Competitive volumetric bar-chart chip with real-time internal control for point-of-care diagnostics.
Point-of-care (POC) testing has become widely used in clinical analysis because of its speed and portability; however, POC tools, such as lateral flow assays, suffer from low specificity, unclear readouts, and susceptibility to environmental and user errors. Herein, we report an ELISA-based competitive volumetric bar-chart chip (CV-chip) that eliminates these limitations. The CV-chip displays the readout in the form of ink bar charts based on direct competition between gases generated by the sample and the internal control. By employing a "competition mode", this platform decreases the potential influence of background resulting from environmental factors and provides visually clear positive or negative results without the requirement of calibration. In addition, the on-chip comparison enables the device to distinguish imperceptible differences (less than 1.3-fold) in human chorionic gonadotropin (hCG) concentrations that are near the cutoff value for pregnancy (∼1.4 ng/mL). We also utilized the ELISA-based CV-chip to successfully detect biomarkers from cancer cells. As a proof-of-concept application in a clinical setting, the CV-chip was employed to evaluate the status of drugs of abuse in 18 patients. For six different drugs, zero false-positive and very few false-negative (<2%) results were reported in more than 100 tests. This new ELISA platform offers a clinical diagnostics tool that is portable and easy to use, and provides improved clarity and sensitivity due to the inclusion of a real-time internal control.
†Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, Texas 77030, United States.|‡Department of Cell and Developmental Biology, Weill Medical College of Cornell University, New York, New York 10065, United States.
Ying
Y
Li
§Department of Pathology and Genomic Medicine, Houston Methodist Hospital, 6670 Bertner Avenue, Houston, Texas 77030, United States.
Jie
J
Xuan
†Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, Texas 77030, United States.
Tom
T
Xia
†Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, Texas 77030, United States.|‡Department of Cell and Developmental Biology, Weill Medical College of Cornell University, New York, New York 10065, United States.
Xin
X
Han
†Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, Texas 77030, United States.|‡Department of Cell and Developmental Biology, Weill Medical College of Cornell University, New York, New York 10065, United States.
Yujun
Y
Song
§Department of Pathology and Genomic Medicine, Houston Methodist Hospital, 6670 Bertner Avenue, Houston, Texas 77030, United States.
Zheng
Z
Cao
∥Department of Geriatrics, The Second Clinical Medical College of Jinan University, Shenzhen, 518120, China.
Xin
X
Jiang
⊥Department of Neurology, The Second Clinical Medical College of Jinan University, Shenzhen, 518120, China.
Yi
Y
Guo
§Department of Pathology and Genomic Medicine, Houston Methodist Hospital, 6670 Bertner Avenue, Houston, Texas 77030, United States.
Ping
P
Wang
†Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, Texas 77030, United States.|‡Department of Cell and Developmental Biology, Weill Medical College of Cornell University, New York, New York 10065, United States.
Lidong
L
Qin
D014408:Biomarkers, Tumor / Q000032:analysis*; D045744:Cell Line, Tumor; D006063:Chorionic Gonadotropin / Q000032:analysis*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D013287:Illicit Drugs / Q000032:analysis*; D061986:MCF-7 Cells; D046210:Microfluidic Analytical Techniques; D019095:Point-of-Care Systems; D015813:Substance Abuse Detection; D013997:Time Factors
D014408:Biomarkers, Tumor; D006063:Chorionic Gonadotropin; D013287:Illicit Drugs