THE IJM NANOSCALER: A BENCHTOP SYSTEM FOR LIPID NANOPARTICLE FORMULATION

IJM NANOSCALER: 脂質(zhì)納米顆粒配方的臺式系統(tǒng)

KNAUER's new benchtop IJM NanoScaler system is designed for lab-scale lipid nanoparticle formu-lation – allowing scientists to screen for optimal process parameters to formulate API-containing lipid nanoparticles.

KNAUER的新型臺式IJM NanoScaler系統(tǒng)是為實(shí)驗(yàn)室規(guī)模的脂質(zhì)納米顆粒配方設(shè)計(jì)的，允許科學(xué)家篩選的工藝參數(shù)，以制備含API的脂質(zhì)納米顆粒。

The IJM NanoScaler is made for research and de-velopment as well as pre-clinical and small-scale production of lipid nanoparticles. Equipped with our lipid nanoparticle producing Impingement Jets Mixing (IJM) technology the NanoScaler allows researchers to optimize encapsulation conditions for their API-based therapy before scaling up the process to run on a larger IJM NanoProducer unit.

IJM NanoScaler用于脂質(zhì)納米顆粒的研究和開發(fā)以及臨床前和小規(guī)模生產(chǎn)。配備了我們的脂質(zhì)納米顆粒產(chǎn)生沖擊射流混合(IJM)技術(shù)，納米縮放器允許研究人員優(yōu)化基于API的治療的封裝條件，然后將工藝擴(kuò)大到更大的IJM NanoProducer單元。

The NanoScaler is made for low sample con-sumption so as not to waste valuable API. Its small footprint means it can comfortably sit on the benchtop of a research and development lab. The system comes with five different KNAUER Impinge-ment Jets Mixers to help researchers determine which conditions result in the optimum level of API encapsulation. These active pharmaceutical ingredients include complex or delicate API like RNA, mRNA, siRNA, and DNA-based molecules, or products that need specific entry into target cells. In addition researchers can use their own custom mixing unit and benefit from the flexibility of the system set-up. The formulation process can be remotely controlled by software; ran from a conventional PC or laptop, or even a tablet.

NanoScaler是為低樣品消耗而制造的，從而不浪費(fèi)有價值的API。它占地面積小，可以舒適地坐在研發(fā)實(shí)驗(yàn)室的工作臺上。該系統(tǒng)配備了五種不同的KNAUER撞擊射流混合器，以幫助研究人員確定哪種條件可以產(chǎn)生API封裝的水平。這些活性藥物成分包括復(fù)雜或精細(xì)的API，如RNA、mRNA、siRNA和基于DNA的分子，或需要特定進(jìn)入靶細(xì)胞的產(chǎn)品。此外，研究人員可以使用自己的定制混合單元，并從系統(tǒng)設(shè)置的靈活性中受益。配方過程可通過軟件遠(yuǎn)程控制;從傳統(tǒng)的個人電腦或筆記本電腦，甚至平板電腦上運(yùn)行。

Key parameters

PDI: between 0.1 and 0.2

Particle size:80–90 nm

Encapsulation Efficiency > 90 %

關(guān)鍵參數(shù)

PDI:在0.1到0.2之間

粒度:80 - 90nm

封裝效率> 90%

LNP FORMULATIONS FOR PRE-CLINICAL RESEARCH AND PRODUCTION

用于臨床前研究和生產(chǎn)的LNP配方

The NanoScaler can be used to produce lipid-encapsulated nucleotides at a range from 1 ml to hundreds of milliliters meaning the system is perfect for:

NanoScaler可以用于生產(chǎn)1毫升到數(shù)百毫升的脂包核苷酸，這意味著該系統(tǒng)是的:

Proof of concept testing and process optimization – pure nucleotides are an expensive resource. Carry out proof of concept testing and process optimization at the 1,000 μl scale to avoid wastage.

概念驗(yàn)證測試和工藝優(yōu)化-純核苷酸是一種昂貴的資源。在1000 μl范圍內(nèi)進(jìn)行概念驗(yàn)證測試和工藝優(yōu)化，以避免浪費(fèi)。

Pre-clinical trials – Pre-clinical testing can be carried out using 100 ml of nucleotides such as, for in vitro studies to determine the tolerability, efficacy and potential toxicity of the mRNA therapy of interest.

臨床前試驗(yàn)-可使用100毫升核苷酸進(jìn)行臨床前試驗(yàn)，用于體外研究，以確定感興趣的mRNA治療的耐受性、療效和潛在毒性。

Small scale production – Once proof-of-concept and safety testing have been successfully conducted, production of LNP encapsulated API′s can even be carried out at up to 0.1 Liter per minute with the IJM NanoScaler or using KNAUER’s scaled-up IJM-NanoProducer Units.

小規(guī)模生產(chǎn)一旦概念驗(yàn)證和安全測試成功進(jìn)行，LNP封裝API的生產(chǎn)甚至可以以每分鐘0.1升的速度進(jìn)行，使用IJMNanoScaler或使用KNAUER的放大IJM-NanoProducer單元。

Which formulation parameters can be tested using the NanoScaler?

The IJM NanoScaler enables the scouting of several key process parameters during the lipid nanoparticle encapsulation stage.

哪些配方參數(shù)可以用NanoScaler測試?

IJMNanoScaler能夠在脂質(zhì)納米顆粒封裝階段探測幾個關(guān)鍵的工藝參數(shù)。

Mixing unit – The five different Impingement Jets Mixer geometries, plus the opportunity to integrate a custom mixing unit, allow determination of the process conditions required to achieve maximum efficiency, optimal particle size and homogeneous size distribution.

混合單元-五種不同的沖擊射流混合器幾何形狀，加上集成自定義混合單元的機(jī)會，允許確定所需的工藝條件，以實(shí)現(xiàn)率，粒度和均勻的粒度分布。

Mixing flow rate and ratio – Determine how the specific physicochemical properties of the lipid nanoparticle are impacted by the mixing flow – find out which flow rates and ratio provide optimum lipid nanoparticle encapsulation.

混合流量和比例-確定脂質(zhì)納米顆粒的具體物理化學(xué)性質(zhì)如何受到混合流量的影響-找出哪個流量和比例能提供的脂質(zhì)納米顆粒封裝。

Lipid formulation – Testing of new lipid formulations, for example lipids with embedded antibodies for targeted medicines, is possible using the NanoScaler. Determine the conditions required to ensure lipid nanoparticle encapsulation takes place before producing the therapy at scale for trials.

脂質(zhì)配方——測試新的脂質(zhì)配方，例如含有靶向藥物抗體的脂質(zhì)配方，可以使用NanoScaler。確定所需的條件，以確保脂質(zhì)納米顆粒包封，然后進(jìn)行大規(guī)模生產(chǎn)治療試驗(yàn)。

Dilution protocols – The liquid flow path of the NanoScaler can be configured to either include or bypass the dilution step following lipid nanoparticle formation – allowing scientists to produce formulations at the exact concentration required.

稀釋方案——NanoScaler的液體流動路徑可以配置為包括或繞過脂質(zhì)納米顆粒形成后的稀釋步驟——使科學(xué)家能夠在所需的精確濃度下生產(chǎn)配方。

Number of impingement jets mixers: 5, IJM 1-5 manual selection

Number of pumps:3

Number of flow meters:on request

Number of valves:2

Process connection inlet**:1/8" OD, 2.1 mm ID FEP tubing (UNF 1/4-28 thread, flat bottom)

Process connection outlet**:1/16" OD, 0.5 mm ID PEEK tubing (UNF 10-32, thread coned)

Volumetric flow rate:up to 0.1 l/min

Volumetric flow rate:up to 6 l/h

Maximum operating pressure***:140 bar (2030 psi)

Liquid temperature range:4–60 °C (39.2–140 °F)

Wetted materials:stainless steel, PEEK, titanium, FFKM, PTFE (GFP 55), aluminum oxide, ruby, sapphire, ETFE, PETP, zirconium oxide, Hastelloy, FEP

Software:CDS optional available 21 CFR part 11 and Gamp 5 compliant

Interfaces:LAN, pin header connectors

Power supply:docking station (including pumps and valves): 100–240 VAC single phase, 50/60 Hz; PC: 100–240 VAC single phase, 50/60 Hz; Monitor: 100–240 VAC single phase, 50/60 Hz; Network switch: 100-240 VAC single phase, 50/60 Hz, 12V DC Power supply

Power consumption (per device):docking station (including pumps and valves): maximum 130 W; PC: 1000 W; monitor: 380 W; network switch: 50 W

Ambient conditions:temperature range: 4–40 °C; 39.2?104 °F; below 90 % humidity (non-condensing)

Dimensions (W x H x D):361 x 501 x 603 mm

Net weight (approx.):35 kg

API-predilution and quenching:only quenching

Customized technical documentation, order-ａnd article-related:on request

Factory acceptance test:on request

Site acceptance test:on request

撞擊射流混合器數(shù)量:5個，IJM 1-5手動選擇

泵的數(shù)量:3

流量計(jì)數(shù)量:按要求提供

閥門數(shù)量:2

工藝連接入口**:1/8"外徑，2.1 mm ID FEP管(UNF 1/4-28螺紋，平底)

工藝連接出口**:1/16" OD, 0.5 mm ID PEEK管(UNF 10-32，螺紋錐形)

體積流量:可達(dá)0.1升/分鐘

容積流速:高達(dá)6升/小時

工作壓力***:140 bar (2030 psi)

液體溫度范圍:4-60°C(39.2-140°F)

濕化材料:不銹鋼，PEEK，鈦，F(xiàn)FKM, PTFE (GFP 55)，氧化鋁，紅寶石，藍(lán)寶石，ETFE, PETP，氧化鋯，哈氏合金，F(xiàn)EP

軟件:可選的cd 21 CFR part 11和Gamp 5兼容

接口:局域網(wǎng)，引腳頭連接器

電源:對接站(包括泵和閥門):100-240伏單相，50/60赫茲;PC: 100-240伏單相，50/60赫茲;顯示器:100-240伏單相，50/60赫茲;網(wǎng)絡(luò)開關(guān):100-240伏單相，50/ 60hz, 12V DC電源

功率消耗(每臺設(shè)備):對接站(包括泵和閥門):130w;電腦:1000 W;監(jiān)控:380 W;網(wǎng)絡(luò)交換機(jī):50w

環(huán)境條件:溫度范圍:4-40°C;39.2?104°F;濕度低于90%(不凝結(jié))

尺寸(寬×高×深):361 × 501 × 603毫米

凈重(約):35公斤

API預(yù)稀釋淬火:僅淬火

定制技術(shù)文檔，與訂單和產(chǎn)品相關(guān):按需提供

工廠驗(yàn)收測試:按要求進(jìn)行

現(xiàn)場驗(yàn)收試驗(yàn):按要求進(jìn)行