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高通量筛选 - 版本历史
2026-04-09T21:49:14Z
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2026年2月3日 (二) 23:28 77921020
2026-02-03T23:28:22Z
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<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">←上一版本</td>
<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">2026年2月3日 (二) 23:28的版本</td>
</tr><tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l78" >第78行：</td>
<td colspan="2" class="diff-lineno">第78行：</td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <li style="margin-bottom: 8px;"><strong>1. 实验开发 (Assay Development)：</strong> 将生物学反应（如酶与底物结合、受体激活）转化为可检测的光学信号（如荧光、发光）。关键是使实验适应微孔板格式并具有高稳定性。</li></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <li style="margin-bottom: 8px;"><strong>1. 实验开发 (Assay Development)：</strong> 将生物学反应（如酶与底物结合、受体激活）转化为可检测的光学信号（如荧光、发光）。关键是使实验适应微孔板格式并具有高稳定性。</li></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <li style="margin-bottom: 8px;"><strong>2. 初级筛选 (Primary Screen)：</strong> 对数万至数百万个化合物进行单浓度（Single point）测试。通常设定一个阈值（如抑制率 > 50%）来挑选“活性”化合物。</li></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <li style="margin-bottom: 8px;"><strong>2. 初级筛选 (Primary Screen)：</strong> 对数万至数百万个化合物进行单浓度（Single point）测试。通常设定一个阈值（如抑制率 > 50%）来挑选“活性”化合物。</li></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> <li style="margin-bottom: 8px;"><strong>3. 命中确认 (Hit Confirmation)：</strong> 对初筛阳性孔进行复孔测试，排除<strong>假阳性</strong>（False Positives），并进行剂量-反应曲线（Dose-response）分析以测定 <del class="diffchange diffchange-inline">$\text{</del>IC<del class="diffchange diffchange-inline">}_{</del>50<del class="diffchange diffchange-inline">}$ </del>或 <del class="diffchange diffchange-inline">$\text{</del>EC<del class="diffchange diffchange-inline">}_{</del>50<del class="diffchange diffchange-inline">}$</del>。</li></div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> <li style="margin-bottom: 8px;"><strong>3. 命中确认 (Hit Confirmation)：</strong> 对初筛阳性孔进行复孔测试，排除<strong>假阳性</strong>（False Positives），并进行剂量-反应曲线（Dose-response）分析以测定 IC<ins class="diffchange diffchange-inline"><sub></ins>50<ins class="diffchange diffchange-inline"></sub> </ins>或 EC<ins class="diffchange diffchange-inline"><sub></ins>50<ins class="diffchange diffchange-inline"></sub></ins>。</li></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <li style="margin-bottom: 0;"><strong>4. 反筛选 (Counter Screen)：</strong> 排除非特异性结合或具有细胞毒性的化合物（Pan-assay interference compounds, <strong>PAINS</strong>）。</li></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <li style="margin-bottom: 0;"><strong>4. 反筛选 (Counter Screen)：</strong> 排除非特异性结合或具有细胞毒性的化合物（Pan-assay interference compounds, <strong>PAINS</strong>）。</li></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </ul></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </ul></div></td></tr>
<tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l123" >第123行：</td>
<td colspan="2" class="diff-lineno">第123行：</td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <p style="margin: 15px 0; text-align: justify;"></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <p style="margin: 15px 0; text-align: justify;"></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> 在 HTS 中，判断一个实验是否可靠，最权威的统计学参数是 <strong>[[Z因子]] (Z-Factor)</strong>。</div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> 在 HTS 中，判断一个实验是否可靠，最权威的统计学参数是 <strong>[[Z因子]] (Z-Factor)</strong>。</div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><del style="font-weight: bold; text-decoration: none;"> <br></del></div></td><td colspan="2"> </td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><del style="font-weight: bold; text-decoration: none;"> $$ Z = 1 - \frac{3(\sigma_p + \sigma_n)}{|\mu_p - \mu_n|} $$</del></div></td><td colspan="2"> </td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><del style="font-weight: bold; text-decoration: none;"> <br></del></div></td><td colspan="2"> </td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><del style="font-weight: bold; text-decoration: none;"> 其中 $\sigma$ 是标准差，$\mu$ 是平均值，$p$ 和 $n$ 分别代表阳性对照和阴性对照。</del></div></td><td colspan="2"> </td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </p></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </p></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;"></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;"> <div style="background-color: #f8fafc; padding: 20px; border-radius: 8px; border: 1px solid #e2e8f0; text-align: center; margin: 20px auto; max-width: 80%;"></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;"> <div style="font-family: 'Times New Roman', serif; font-size: 1.3em; color: #1e293b;"></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;"> Z = 1 - <span style="display: inline-block; vertical-align: middle; text-align: center;"></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;"> <span style="display: block; border-bottom: 1.5px solid #1e293b; padding-bottom: 2px;">3(&sigma;<sub>p</sub> + &sigma;<sub>n</sub>)</span></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;"> <span style="display: block; padding-top: 2px;">|&mu;<sub>p</sub> - &mu;<sub>n</sub>|</span></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;"> </span></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;"> </div></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;"> <div style="margin-top: 15px; font-size: 0.9em; color: #64748b;"></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;"> 其中 <strong>&sigma;</strong> 是标准差，<strong>&mu;</strong> 是平均值<br></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;"> <strong>p</strong> 代表阳性对照 (Positive)，<strong>n</strong> 代表阴性对照 (Negative)</ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;"> </div></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;"> </div></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;"> </ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;"> </ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;"></ins></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <ul style="padding-left: 25px; color: #334155; margin-top: 15px;"></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <ul style="padding-left: 25px; color: #334155; margin-top: 15px;"></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> <li style="margin-bottom: 8px;"><strong>1.0 > Z ≥ 0.5：</strong> <del class="diffchange diffchange-inline">优秀的筛选实验（Excellent）。</del></li></div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> <li style="margin-bottom: 8px;"><strong>1.0 > Z ≥ 0.5：</strong> <ins class="diffchange diffchange-inline">优秀的筛选实验（Excellent）。信号窗口大，误差小。</ins></li></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> <li style="margin-bottom: 8px;"><strong>0.5 > Z > 0：</strong> <del class="diffchange diffchange-inline">勉强可用（Marginal），需优化。</del></li></div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> <li style="margin-bottom: 8px;"><strong>0.5 > Z > 0：</strong> <ins class="diffchange diffchange-inline">勉强可用（Marginal），可能需要优化。</ins></li></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> <li style="margin-bottom: 0;"><strong>Z < 0：</strong> <del class="diffchange diffchange-inline">实验失败，无法区分信号与噪音。</del></li></div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> <li style="margin-bottom: 0;"><strong>Z < 0：</strong> <ins class="diffchange diffchange-inline">实验失败。信号与背景重叠，无法区分。</ins></li></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </ul></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </ul></div></td></tr>
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77921020
https://www.yiliao.com/index.php?title=%E9%AB%98%E9%80%9A%E9%87%8F%E7%AD%9B%E9%80%89&diff=316322&oldid=prev
77921020：建立内容为“<div style="padding: 0 4%; line-height: 1.8; color: #1e293b; font-family: 'Helvetica Neue', Helvetica, 'PingFang SC', Arial, sans-serif; background-color: #ffffff…”的新页面
2026-02-03T23:26:09Z
<p>建立内容为“<div style="padding: 0 4%; line-height: 1.8; color: #1e293b; font-family: 'Helvetica Neue', Helvetica, 'PingFang SC', Arial, sans-serif; background-color: #ffffff…”的新页面</p>
<p><b>新页面</b></p><div><div style="padding: 0 4%; line-height: 1.8; color: #1e293b; font-family: 'Helvetica Neue', Helvetica, 'PingFang SC', Arial, sans-serif; background-color: #ffffff; max-width: 1200px; margin: auto;"><br />
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<strong>高通量筛选</strong>（High-Throughput Screening，HTS）是现代药物发现工业化流程中的核心技术。它利用精密的自动化机器人系统、高灵敏度的微板检测仪器和强大的数据处理软件，在微孔板（如 384 孔或 1536 孔板）上对数以万计甚至百万计的 <strong>[[化合物库]]</strong> 进行快速、并行的生物活性测试。HTS 的核心目标是从海量样本中筛选出能够特异性调节生物靶点（如激酶、GPCR）活性的 <strong>[[苗头化合物]] (Hits)</strong>，为后续的 <strong>[[先导化合物]]</strong> 优化奠定基础。近年来，随着 <strong>[[DNA编码化合物库]] (DEL)</strong> 和 <strong>[[CRISPR筛选]]</strong> 的出现，HTS 的通量和维度得到了指数级的提升。<br />
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<div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">高通量筛选</div><br />
<div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">High-Throughput Screening (点击展开)</div><br />
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<div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">药物发现的工业引擎</div><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f8fafc; color: #475569; border-bottom: 1px solid #e2e8f0; width: 40%;">英文缩写</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">HTS</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f8fafc; color: #475569; border-bottom: 1px solid #e2e8f0;">通量定义</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">&gt;10,000 样本/天</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f8fafc; color: #475569; border-bottom: 1px solid #e2e8f0;">关键耗材</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">384/1536 孔板</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f8fafc; color: #475569; border-bottom: 1px solid #e2e8f0;">筛选对象</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #16a34a;">小分子, siRNA, CRISPR</td><br />
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<th colspan="2" style="padding: 8px 12px; background-color: #e0f2fe; color: #1e40af; text-align: left; font-size: 0.9em; border-top: 1px solid #bae6fd;">质量控制</th><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f8fafc; color: #475569; border-bottom: 1px solid #e2e8f0;">核心指标</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #e11d48;">[[Z因子]] (Z-Factor)</td><br />
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<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">0.5 < Z < 1.0</td><br />
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<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">S/N > 10</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f8fafc; color: #475569;">进阶技术</th><br />
<td style="padding: 6px 12px; color: #1e40af;">[[高内涵筛选]] (HCS)</td><br />
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HTS 是一个跨学科的系统工程，其标准流程通常包括四个阶段：<br />
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<li style="margin-bottom: 8px;"><strong>1. 实验开发 (Assay Development)：</strong> 将生物学反应（如酶与底物结合、受体激活）转化为可检测的光学信号（如荧光、发光）。关键是使实验适应微孔板格式并具有高稳定性。</li><br />
<li style="margin-bottom: 8px;"><strong>2. 初级筛选 (Primary Screen)：</strong> 对数万至数百万个化合物进行单浓度（Single point）测试。通常设定一个阈值（如抑制率 > 50%）来挑选“活性”化合物。</li><br />
<li style="margin-bottom: 8px;"><strong>3. 命中确认 (Hit Confirmation)：</strong> 对初筛阳性孔进行复孔测试，排除<strong>假阳性</strong>（False Positives），并进行剂量-反应曲线（Dose-response）分析以测定 $\text{IC}_{50}$ 或 $\text{EC}_{50}$。</li><br />
<li style="margin-bottom: 0;"><strong>4. 反筛选 (Counter Screen)：</strong> 排除非特异性结合或具有细胞毒性的化合物（Pan-assay interference compounds, <strong>PAINS</strong>）。</li><br />
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为了在微升体系中获得高信噪比，HTS 依赖于先进的光学检测技术。<br />
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<th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 20%;">技术类别</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af; width: 25%;">代表方法</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569; width: 55%;">原理与优势</th><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">荧光技术</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">[[FRET]], TR-FRET, FP</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>荧光共振能量转移</strong> (FRET) 可检测分子间距离变化（如蛋白-蛋白相互作用）。TR-FRET 利用长寿命荧光（如铕）消除背景干扰。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">发光技术</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">Luciferase, ATP Lite</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">利用萤火虫荧光素酶。背景极低，灵敏度极高，常用于检测细胞活力或基因报告系统。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">高内涵</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">[[高内涵筛选]] (HCS)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">结合<strong>自动显微成像</strong>与图像分析。不仅看“死活”，还能看蛋白定位、细胞形态、神经突触生长等复杂表型。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">非标记</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">SPR, 质谱 (SAMDI)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">无需荧光标记，直接检测分子质量或折射率变化，避免标记对活性的影响。</td><br />
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在 HTS 中，判断一个实验是否可靠，最权威的统计学参数是 <strong>[[Z因子]] (Z-Factor)</strong>。<br />
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$$ Z = 1 - \frac{3(\sigma_p + \sigma_n)}{|\mu_p - \mu_n|} $$<br />
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其中 $\sigma$ 是标准差，$\mu$ 是平均值，$p$ 和 $n$ 分别代表阳性对照和阴性对照。<br />
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<li style="margin-bottom: 8px;"><strong>1.0 > Z ≥ 0.5：</strong> 优秀的筛选实验（Excellent）。</li><br />
<li style="margin-bottom: 8px;"><strong>0.5 > Z > 0：</strong> 勉强可用（Marginal），需优化。</li><br />
<li style="margin-bottom: 0;"><strong>Z < 0：</strong> 实验失败，无法区分信号与噪音。</li><br />
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<span style="color: #0f172a; font-weight: bold; font-size: 1.05em; display: inline-block; margin-bottom: 15px;">学术参考文献 [Academic Review]</span><br />
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[1] <strong>Zhang JH, Chung TD, Oldenburg KR. (1999).</strong> <em>A Simple Statistical Parameter for Use in Evaluation and Validation of High Throughput Screening Assays.</em> <strong>[[Journal of Biomolecular Screening]]</strong>. <br><br />
<span style="color: #475569;">[点评]：经典文献。提出了 Z-Factor 概念，成为衡量 HTS 数据质量的行业金标准。</span><br />
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[2] <strong>Macarron R, et al. (2011).</strong> <em>Impact of high-throughput screening in biomedical research.</em> <strong>[[Nature Reviews Drug Discovery]]</strong>. <br><br />
<span style="color: #475569;">[点评]：全面回顾了 HTS 技术在过去几十年中对新药发现的贡献，讨论了从靶点筛选到表型筛选的转变。</span><br />
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[3] <strong>Abraham BK, et al. (2004).</strong> <em>High content screening applied to large-scale cell biology.</em> <strong>[[Trends in Biotechnology]]</strong>. <br><br />
<span style="color: #475569;">[点评]：讨论了 HTS 向 HCS（高内涵）的进化，强调了图像数据在理解复杂细胞生物学中的价值。</span><br />
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药物筛选技术网络 · 知识图谱<br />
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<td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle;">上级学科</td><br />
<td style="padding: 10px 15px; color: #334155;">[[药物发现]] • [[生物技术]]</td><br />
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<td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle;">核心资源</td><br />
<td style="padding: 10px 15px; color: #334155;">[[化合物库]] • [[DEL]] • [[CRISPR文库]] • 细胞株</td><br />
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<td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle;">衍生技术</td><br />
<td style="padding: 10px 15px; color: #334155;">[[虚拟筛选]] (CADD) • [[高内涵筛选]] (HCS) • [[片段筛选]] (FBDD)</td><br />
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