Periodic Reporting for period 1 - KIDNEW (breakthrough technologies for an implantable artificial kidney)
Reporting period: 2023-05-01 to 2024-04-30
The KIDNEW project aims to develop groundbreaking and modular technology to enable an implantable artificial kidney with better functional kidney replacement therapy than currently available, without need for immunosuppressive drugs and at reduced costs. It provides three breakthrough technologies:
1. Silicon-based hemofilter with a hemocompatible coating
2. Kidney tubule cell unit for waste secretion and reabsorption of water and useful solutes
3. A multichip model with stacked integrated filter-tubule units
Key achievements include the development of silicon nanopore membranes with promising mechanical strength, hemocompatible anti-fouling coatings using PEG-based polymer brushes, a kidney tubular cell unit using silicon substrates, and a photonic sensor for inline monitoring of toxins compatible with the expected effluent rates of the system. Bioimpedance-based monolayer integrity monitoring was explored but needs improvement in sensitivity. Several advanced test benches were developed for rapid in vitro validation of the silicon membranes, including measurement cells for porometry tests and a miniaturized flow and pressure test platform for testing porosity, hydraulic permeance, and sieving coefficients. An advisory board was installed and a stakeholder workshop was held and a website was launched and multiple dissemination activities were undertaken.
1. Silicon-based hemofilter with a hemocompatible coating
2. Kidney tubule cell unit for waste secretion and reabsorption of water and useful solutes
3. A multichip model with stacked integrated filter-tubule units
Key achievements include the development of silicon nanopore membranes with promising mechanical strength, hemocompatible anti-fouling coatings using PEG-based polymer brushes, a kidney tubular cell unit using silicon substrates, and a photonic sensor for inline monitoring of toxins compatible with the expected effluent rates of the system. Bioimpedance-based monolayer integrity monitoring was explored but needs improvement in sensitivity. Several advanced test benches were developed for rapid in vitro validation of the silicon membranes, including measurement cells for porometry tests and a miniaturized flow and pressure test platform for testing porosity, hydraulic permeance, and sieving coefficients. An advisory board was installed and a stakeholder workshop was held and a website was launched and multiple dissemination activities were undertaken.
WP1
The seven partners contributed to timely fulfillment of the deliverables during the first year of the project. The KIDNEW consortium had a successful kickoff meeting in Sept ’23. A consortium agreement was arranged and a project handbook (D1.1) and data management plan (D1.2) were compiled. An advisory board was installed.
WP2
IMEC BE has achieved the following in M1-12:
- Development of nanoporous Si membrane structure with high aspect ratio (5:1)
- Uniform monodisperse 20 nm pores at 200 mm wafer level
- A full process to release the Si membranes using a backside fluidic cavity.
ME-SEP developed special measurement cells for the Poroliq (liquid-liquid porometer) to allow porometry measurements of the SNMs. Since SNMs were not available in sufficient size yet, porous Anodic Aluminum Oxide Anisotropic (AOO) membranes were used for testing which is currently ongoing.
CNRS, in charge of developing hemocompatible coatings ensuring non-fouling of the blood filtration membranes, has set up the chemistry protocols for the design of PEG-based polymer brushes.
With regard to the BAK-Photosensor, the boundary conditions for the input flow range and the input pressure from the bioartificial kidney (BAK) unit were defined determining the specifications for a BAK-Photosensor interface. The BAK-Photosensor interface facilitates the BAK unit integration with the photonic sensor for monitoring continuous elimination of the filtered-out waste products-uremic toxins. A schematics of the BAK-Photonic interface was prepared. Technical realization of the BAK-Photosensor interface hardware was initiated, containing development of the RO degassing system, heater and a hydraulic scheme, design and testing of the electronics on the circuit board for a microcontroller-based software.
WP3
IMEC BE has achieved the following specifications for partner testing in M1 -M12;
- Frontside patterning of 6 um diameter pores
- Backside patterning of curved Si, with 400 um diameter
Different renal epithelial cell types (conditionally immortalized proximal tubule cells (ciPTECs) and tubular cells derived from adult stem cell (ASC)-derived kidney tubule organoids (tubuloids)) were found to be compatible with the Si-waiver base material via different coating strategies.
Bio-impedance measurements were performed by IMEC-NL at the UU using both CaCo2- and ciPTECs. Taken together, the results indicate that there is a minor difference in resistance due to the presence of a ciPTEC monolayer. Disruption of the cell monolayer was induced using chemical, mechanical and temperature stimuli.
WP4
A miniaturized flow and pressure test platform was realized at UMCU comprising an in-house developed small scale test setup to characterize the strength, fluidic flux, pore size distribution and sieving coefficient of silicon nanofiltration membranes. Two batches of silicon membranes were tested with significant improvements in quality of the second batch, although porosity, hydraulic permeance, pore-size and hydrophilicity need further optimization
WP5
A website was launched and continuously updated with the publications, results and conferences within KIDNEW (D5.1). The CDE-plan was written together with all partners (D5.2). On the 3rd of April 2024, a stakeholder workshop was held at Holst Center. A report on this stakeholder workshop was written (D5.3).
The seven partners contributed to timely fulfillment of the deliverables during the first year of the project. The KIDNEW consortium had a successful kickoff meeting in Sept ’23. A consortium agreement was arranged and a project handbook (D1.1) and data management plan (D1.2) were compiled. An advisory board was installed.
WP2
IMEC BE has achieved the following in M1-12:
- Development of nanoporous Si membrane structure with high aspect ratio (5:1)
- Uniform monodisperse 20 nm pores at 200 mm wafer level
- A full process to release the Si membranes using a backside fluidic cavity.
ME-SEP developed special measurement cells for the Poroliq (liquid-liquid porometer) to allow porometry measurements of the SNMs. Since SNMs were not available in sufficient size yet, porous Anodic Aluminum Oxide Anisotropic (AOO) membranes were used for testing which is currently ongoing.
CNRS, in charge of developing hemocompatible coatings ensuring non-fouling of the blood filtration membranes, has set up the chemistry protocols for the design of PEG-based polymer brushes.
With regard to the BAK-Photosensor, the boundary conditions for the input flow range and the input pressure from the bioartificial kidney (BAK) unit were defined determining the specifications for a BAK-Photosensor interface. The BAK-Photosensor interface facilitates the BAK unit integration with the photonic sensor for monitoring continuous elimination of the filtered-out waste products-uremic toxins. A schematics of the BAK-Photonic interface was prepared. Technical realization of the BAK-Photosensor interface hardware was initiated, containing development of the RO degassing system, heater and a hydraulic scheme, design and testing of the electronics on the circuit board for a microcontroller-based software.
WP3
IMEC BE has achieved the following specifications for partner testing in M1 -M12;
- Frontside patterning of 6 um diameter pores
- Backside patterning of curved Si, with 400 um diameter
Different renal epithelial cell types (conditionally immortalized proximal tubule cells (ciPTECs) and tubular cells derived from adult stem cell (ASC)-derived kidney tubule organoids (tubuloids)) were found to be compatible with the Si-waiver base material via different coating strategies.
Bio-impedance measurements were performed by IMEC-NL at the UU using both CaCo2- and ciPTECs. Taken together, the results indicate that there is a minor difference in resistance due to the presence of a ciPTEC monolayer. Disruption of the cell monolayer was induced using chemical, mechanical and temperature stimuli.
WP4
A miniaturized flow and pressure test platform was realized at UMCU comprising an in-house developed small scale test setup to characterize the strength, fluidic flux, pore size distribution and sieving coefficient of silicon nanofiltration membranes. Two batches of silicon membranes were tested with significant improvements in quality of the second batch, although porosity, hydraulic permeance, pore-size and hydrophilicity need further optimization
WP5
A website was launched and continuously updated with the publications, results and conferences within KIDNEW (D5.1). The CDE-plan was written together with all partners (D5.2). On the 3rd of April 2024, a stakeholder workshop was held at Holst Center. A report on this stakeholder workshop was written (D5.3).
KIDNEW provides a proof of concept on three breakthrough innovations:
Solid-state miniature ultra-high flux silicon (Si)-based filter with a high-density of uniform nanopores through novel block copolymer self-assembly, and with novel hemocompatible biomimetic polymer brush coating connected to a photonic clotting monitoring sensor and (thrombolytic) cleansing tool;
Solid-state bioreactor-grown kidney tubule cell monolayers on novel biomimetic Si-wafer based membrane with bioimpedance based monolayer integrity monitoring and monolayer repair functionality using growth-factors;
Solid-state integrated functional biohybrid filter and tubule exchange units stacked in parallel in a multichip to demonstrate functional implantable KRT in goats.
Solid-state miniature ultra-high flux silicon (Si)-based filter with a high-density of uniform nanopores through novel block copolymer self-assembly, and with novel hemocompatible biomimetic polymer brush coating connected to a photonic clotting monitoring sensor and (thrombolytic) cleansing tool;
Solid-state bioreactor-grown kidney tubule cell monolayers on novel biomimetic Si-wafer based membrane with bioimpedance based monolayer integrity monitoring and monolayer repair functionality using growth-factors;
Solid-state integrated functional biohybrid filter and tubule exchange units stacked in parallel in a multichip to demonstrate functional implantable KRT in goats.