Microfluidic neutrophil counter for at-home use by chemotherapy patients

描述（由申请人提供）：本提案描述了一种快速计数患者血液样本中中性粒细胞的新方法。中性粒细胞减少症是化疗的常见副作用，其特征是中性粒细胞数量异常低，而中性粒细胞是抵抗感染的主要防御手段。如果不及时就医，中性粒细胞减少症可能会危及生命。由于大多数肿瘤患者（美国每年约有100万）是在门诊接受治疗的，因此必须密切和频繁地监测中性粒细胞的数量，以便在发生中性粒细胞减少症和相关感染时及时治疗。此外，接受抗增殖性化疗伴中性粒细胞减少症的患者对医院感染特别敏感，每年造成99,000人死亡。因此，考虑到癌症患者的利益，以及我们医疗保健系统的成本和效率，在患者住所进行自我给药中性粒细胞检测的能力尤为重要和有吸引力。今天的全血细胞计数设备是为中央医疗设施设计的。它们非常昂贵，而且病人操作起来太复杂。即使是简单的即时血液检测设备也是为医生办公室设计的，不适合病人在家进行检测。为了解决这一重要的未满足需求，我们提出了一种独特的创新设备，用于患者在家中进行中性粒细胞检测。我们的中性粒细胞计数装置利用了细胞特性，特别是当流过微流体通道时。最近的研究表明，由于基本的流体动力学特性，细胞尺寸和可变形性的组合信息可以确定流动细胞在微流控通道中的平衡位置。我们发明了一种空时编码技术，对每个行进小区的前向散射信号进行编码。通过解码信号，我们以非常高的精度（0.1 μ m）获得每个细胞的速度和位置。自细胞位置内

DESCRIPTION (provided by applicant): This proposal describes a novel method for rapidly counting neutrophils in a patient's blood sample. Neutropenia, characterized by an abnormally low number of neutrophils that serve as the primary defense against infections, is a common side effect of chemotherapy. Without prompt medical attention, the condition of neutropenia may become life threatening. Since the majority of oncology patients (about 1 million each year in the US) are treated on an outpatient basis, the number of neutrophils must be closely and frequently monitored to allow timely treatment in the event of neutropenia and associated infections. Furthermore, patients undergoing antiproliferative chemotherapy with neutropenia are particularly sensitive to nosocomial (hospital) infections, causing 99,000 deaths each year. Therefore, in consideration of the interest of cancer patients, as well as the cost and efficiency of our healthcare system, the ability for self-administered neutrophil test at the patient's residence is particularly important and attractive. Today's complete blood count devices have been designed for central medical facilities. They are very expensive and too complicated to operate by patients. Even the simper blood test devices for point-of-care applications are designed for use in physician's office and unsuitable for patient-administered testing at home. To address this important unmet need, we propose a unique and innovative device for patient-administered neutrophil testing at home. Our neutrophil counting device takes advantage of cellular properties manifested specifically when flowing through microfluidic channels. Supported by recent publications, the combined information of cell size and deformability can determine the equilibrium positions of flowing cells in a microfluidic channel due to fundamental fluidic dynamic properties. We invented a space-time coding technique to encode the forward scattering signal of each travelling cell. By decoding the signal, we obtain the velocity and position of each individual cell with a very high accuracy (0.1 um). Since the cell position within a microfluidic channel is directly related to the cell volume and deformability, we have found an innovative method to classify white blood cells, particularly neutrophils. Our device and analysis method possesses the following salient features: (1) it is minimally invasive, requiring only 5 microliters of blood (a similar amount to a typical blood glucose test); (2) straightforward sample preparation and test procedures that can be performed by persons without medical training; (3) accurate test results that are easy to understand and compliant to medical standards; (4) low cost; and (5) high portability. We therefore envision that the successful development and commercialization of the device will bring tremendous benefits to cancer patients because the device can greatly reduce the risk of hospital infection, cut down healthcare costs, improve outcomes during chemotherapy due to close monitoring of neutropenia, and minimize the inconvenience and pain for unnecessary hospital and emergency room visits.