Label Free Pharmaceutical Anticounterfeiting Technology

消费品、文件和其他有价值物品的伪造一直是人类的一个永久和普遍的问题。也许最昂贵和道德上最应受到谴责的假冒形式是制造假冒药品。仿制品的范围从富裕国家为提高生活质量而开出的昂贵药品到非洲的整个供应链，据估计，非洲80%以上的药品都是假冒的。然而，直接在药丸水平上保护药物制剂的防伪方法在采用将满足FDA的方法方面提出了一组非常严格的要求。这里提出了一种方法，该方法非常便宜，不可能进行逆向工程或复制，可以以与制造速率相称的速度直接在药丸水平上标记药物，并且没有FDA批准，因为该技术是“无标签”的，这意味着没有化学物质被添加到药物中。该技术是基于一系列微机械压印邮票与层次微米到纳米的功能，将编码信息直接到薄膜涂层药物制剂。通过用电子束在Si晶片上写入一系列尺寸从50 μ m减小到约50 nm的特征来制备压印印模。在使用深反应离子蚀刻（DRIE）将这些特征蚀刻至约100-5000 nm之后，通过将Ni-Co合金电镀（即电铸）到硅母版上来制造阴模。然后，该负金属印模被用于封装小至20 nm的药丸转移特征的聚合物膜。压花特征将包括尺寸为100 μ m、5 μ m、500 nm和50 nm的特征层级。100人消费者可以用放大镜观察到微米的特征，在药店用光学显微镜观察到5微米的特征，在批发分销水平用SEM观察到500纳米的特征，在制造过程中用SEM或AFM观察到50纳米的尺度。印模无法复制，因为用于制造最小特征的技术的操作略低于其最佳分辨率范围，从而产生许多不可能复制的独特和随机缺陷。 本提案中开发的“LFAT”技术代表了一种系统，在该系统中，制造商、分销商或消费者可以对药品进行标记和检测。识别特征是不可能复制的，易于应用，无需FDA批准。这项技术可以迅速部署，以防止因消费假冒产品而造成的疾病和痛苦。

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.