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.
We propose to produce a low-cost, reliable point-of-care and home-care neutrophil counting device that supports self-administered neutrophil testing by chemotherapy patients at home. Employing an innovative method to encode optical forward-scatter signals from individual white blood cells, this user-friendly microfluidic device holds promise to significantly reduce the risk of hospital infection and health care expenses. The proposed project aims at demonstrating the medical viability of the technology and commercializing the device.
|Zhang, Alex Ce; Gu, Yi; Han, Yuanyuan et al. (2016) Computational cell analysis for label-free detection of cell properties in a microfluidic laminar flow. Analyst 141:4142-50|