Label Free Pharmaceutical Anticounterfeiting Technology

描述（由申请人提供）：假冒消费品、文件和其他贵重物品一直是人类长期存在的普遍问题。也许最昂贵和最应受道德谴责的制假形式是制造假冒药品。从富裕国家为提高生活质量而开出的昂贵药物，到非洲的整个供应链，据估计，非洲80%的药品都是假冒的。然而，在药丸水平上直接保护药物制剂的防伪方法在采用满足FDA的方法方面提出了一套非常严格的要求。这里提出了一种非常便宜的方法，不可能逆向工程或复制，可以以与制造速度相称的速度直接在药丸级别标记药物，并且无需FDA批准，因为该技术是“无标签”的，这意味着没有化学物质添加到药物中。该技术基于一系列微机械压印邮票，具有微米到纳米的分层特征，将编码信息直接压印在薄膜涂层药物制剂上。压印邮票是用电子束在硅片上刻写一系列尺寸从50微米到50纳米不等的特征来制备的。在使用深度反应离子蚀刻（DRIE）将这些特征蚀刻到~100- 5000nm后，通过在硅母片上电镀（即电铸）镍钴合金制成负模。然后，这个负金属印记被用来压印包裹药丸的聚合物薄膜，以传递小至20纳米的特征。压花特征将包括尺寸为100微米、5微米、500纳米和50纳米的特征层次结构。消费者可以用放大镜看到100纳米的特征，药店用光学显微镜看到5纳米的特征，批发分销水平用扫描电镜看到500纳米的特征，制造过程中用扫描电镜或原子力显微镜看到50纳米的特征。由于用于制造最小特征的技术操作略低于其最佳分辨率范围，因此无法复制印章，从而产生许多不可能复制的独特和随机缺陷。

DESCRIPTION (provided by applicant): The counterfeiting of consumer goods, documents and other valuable objects has always been a perpetual and widespread problem for humankind. Perhaps the most costly and morally reprehensible form of counterfeiting is the manufacture of counterfeit pharmaceutical products. Imitations range from expensive drugs prescribed in affluent countries to increase the quality of life to the entire supply chain in Africa where it is estimated that >80% of all pharmaceutical products are counterfeit. However, an anticounterfeiting method to protect pharmaceutical preparations directly at the pill level presents a singularly stringent set of requirements in terms of employing a method that would satisfy the FDA. A method is proposed here which is very inexpensive, impossible to reverse engineer or replicate, can label the pharmaceutical directly at the pill level at a speed commensurate with manufacturing rates and with no FDA approval as the technique is "label free" meaning that no chemical was added to the pharmaceutical. The technology is based on a series of micromachined embossing stamps with hierarchical micron to nanometer features that emboss encoded information directly onto the thin film coating pharmaceutical preparations. The embossing stamps are prepared by writing a series of features of decreasing size, from 50 ¿m to around 50 nm, onto an Si wafer with an electron beam. After etching these features to ~100-5000 nm using Deep Reactive Ion Etching (DRIE), a negative mold is made by electroplating (i.e. electroforming) a Ni-Co alloy onto the silicon master. This negative metal stamp is then used to emboss the polymer film encapsulating the pill transferring features as small as 20nm. The embossed features will comprise a hierarchy of features with sizes of 100¿m, 5¿m, 500nm and 50nm. The 100¿m features can be visualized by the consumer with a magnifying glass, the 5¿m features at a pharmacy with an optical microscope, the 500nm features at the wholesale distribution level with an SEM, and the 50nm scale during manufacture with an SEM or AFM. The stamp cannot be replicated, as the technology used to fabricate the smallest features is operated slightly below its optimum resolution range, thereby generating many impossible to duplicate unique and random defects. The "LFAT" technology developed in this proposal represents a system in which pharmaceutical products can be labeled and detected by the manufacturer, distributor or consumer. The identifying features are impossible to replicate and easy to apply, without any need for FDA approval. This technology can be rapidly deployed to prevent the illnesses and suffering caused by consumption of counterfeit products.