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22 KiB
Markdown
124 lines
22 KiB
Markdown
---
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type: "Reference"
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title: "Theme 1 · Organoid culture and equipment (CelVivo / 3Brain)"
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description: "Synthesis page for Robin's organoid culture and equipment theme — CelVivo ClinoStar/ClinoReactor for 3D suspension culture and 3Brain HD-MEA for neural/cardiac electrophysiology readout."
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tags: [theme, organoid, celvivo, 3brain, life-sciences]
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---
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# Theme 1 · Organoid culture and equipment (CelVivo / 3Brain)
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This is the synthesis page for **类器官培养与设备** — Robin's core product line combining 3D suspension culture vessels (CelVivo ClinoStar / ClinoReactor) with HD-MEA electrophysiology readout (3Brain BioCAM DupleX / Accura-3D / CorePlate).
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## What this theme covers
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- **Vendor portfolio:** CelVivo ApS (DK) and 3Brain AG (CH).
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- **Application domain:** MSC spheroids, patient-derived organoids (PDO), iPSC-derived brain / midbrain organoids (hMOs), assembloids, neural and cardiac electrophysiology.
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- **Workflow chain:** 3D culture (ClinoStar / ClinoReactor) → maturation (21–110 days) → functional readout (3Brain HD-MEA).
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- **Customer lane:** Chinese pharma R&D / CDMO / biotech + academic neuroscience (neural organoids).
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## Vendor product mapping
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| Vendor | Hardware | Function | SKU / identifier |
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| --- | --- | --- | --- |
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| CelVivo | **ClinoStar** (30003) | Multi-well rotating-wall 3D culture | `30003` |
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| CelVivo | **ClinoReactor** (10004-12 / 10005-6 demo kit) | Single-use bioreactor, long-term 21–110 day culture | `10004-12`, `10005-6` |
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| CelVivo | **SP5D-24W** low-adherence plate | Anti-adhesion consumable for ClinoReactor | `SP5D-24W` |
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| 3Brain | **BioCAM DupleX** | HD-MEA acquisition system (hMOs / brain organoids) | `BioCAM DupleX` |
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| 3Brain | **Accura-3D** HD-MEA chip (4096 electrodes) | 3D / organoid-compatible chip | `Accura-3D` |
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| 3Brain | **CorePlate** (1W / 6W load) | High-resolution functional readout for iPSC neurons, cardiac models, brain organoids, assembloids, 3D spheroids | `CorePlate` |
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| 3Brain | **Sample Holder Set / PressNet** (UK GB2624872) | Mechanical net-press for CorePlate, 250–1250 µN load | `Sample Holder Set` |
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| 3Brain | **BrainWave 5/6** software | Unified acquisition + analysis | `BrainWave 5/6` |
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## Workflow chain (CelVivo → 3Brain)
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```mermaid
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stateDiagram-v2
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[*] --> Seeding: iPSC / MSC / biopsy
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Seeding --> EB_Formation: Day 0-7 (ClinoReactor)
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EB_Formation --> Maturation: Day 7-21 (ClinoStar 20 RPM)
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Maturation --> LongTermCulture: Day 21-110 (ClinoReactor / ClinoStar)
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LongTermCulture --> FunctionalReadout: transplant to 3Brain Accura-3D (4096 electrodes)
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FunctionalReadout --> DrugScreen: BrainWave 5 / spike-train analysis
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DrugScreen --> [*]
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note right of LongTermCulture
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Bosnjakovic 2025: Day 21 mature HepG2 3D spheroid + PAH exposure
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Raji 2026: Week 12 hMOs TH+ 58%
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Groningen: Day 110 / 8 mm brain organoid
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end note
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note right of FunctionalReadout
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3Brain HD-MEA is the gold-standard electrophysiology
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readout for organoids (Raji 2026 + 3Brain vendor docs)
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end note
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```
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The state diagram shows the canonical CelVivo → 3Brain workflow: 3D suspension culture (ClinoReactor / ClinoStar) → maturation (21–110 days) → transplant to 3Brain HD-MEA → drug screening / disease modeling readout.
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## Vendor evidence anchors
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### CelVivo evidence
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- **Whitepaper: "Breaking the Bias" (2026, 16 pp)** — CelVivo's official vendor narrative on brain organoid long-term culture. Key data: ~110 day / 8 mm diameter brain organoid (Univ. Groningen, Trombetta-Lima); sc-RNA-seq 17,738 cells at Day 90 (Univ. Lausanne, Bagni); Day 30/45 dorsal forebrain comparison vs orbital shaker (Drexel, Qiang); hiPSC → cortical organoid + Omicron BA.5 (QIMR Berghofer, Stewart 2022). 4 patents: WO 2021/001472, WO 2021/245117, WO 2022/008292, WO 2022/144461. Full synthesis at [`/sources/literature-celvivo-brain-whitepaper-2026.md`](/sources/literature-celvivo-brain-whitepaper-2026.md).
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- **Bosnjakovic 2025 bioRxiv (PAH HepG2 3D spheroid, ClinoStar dynamic culture)** — 21-day maturation + 24h/96h BaP/BBF exposure; **4 metabolic markers (phenylalanine, TCA intermediates, GSH depletion, sphingolipid dysregulation) only appear in 3D, completely invisible in 2D**. Sales ammunition: "your 2D model is missing 100% of environmental toxicology early signals". Synthesis at [`/sources/literature-cel-bosnjakovic-2025-pah-deepread.md`](/sources/literature-cel-bosnjakovic-2025-pah-deepread.md).
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- **Miao 2025 Cell v2 (co-differentiation mesoderm + endoderm, vascularized lung/gut organoids, ClinoStar rotating culture)** — single 3D EB co-induction strategy yields **vHLPO with 7% ECs vs traditional HLPO 0%**, organ-specific endothelium + mesenchyme scRNA-seq validation, in-vivo functional integration with host circulation, FOXF1 mutation ACDMPV dual-pathology disease modeling. Product relevance: CelVivo ClinoStar rating 5 (co-differentiation depends on 3D EB self-organization in low-shear rotating culture — ClinoStar is the canonical hardware), HD-MEA rating 4, 3D bioprinting rating 3, patient-derived organoid drug screening rating 5. Synthesis at [`/sources/literature-miao-2025-cell-vascularization-v2-deepread.md`](/sources/literature-miao-2025-cell-vascularization-v2-deepread.md).
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- **Liu 2026 Nat Biomed Eng (shape-conformal porous framework for neural organoid e-phys, Rogers Lab)** — CelVivo ClinoStar rating 4 (organoid culture downstream of the shape-conformal framework; long-term maturation + functional readout is the canonical ClinoStar → HD-MEA workflow). Synthesis at [`/sources/literature-liu-2026-nbme-shape-conformal-organoid-deepread.md`](/sources/literature-liu-2026-nbme-shape-conformal-organoid-deepread.md). See 3Brain evidence for the HD-MEA read side.
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- **Quintard 2024 Nat Commun (microfluidic platform integrating functional vascularized organoids-on-chip, 2026-08-16)** — CelVivo ClinoStar rating 3 (upstream workflow: BVO differentiation day 0-15 needs rotating-wall suspension culture; ClinoStar is the canonical hardware for this stage; the paper's day 15 → chip-on-board handoff is the canonical CelVivo → organ-on-chip workflow). Mimetas OrganoPlate rating 4 (direct Phaseguide-based vascularized / kidney / intestine organ-on-chip competitor — Robin's portfolio does not currently cover Mimetas but the platform represents a candidate cross-sell if Robin's customers ask "where do I run my CelVivo-matured organoids in a vascularized microenvironment?"). Emulate Organ-Chip rating 3 (Colon-Intestine-Liver platform companion). 10 通道并行微流控芯片 + hiPSC-BVO + 间充质球体 + 胰岛球体 + 肺类器官 跨类器官验证; 血管层级化 37 µm 上游动脉-静脉 + 8 µm BVO 毛细管; 壁剪切 27-2000 s⁻¹ 完美匹配人体毛细血管生理范围 50-1900 s⁻¹. 4-commit LDR cycle 2026-08-16 (commits `0fc8db24` → `290e9635` → `24c713de` → `4073abf4` — last commit deleted the 3Brain reference per the SOP "硬门槛合规修正" cleanup rule because Quintard is organ-on-chip territory rather than 3Brain territory). Wiki IDs 1719/1720/1722, NocoDB Id 3297, DOI 10.1038/s41467-024-45710-4. Sales ammunition: "你的类器官前段培养到 day 15, 后段血管化怎么接? 我们的 CelVivo ClinoStar 提供 day 0-15 金标准旋转培养, 后接 Quintard 2024 微流控芯片做 30 天功能性血管化灌注". Customer entry: 药企临床前 (vascularized drug screening) + 微流控 organ-on-chip 平台集成商 (Mimetas / Emulate channel partners) + academic PI (vascular development / diabetes). Vault path: `obsidian-vault/Literature/Deep-Reads/Organoid/quintard_2024_vasorganoid_chip.md` (189 lines + 6 真图).
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- **Liang 2026 Sci Rep (mouse liver organoid 3-轨道 + fibrosis modeling, 2026-08-12)** — CelVivo ClinoStar rating 4 (P1-P10 长程扩增对应旋转培养 30+ 天无剪切; single DAPT only sustains P5, DAPT+Dex 协同才实现 P10 稳定成熟), CelVivo ClinoReactor rating 4 (单组织 3 轨道 [Hep/Cho/HSC] 分通道灌流; TGFβ 时间程序精确切换实现纤维化激活模型), CelVivo PhaseHolographic 成像 rating 3 (3D 球体直径/CV 实时 QC), 3Brain HD-MEA rating 3 (肝-神经互作延伸场景). 3 轨道 from 单份小鼠肝组织 (密度梯度离心 + 差速贴壁) → DAPT+Dex P1-P10 长程稳定成熟 (ALB / PAS / LDL / CYP 跨代保持) → TGFβ 5-7 天激活 qHSC → aHSC (Acta2/Col1a1 上调) → aHSC 共培养诱导 Hep-Orgs EMT (Snail/Twist/Vimentin ↑; ALB/CK8 ↓; Lgr5/EpCAM ↓; Ki67 ↓) = 体外肝纤维化模型. Wiki.js Id=1716, NocoDB Id=770, PMID 41857098. Page 946 9 项 SOP 重写版 + page 934 修齐 标杆 (4-commit LDR cycle 2026-08-12). **First deep-read whose `related:` field already names `[[MOC-类器官与3D培养]]`** on the day of publication — confirms MOC pattern in active use on real deep-reads. Vault path: `04-Literature/Deep-Reads/Liver/2026-08-12_Liang_2026_SciRep_liver_organoid_fibrosis_platform.md` (170 lines). Sales ammunition: "你的肝类器官只能短期培养? DAPT+Dex P1-P10 稳定成熟 + 单组织 3 轨道 + 14 天纤维化模型 — ClinoStar + ClinoReactor 一站搞定". Customer entry: 药企临床前 (抗纤维化药筛 14+ 天 3D 多细胞模型) + 临床肝活检中心 (1-2 mg 组织 → 3 周药敏 → ClinoReactor 6 通道一次测 6 药). Tracks in `/commitments.md` as `liang-2026-celvivo-clinostar-positioning`.
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- **Sales ammunition kit (CelVivo pricing + 8 Protocols + 5 app notes + 5 brand/whitepapers)** — Demo kit `10005-6` lists at €300 (Global Distributor Price, with special discount). 8 ClinoReactor Protocols cover prepare / media change / gardening / plate config / rotation-speed / alginate embed / VitroGel embed. 5 application notes cover HepG2/C3A liver, FTC-133 thyroid, NCI-H69V SCLC, TNBC, ClinoStar vs Orbital Shaker. Synthesis at [`/sources/sales-ammunition.md`](/sources/sales-ammunition.md).
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- **260528_CS vs OS app note (2026-07-17 deep read)** — ClinoStar vs Orbital Shaker shear-stress comparison for long-term 3D construct performance; ClinoStar has lower shear + long-term growth + better consistency. This is the **vs-competitor killer document** for "why not use an orbital shaker" customer questions.
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- **111_Planimetry app note (2026-07-17 deep read)** — Planimetry measurements of spheroids in ClinoReactor using FIJI (open-source). Standard answer for "how to quantify spheroids".
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### 3Brain evidence
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- **Raji 2026 Mol Psychiatry (hMOs + 3Brain HD-MEA, 2026-07-27 deep read)** — WNT-modulated human midbrain organoids + 3Brain BioCAM DupleX + Accura-3D (4096 electrodes) + BrainWave 5. **TH+ 58% at 12 weeks** (vs 2D 18%, 3D static 32%). DA release 76 pg/mL (vs 2D 12, 3D static 28). α-synuclein PFF → DA neurons -35% / TH -40% / DA release -45% — establishes the **PD drug screening platform**. Shear-stress 15x lower than orbital shaking (0.13 dyn/cm² vs 2.03 dyn/cm²). Synthesis at [`/sources/literature-raji-2026-deepread.md`](/sources/literature-raji-2026-deepread.md).
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- **Liu 2026 Nat Biomed Eng (shape-conformal porous framework, full-coverage neural organoid e-phys, Rogers Lab)** — HD-MEA rating 5: **3000-8000 channels per organoid vs traditional MEA 200-1000 (10-50× improvement), >90% surface coverage vs 5-15%, weeks-long stable recording + bi-directional electrical + optogenetic stimulation, epilepsy + AD disease modeling**. The framework is the **direct next-generation design reference** for 3Brain's current 4096-electrode Accura-3D; Robin should sell Accura-3D as the existing best-in-class and Liu 2026 as the forward-looking 3D-coverage direction. Synthesis at [`/sources/literature-liu-2026-nbme-shape-conformal-organoid-deepread.md`](/sources/literature-liu-2026-nbme-shape-conformal-organoid-deepread.md). Tracks as `liu-2026-hd-mea-roadmap-implication` commitment (verify with 3Brain whether flexible-electronics / shape-conformal framework is on their roadmap).
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- **Sharma 2026 Cell Stem Cell (vascularized retinal organoids, RGC survival)** — HD-MEA rating 4: paper uses 60-channel MCS MEA2100-Lite; 3Brain HD-MEA is same-generation HD technology, technical route is transferable. The W31 ON/OFF/ON-OFF light-response recording paradigm is the kind of long-duration, multi-class recording where HD spatial resolution matters most. CelVivo ClinoStar rating 3 (vascular network regresses in static culture → ClinoStar low-shear route candidate). W18 RGC yield **18.2% vs ctrl-RO 1.21% (15× improvement)** through C3 endothelial monolayer integration. Synthesis at [`/sources/literature-sharma-2026-cell-stem-cell-vascularized-retinal-organoid-rgc-deepread.md`](/sources/literature-sharma-2026-cell-stem-cell-vascularized-retinal-organoid-rgc-deepread.md).
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- **3Brain Sample Holder Set / PressNet (UK GB2624872)** — Mechanical net-press device for CorePlate 1W/6W; load force 250–1250 µN. Recorded 2026-07-07 (untracked in vault). Carryover evidence in [`/sources/git-repo.md`](/sources/git-repo.md) Notable entities.
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- **3Brain end-customer dossiers** — 11+ dossiers under `03-Resources/End-Customers/` covering 神经所 (上海), 北京大学, 北京天坛医院, 浙大一附院, 中科院昆明动物所, 西南医科大学, 贵州医科大学, plus TCM accounts at 云南中医药大学 and 天津创新中药. Listed in [`/sources/git-repo.md`](/sources/git-repo.md) Notable entities.
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- **Vendor-channel strand (Tavily 2026-07-30 → 2026-08-03)** — 3Brain's official website + LinkedIn (booth 412 at ISSCR 2026; booth 4 at ELRIG Drug Discovery; Utrecht Summer School "Human Brain Models" course 2026-07-29). Tracks in `/commitments.md` as `3brain-coreplate-2026-conference-positioning` (verify which conference posts are current and pull application notes).
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## Cross-vendor workflow links
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- **CelVivo + 3Brain joint workflow** (from Raji 2026): hMOs are cultured in a **bioreactor** (CelVivo-class, low-shear rotating-wall) for 12 weeks; transplanted to **3Brain Accura-3D** (4096-electrode HD-MEA chip) for 24h spike-train recording via BrainWave 5. Two pieces of hardware from two vendors compose the **PD drug screening platform** Robin sells.
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- **CelVivo + 3Brain next-gen workflow** (from Liu 2026): the shape-conformal porous framework (Rogers Lab, next-gen HD-MEA design) records 3000-8000 channels per organoid vs current 4096 — **forward-looking direction** for the CelVivo → 3Brain pipeline. Track in `/commitments.md` as `liu-2026-hd-mea-roadmap-implication`.
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- **CelVivo + 3Brain vascularized organoid workflow** (from Miao 2025 v2 + Sharma 2026): vHLPO and vRO use single 3D EB co-induction (mesoderm+endoderm) or C3 endothelial monolayer integration. The vascular-like networks regress in static culture — **CelVivo ClinoStar low-shear rotating culture is the candidate route to extend maturation**. Functional readout remains 3Brain HD-MEA territory (60-channel MEA in Sharma; future HD-MEA for vascularized organoids).
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- **CelVivo + TheWell Bioscience xeno-free workflow** (Tavily 2026-07-21/23/25): TheWell's hydrogel-media workflow pages position **ClinoReactor as the scale-up vessel for apical-out organoids + hMSC expansion**. Tracks in `/commitments.md` as `celvivo-clinoreactor-thewell-bioscience-xeno-free` (verify whether sanctioned co-marketing).
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- **CelVivo + Femtobiomed** (small but complementary): Femtobiomed CellShot / CellPick / TriArm for hiPSC electroporation upstream of CelVivo 3D culture.
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## Distribution and customer layer
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- **Agents (vendor-side technical contacts)** — [`/sources/agents.md`](/sources/agents.md) tracks Robin's actual distributor/agent network. Currently **1 active profile**: 董慧群 (CelVivo ClinoStar/ClinoReactor distributor technical contact; most fields 待补). Open question: see [`/open-questions.md`](/open-questions.md) `agent-dong-huiqun-celvivo` (agency company, region, contact info).
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- **Distributor map (261 dealers across 7 regions, 2026-07-24)** — [`/sources/distributors-china-2026.md`](/sources/distributors-china-2026.md). Regional distribution: 华北 74 / 华东 68 / 华南 62 / 山东 25 / 湖北 19 / 西北 6 / 西南 7. Brand keyword map (top brands by region) is preserved. **Sensitive fields (phone/微信/邮箱/终端客户清单/商机金额) are not stored here** — they live in the private Obsidian vault.
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- **Active CelVivo commercial docs** — `05-Documents/Products/Celvivo/Industrial-Customers/` (惠百生物 demo discount agreement, 2026-06-21 PO盖章版, 2026 global distributor price book) — see [`/sources/git-repo.md`](/sources/git-repo.md) Notable entities.
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## Regulatory and China-specific context
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- **China CDE cell & gene therapy classification rules (2026-07-24)** — affects CelVivo-class deals in the Chinese pharma R&D / CDMO customer base. Tracks in [`/commitments.md`](/commitments.md) `china-cde-cell-gene-therapy-rules-2026`.
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- **China Order No. 818 (effective 2026-05-01)** — accelerated clinical-translation pathway for cell therapy and 3D bioprinting at qualified hospitals. Tracks as `china-order-no-818-clinical-translation`.
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- **Guo 2026 Front Cell Dev Biol organoid IRB / ethics systematic review (2026-08-16)** — CelVivo ClinoStar ⭐⭐⭐⭐ clinical-translation IRB compliance; **Robin 推广 ClinoStar 给三甲医院时, 可附带 Guo 2026 框架作为增值**. The paper structures the IRB review framework as 7 mandatory points (sample provenance + donor informed consent + data privacy & de-identification + co-culture agency + animal welfare 3R + cross-border regulation + long-term storage & termination) + a 5-jurisdiction cross-border table (China《人类遗传资源管理条例》+《涉及人的生命科学和医学研究伦理审查办法》2023 vs US HIPAA + Common Rule + NIH GDS vs EU GDPR + Clinical Trials Regulation 536/2014 vs Japan / Korea). 3-commit LDR cycle 2026-08-16 (`2e6f5989` → `00f824f2` → `a4fa5a32`). Wiki.js ID 1724, NocoDB Id 3298, DOI 10.3389/fcell.2026.1721946. **Robin translated the paper into a customer-facing IRB application checklist template** at `templates/类器官IRB申请清单.md` v1.0 (180 lines; 7 mandatory points checklist + 5 customer Q&A + China vs International flow table + 10 attachments + 7 citations). Tracks in `/commitments.md` as `guo-2026-organoid-irb-checklist-rollout` (Owner: me; fold IRB application checklist into CelVivo industrial-customers program + Robin customer-training core material; commit the template and add a synthesis page at `/sources/literature-guo-2026-front-cell-dev-biol-organoid-ethics-deepread.md`). Vault path: `obsidian-vault/Literature/Deep-Reads/Organoid/guo_2026_organoid_ethical_review.md` (170 lines + 3 真图).
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- **China CGT 2026-07 developments** — Merck–Bio-Techne $11.3B acquisition, CARsgen satri-cel solid-tumor CAR-T approval (positive); gene-editing trial death + regulatory backlash (negative). Tracks as `china-cgt-2026-july-developments`.
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## Cross-cutting relationship
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- **Vendor-channel evidence flows:** [`/sources/web-search.md`](/sources/web-search.md) is the primary vendor-news surface; Tavily answer text is **untrusted** (mis-attribution is common on this lane — see the consistent MO:BOT mis-attribution as ClinoReactor / 3Brain EEG-headset mis-attribution as CorePlate). Trust URLs + score + published date; treat answer text as low-confidence.
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- **Literature deep-read pipeline:** [`/sources/literature.md`](/sources/literature.md) tracks every paper Robin has read. Recent 30-day CelVivo count: 5; 3Brain: 1; adjacent vendors: 2. Most deep reads are routed into [`/themes/05-robin-research.md`](/themes/05-robin-research.md).
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- **Daily-driver AI tools touch this theme** through [`/themes/03-ai-agents.md`](/themes/03-ai-agents.md) (literature-deep-read SOP, RAGFlow KB cross-query). The MiniMax-M3 model is what reads CelVivo/3Brain PDFs during the LDR workflow.
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## What to read next
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| Question | Go to |
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| --- | --- |
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| What is ClinoReactor's pricing? | [`/sources/sales-ammunition.md`](/sources/sales-ammunition.md) |
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| What does the CelVivo brain organoid whitepaper actually say? | [`/sources/literature-celvivo-brain-whitepaper-2026.md`](/sources/literature-celvivo-brain-whitepaper-2026.md) |
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| What is Raji 2026's PD drug screening story? | [`/sources/literature-raji-2026-deepread.md`](/sources/literature-raji-2026-deepread.md) |
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| What is Miao 2025's vascularized lung/gut organoid story? | [`/sources/literature-miao-2025-cell-vascularization-v2-deepread.md`](/sources/literature-miao-2025-cell-vascularization-v2-deepread.md) |
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| What is Liu 2026's shape-conformal neural organoid e-phys story? | [`/sources/literature-liu-2026-nbme-shape-conformal-organoid-deepread.md`](/sources/literature-liu-2026-nbme-shape-conformal-organoid-deepread.md) |
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| What is Sharma 2026's vascularized retinal organoid RGC story? | [`/sources/literature-sharma-2026-cell-stem-cell-vascularized-retinal-organoid-rgc-deepread.md`](/sources/literature-sharma-2026-cell-stem-cell-vascularized-retinal-organoid-rgc-deepread.md) |
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| What is Liang 2026's liver organoid fibrosis platform story? | `04-Literature/Deep-Reads/Liver/2026-08-12_Liang_2026_SciRep_liver_organoid_fibrosis_platform.md` (vault path; deep-read synthesis not yet split out to `/sources/`) |
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| What is Quintard 2024's vascularized organoid chip story? | `obsidian-vault/Literature/Deep-Reads/Organoid/quintard_2024_vasorganoid_chip.md` (vault path; deep-read synthesis not yet split out to `/sources/`) |
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| What is Guo 2026's organoid IRB / ethics story? | `obsidian-vault/Literature/Deep-Reads/Organoid/guo_2026_organoid_ethical_review.md` (vault path; deep-read synthesis not yet split out to `/sources/`) |
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| What is the IRB application checklist for organoid research? | `templates/类器官IRB申请清单.md` v1.0 (vault path; untracked) |
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| What distributors am I actually working with? | [`/sources/agents.md`](/sources/agents.md) |
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| Which Chinese dealers carry our brand? | [`/sources/distributors-china-2026.md`](/sources/distributors-china-2026.md) |
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| What regulatory shifts affect our Chinese pharma deals? | [`/commitments.md`](/commitments.md) China CDE / Order No. 818 / Guo 2026 IRB / China CGT items |
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| What conferences is 3Brain at this season? | [`/commitments.md`](/commitments.md) `3brain-coreplate-2026-conference-positioning` |
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| What's the CelVivo → 3Brain joint workflow? | [`/themes/01-organoid-equipment.md`](/themes/01-organoid-equipment.md) (this page) Workflow chain section | |