中国科学院深圳先进技术研究院,生物医学与健康工程研究所, 医学成像科学与技术系统全国重点实验室,广东 深圳 518055
[ "谭骁天(1995—),男,博士,副研究员,硕士生导师,中国科学院深圳先进技术研究院仿生触觉与智能传感研究中心主任助理。研究方向为光微流生物分子传感技术、激光发射生物传感、面向生物分子探测的蛋白设计等。E-mail:xt.tan@siat.ac.cn" ]
[ "李睿涵(1997—),男,助理研究员。研究方向为面向生物传感的蛋白探针设计。E-mail:rh.li@siat.ac.cn" ]
[ "杨慧(1983—),女,博士,研究员,博士生导师,中国科学院深圳先进技术研究院仿生触觉与智能传感研究中心主任。研究方向为生物医学微纳米操控与超灵敏传感技术研究。E-mail:hui.yang@siat.ac.cn" ]
收稿:2024-12-02,
修回:2025-01-03,
纸质出版:2026-02-28
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谭骁天, 李睿涵, 杨慧. 生物分子传感中的抗体探针:由碳基计算走向硅基计算[J]. 合成生物学, 2026, 7(1): 93-101
TAN Xiaotian, LI Ruihan, YANG Hui. Antibody probes in biomolecular sensing: from carbon-based computing to silicon-based computing[J]. Synthetic Biology Journal, 2026, 7(1): 93-101
谭骁天, 李睿涵, 杨慧. 生物分子传感中的抗体探针:由碳基计算走向硅基计算[J]. 合成生物学, 2026, 7(1): 93-101 DOI: 10.12211/2096-8280.2024-085.
TAN Xiaotian, LI Ruihan, YANG Hui. Antibody probes in biomolecular sensing: from carbon-based computing to silicon-based computing[J]. Synthetic Biology Journal, 2026, 7(1): 93-101 DOI: 10.12211/2096-8280.2024-085.
蛋白质等生物大分子在疾病诊断与治疗、基础科学研究中占据核心地位,而抗体探针作为免疫分析的关键工具,其重要性日益凸显。近年来,抗体探针的设计、预测与生成正经历从传统的基于动物免疫的“碳基计算”向人工智能驱动的“硅基计算”的革命性转型。传统的抗体生成技术依赖动物免疫,不仅效率低下,且难以精准控制。人工智能的引入为抗体设计带来了突破,实现了高特异性、高亲和力抗体探针的快速生成及抗原表位的精准预测。这一转变不仅能提高抗体类蛋白探针的性能,也缩短了研发周期。本文介绍了抗体生成技术的演进历程,分析了人工智能在抗体设计中的应用优势与挑战,并展望了抗体类蛋白探针与新一代生物传感器的协同发展前景。随着蛋白结合蛋白(PBP)预测技术的成熟,蛋白质从头设计研究人员有望通过“硅基计算”与“硅基性能表征”,快速生成满足特定需求的探针分子,同时实现抗原表位及分子功能的精确预测。结合新一代高灵敏生物传感技术,人工智能辅助设计的非天然蛋白探针将显著提升免疫分析灵敏度,拓展可分析的分子信息类型,推动免疫分析向多维化方向发展。这一创新不仅为合成生物学研究开辟了新的研究路径,也将为精准医学诊断方法的开发提供有力支撑。
The precise recognition
detection
and analysis of protein biomarkers are essential for disease diagnosis and life sciences research. Antibody probes
known for their high specificity and stability
are crucial to biomolecular sensing assays. Traditionally
antibody development has relied on “carbon-based” approaches using animal immune systems. However
we are currently undergoing a transformative shift toward “silicon-based” methods driven by artificial intelligence (AI). Conv
entional techniques
such as animal-based antibody production and phage display-based directed evolution
have long been challenged by low efficiency and limited control over epitope specificity and binding affinity. Recent AI advances
including
de
novo
protein design and deep learning-driven protein binding protein (PBP) generation
are revolutionizing antibody development. These innovations enable the rapid creation of protein-based biosensing probes (
e.g.
antibodies and nanobodies) with enhanced specificity and affinity
along with accurate predictions of epitopes and structural features. By overcoming limitations with traditional methods
AI-driven technologies offer unprecedented control over the design and performance of antibody probes. Furthermore
“silicon-based evaluation” plays a key role in PBP generation
allowing for quantitative assessment of binding affinity
stability
and robustness. AI-designed biosensing probes offer potentials for capturing a broader spectrum of biomolecular information
which may be able to detect variations in sequence and conformation
post-translational modifications
abnormal polymerization
and shifts in biological activity. In certain diseases
the abnormal dissociation of multimeric proteins can reveal previously concealed antigenic epitopes
creating disease-specific targets
which can be better addressed with AI-designed probes for more accurate and nuanced insights. Moreover
modern high-performance biomolecular sensing technologies
such as bead-based chemiluminescent immunoassays (CLIA)
digital immunoassay
microfluidic immunoassay
and single molecule binding kinetics assays
require highly diverse antibody specificity and affinity
and AI-based protein design tools can meet these divergent needs
enabling the integration of AI-engineered biosensing probes with next-generation sensors. This integration not only enhances detection sensitivity
but also expands the scope of molecular information that can be ana
lyzed. Such a paradigm shift represents a new era in biomolecular sensing
and offers exciting prospects for precision medicine and synthetic biology.
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