de Kroon, Anne van Altena, Willemijn Vader, Judith Kroep, Nelleke Ottevanger. Absence of synergistic effects for PARPi and immunotherapy combinations in ex vivo 3D micro tumor assay for ovarian cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3726.