ACROBiosystems · AIDD 抗体验证服务ACROBiosystems · AIDD Antibody Validation

CHODirect

从全抗序列到 KD From full-IgG sequence to KD

AI 一天能设计上千条序列,湿实验一轮验证要 7–10 天。CHODirect 把这一轮压到快至 4 天——真实全长 IgG、CHO 细胞表达、上清直接上机不纯化,交付的是能直接进训练管线的结构化数据。

AI designs a thousand sequences a day; the wet lab needs 7–10 days per validation round. CHODirect compresses that round to as few as 4 days — real full-length IgG, expressed in CHO, supernatant straight onto the instrument with no purification. What comes back is structured data that goes directly into your training pipeline.

BLI SENSORGRAM · N=12 · SINGLE CONCHIGH-THROUGHPUT
nm ASSOCIATION DISSOCIATION
KD
4.8 nM
ka 1/Ms
5.1e5
kd 1/s
2.4e-3
0.991
全长 IgG / VHH / 小蛋白 均可Full-length IgG / VHH / mini-protein all supported CHO 体系 与商业化生产同源CHO system same host as manufacturing CSV 原生交付 不是 PDFNative CSV not a PDF
HUMANISED VH DOMAIN · RESIDUE CLASS D E K R H S T N Q Y C A V L I M F W P G

01 问题Problem

卡住 AIDD 的从来不是模型,是验证What throttles AIDD isn't the model. It's validation.

模型迭代速度已经远超湿实验。验证环节每慢一天,模型就少拿一天的真实反馈。Model iteration has long outpaced the wet lab. Every day validation lags is a day the model goes without real feedback.

7–10 天7–10 days

验证跟不上迭代Validation can't keep up

传统 CHO 表达加纯化要 7 到 10 天。模型一天产出成百上千条序列,实验验证成了唯一的节流阀。

Conventional CHO expression plus purification takes 7 to 10 days. A model produces hundreds of sequences a day, so experimental validation becomes the only throttle in the loop.

GIGO

靶点质量决定数据质量Target quality sets data quality

低活性、错误构象的靶点蛋白,产出错误的亲和力与功能数据,直接污染训练集。

Low-activity target protein in the wrong conformation produces wrong affinity and function data — and contaminates the training set directly.

KD only

功能数据缺失No functional data

多数服务止步于快速表达和 KD。没有细胞层面的功能验证,模型学不到真正的 MoA 与成药性规律。

Most providers stop at fast expression and KD. Without cell-level functional validation, a model never learns real MoA or developability rules.

单季度(90 天)可完成的验证轮次Validation rounds per 90-day quarter

传统 CHO 表达纯化Conventional CHO + purification
11 轮11 rounds
CHODirect
22 轮22 rounds

按传统流程 8 天/轮的中值估算。对 AIDD 而言,这意味着回流进模型的实验数据量翻倍——不是快一点,是多一倍的训练信号。

Estimated at a midpoint of 8 days per conventional round. For AIDD this means twice the experimental data flowing back into the model — not marginally faster, but double the training signal.

02 流程Flow

快至四天,逐日拆开看As fast as four days, taken day by day

自客户提交序列当天起算。省掉的是抗体纯化环节——传统流程里最耗时的一段。Counted from the day you submit your sequence. What we remove is antibody purification — the longest stretch of the conventional workflow.

DAY 0

序列提交与分析Sequence submission

  • 在线输入全抗体序列
  • AI 自动序列分析
  • AI 辅助密码子优化
  • Full-IgG sequence submitted online
  • Automated AI sequence analysis
  • AI-assisted codon optimisation
DAY 1

基因合成与构建Synthesis & cloning

  • 快速基因合成
  • 自动化无缝衔接,不排队
  • Rapid gene synthesis
  • Automated hand-off, no queue
DAY 2

CHO 转染表达CHO transfection

  • 改造 CHO 细胞株
  • 转染 24 小时达高表达
  • IgG 正确折叠与翻译后修饰
  • Engineered CHO cell line
  • High expression within 24 h
  • Correct folding and PTMs
DAY 3

上清收获与检测Harvest & measurement

  • 上清直接检测,无需纯化
  • BLI 高通量亲和力测定
  • 多点动力学参数分析
  • Supernatant read directly, no purification
  • High-throughput BLI affinity
  • Multi-point kinetic analysis
DAY 4

数据自动交付Automated delivery

  • 结构化数据在线下载
  • 全流程可追溯
  • 无邮件往返
  • Structured data downloaded online
  • Fully traceable workflow
  • No email round-trips
DAY 0 / 共 5 个节点/ 5 stages
关键差异:上清直接上机,跳过纯化;CHO 的折叠与糖基化修饰与商业化 CHO 生产体系同源,早期筛出来的数据可以直接指导后续开发,不必担心换体系后构象漂移。 The key difference: supernatant goes straight onto the instrument, skipping purification; and CHO folding and glycosylation match the commercial CHO manufacturing system, so early screening data carries forward into development without the conformational shift you inherit when the host changes.

03 闭环The loop

一轮结束,就是下一轮的输入One round ends as the next round's input

AIDD 不是一次性的筛选,是一个不断收紧的循环。每转完一轮,就有新一轮真实数据回流给模型;循环完成得越快,模型积累的真实数据就越多。AIDD isn't a one-shot screen; it's a loop that keeps tightening. Each completed turn sends a new round of real data back to the model — the faster each turn completes, the more real data the model accumulates.

01 · DESIGN

模型设计序列The model designs

生成模型一天产出成百上千条候选全抗序列,等待被真实世界打分。

A generative model produces hundreds of candidate full-IgG sequences a day, waiting to be scored by the real world.

02 · EXPRESS

CHO 表达真实分子CHO expresses the real molecule

合成、转染、分泌真实分子——从全长 IgG 到 VHH / 小蛋白,检测的都是最终形式本身,不是替身。

Synthesis, transfection, secretion of the real molecule — from full-length IgG to VHH or mini-protein, what is measured is the final format itself, not a proxy.

04 · LEARN

数据回流训练Data flows back

结构化记录直接进管线,成功与失败的样本都保留——负样本同样是训练信号。

Structured records go straight into the pipeline; hits and non-binders are both kept — a negative is training signal too.

03 · MEASURE

BLI 测出结合动力学BLI measures the kinetics

上清直接上机,得到 KD、ka、kd 与拟合优度,附带原始曲线。

Supernatant goes straight onto the instrument, yielding KD, ka, kd and goodness of fit, with the raw trace attached.

快至四天转一圈。季度内多转 11 圈,模型多拿一倍的真实反馈——这是速度对 AIDD 唯一有意义的定义。

As fast as four days per turn. Eleven extra turns a quarter, and the model gets twice the real feedback — which is the only definition of speed that matters to AIDD.

04 交付物Deliverable

你拿到的不是一份 PDFWhat you get is not a PDF

每一条设计对应一条结构化记录,含原始曲线、动力学参数与拟合优度。交付不止 KD——从序列到结合动力学全过程的数据(含原始数据)均可提供。字段字典随首次交付一并提供。Every design maps to one structured record carrying the raw trace, the kinetic parameters and the goodness of fit. Delivery goes beyond KD — data across the whole sequence-to-kinetics workflow, including raw data, is available. The field dictionary ships with the first delivery.

design_id,assay,kd_nM,ka_1/Ms,kd_1/s,fit_r2,rmax_nm,raw_trace_csvAb-001,BLI,13.2,2.4e5,3.2e-3,0.994,0.51,Ab-001_raw.csvAb-002,BLI, 4.8,5.1e5,2.4e-3,0.991,0.42,Ab-002_raw.csvAb-003,BLI,  — ,  — ,  — ,  — ,0.03,Ab-003_raw.csvAb-004,BLI,27.6,1.8e5,4.9e-3,0.988,0.47,Ab-004_raw.csvAb-005,BLI, 0.9,7.6e5,6.8e-4,0.996,0.55,Ab-005_raw.csv

字段字典Field dictionary

给的是测量事实与拟合指标,不是替你下的合格判定——阈值由你的管线来定。经验分析可作为额外数据交付:可按既定规则与算法赋值的高通量数据直接给出分析值,需人工判断的部分单独标注、置于标准数据包之外。

What ships are measurement facts and fit metrics, not a pass/fail verdict made on your behalf — the thresholds belong to your pipeline. Experience-based interpretation is available as an additional deliverable: rule- and algorithm-based analysis values where high-throughput data allows, and manually assessed items flagged separately, outside the standard data package.

字段含义
design_id与你提交时的命名一一对应
assay检测方法
kd_nM平衡解离常数
ka_1/Ms结合速率常数
kd_1/s解离速率常数
fit_r2拟合优度
rmax_nm响应幅度,信号强弱的直接证据
raw_trace_csv该样本的原始曲线文件(时间-响应两列)
FieldMeaning
design_idMaps one-to-one to your own naming
assayMeasurement method
kd_nMEquilibrium dissociation constant
ka_1/MsAssociation rate constant
kd_1/sDissociation rate constant
fit_r2Goodness of fit
rmax_nmResponse amplitude — direct evidence of signal strength
raw_trace_csvRaw curve file for that sample (time / response columns)
  • CSV 与 JSON 双格式同时交付,字段字典随首次交付提供
  • 原始曲线随记录一起给,你可以自行复核拟合是否合理
  • 无结合的样本照样进包(如 CSV 里的 Ab-003),保留行、带响应幅度,不做删除处理
  • CSV and JSON are delivered together, with the field dictionary included in the first delivery
  • The raw trace ships with the record, so you can re-check the fit yourself
  • Non-binders stay in the package (Ab-003 in the CSV) — the row is kept with its response amplitude, never silently dropped

05 不止 KDBeyond KD

从蛋白到细胞,再到类器官From protein to cell to organoid

四天这一轮解决的是排序:谁值得往下做。进入 Leads 阶段后,纯化蛋白进入完整的功能与成药性验证——这是把「能不能结合」变成「能不能起效」的地方。

The four-day round solves ranking: which designs are worth taking further. At the Leads stage, purified protein enters full functional and developability validation — this is where does it bind becomes does it work.

L1

蛋白层Protein level

理化 · 亲和力 · 初步成药性Biophysics · Affinity · Preliminary developability

  • SPR / BLI 多点亲和力与动力学
  • nanoDSF:Tm / Tonset
  • DLS / SLS:粒径、PDI、聚集倾向
  • SEC-HPLC / SEC-MALS 聚集体分析
  • Self-interaction:kD / B22、AC-SINS
  • ELISA / TR-FRET blocking
  • TR-FRET FcγR 结合:Fc 效应相关筛选
  • TR-FRET FcRn 结合:半衰期相关筛选
  • 交叉反应与特异性
  • Multi-point SPR / BLI affinity and kinetics
  • nanoDSF: Tm / Tonset
  • DLS / SLS: size, PDI, aggregation propensity
  • SEC-HPLC / SEC-MALS aggregate analysis
  • Self-interaction: kD / B22, AC-SINS
  • ELISA / TR-FRET blocking
  • TR-FRET FcγR binding: Fc effector screening
  • TR-FRET FcRn binding: half-life screening
  • Cross-reactivity and specificity
L2

细胞层Cell level

MoA 验证 · 效应功能MoA validation · Effector function

  • 过表达株 Flow binding
  • KO / 靶点阴性株特异性验证
  • 增殖、凋亡、内吞
  • ADCC / ADCP、Cell killing
  • 免疫检查点 T 细胞激活
  • 通路抑制 / 激动活性与 Crosslinking
  • Cytokine profiling
  • 300+ 报告基因功能细胞株
  • Flow binding on overexpressing lines
  • Specificity on KO / target-negative lines
  • Proliferation, apoptosis, internalisation
  • ADCC / ADCP and cell killing
  • Checkpoint T-cell activation
  • Pathway inhibition / agonist activity and crosslinking
  • Cytokine profiling
  • 300+ reporter-gene functional lines
L3

类器官 / 高阶模型层Organoid / higher-order models

hiPSC 来源 · 3D 高阶模型hiPSC-derived · 3D models

  • 心脏 / 脑 / 皮肤 / 肾脏等 3D 模型
  • 3D 药效与细胞活性
  • Dose-response · EC50 / IC50
  • MEA 电生理 · 钙成像
  • 毒性与 Off-target-related response
  • 形态学与标志物读数
  • 人源遗传背景 · 来源可追溯
  • 验证药物是否引起真实的组织功能变化
  • Cardiac / brain / skin / kidney 3D models
  • 3D efficacy and cell viability
  • Dose-response · EC50 / IC50
  • MEA electrophysiology · calcium imaging
  • Toxicity and off-target-related response
  • Morphology and biomarker readouts
  • Human genetic background · traceable provenance
  • Tests whether the drug causes real changes in tissue function

06 数据从哪来Where the data comes from

验证工具本身,决定数据的上限The validation tools set the ceiling on the data

测得准的前提是靶点对。这些资源不是外采的,是同一家做出来的——所以数据前后一致、可追溯。Measuring accurately starts with the right target. These resources aren't bought in — they're built by the same company, which is why the data stays consistent and traceable.

0+

高质量重组靶点蛋白High-quality recombinant targets

逐批活性验证;HEK293 表达体系,与人体一致的糖基化与折叠;多标签、多物种、多形式覆盖。全球 Top 药企与 Biotech 广泛使用。

Lot-by-lot activity validation; HEK293 expression for human-like glycosylation and native folding; multi-tag, multi-species, multi-format coverage. Used widely by leading global pharma and biotech.

0+

难成药膜蛋白靶点Hard-to-drug membrane targets

GPCR、离子通道、转运体、GPI 锚定与黏附分子。膜蛋白占药物靶点 40% 以上,却是公开数据最稀缺的一块。

GPCRs, ion channels, transporters, GPI-anchored and adhesion molecules. Membrane proteins are over 40% of drug targets — and the scarcest public data of all.

数百株Hundreds

工程细胞株Engineered cell lines

过表达株、KO 株与 300+ 报告基因功能株。同一株细胞可从早期筛选一路用到 CMC 质量放行。

Overexpressing lines, KO lines and 300+ reporter-gene functional lines. One line carries from early screening all the way through to CMC release.

07 边界Boundaries

序列交给我们之后After you hand over the sequence

序列只用于本次委托Used only for this engagement

不进入任何内部数据库,不用于我们自己的模型训练。

Sequences never enter any internal database and are never used to train our own models.

数据所有权归你You own the data

序列及由其产生的全部实验数据,所有权与知识产权归客户。

The sequence and all experimental data derived from it — ownership and IP remain with the customer.

细胞株全球合规授权Globally licensable cell lines

覆盖中美欧主要市场,IND / BLA 申报无第三方 IP 隐患。

Covering the US, EU and China; no third-party IP exposure at IND / BLA filing.

上市公司交付Delivered by a listed company

百普赛斯集团(301080.SZ),13,000+ 客户。

ACROBiosystems Group (301080.SZ), 13,000+ customers.

08 开始Start

先拿一份真实数据包看看Take a real data package first

不用先谈合同。我们可以先发一份完整的样例数据包,或者用你手上已知 KD 的内部标准品做一轮小规模试运行——测出来的值和你手里的真值一对,准确性、报告质量、交付格式一次见分晓

No contract needed first. We can send a complete sample data package, or run a small pilot on an in-house standard whose KD you already know — compare our number against your truth and accuracy, report quality and delivery format all settle in a single round.

STEP 01

索取样例数据包Request the sample package

CSV 数据包 + 字段字典 + 一条含原始曲线的完整记录,附一行命令转 JSON。看完再决定要不要谈。

CSV package + field dictionary + one complete record with its raw trace, plus the one-line JSON conversion. Decide after you've read it.

STEP 02

签署保密协议Sign the NDA

序列提交前完成 NDA,明确使用边界与数据所有权。

Executed before any sequence is submitted, defining use boundaries and data ownership.

STEP 03

小规模试运行Run a small pilot

建议夹带你已知 KD 的标准品做盲测,用你自己的标准验收我们。

We suggest spiking in a standard whose KD you know, blinded — accept us on your own criteria.

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