Assays used in conjunction with a thermal contrast reader are disclosed. In the assay, the test strip includes materials that can develop a thermal response if a target analyte is present in a sample. The thermal contrast reader includes housing having an opening to receive the test strip at a test location, an energy source directed at the test location and a heat sensor directed at the test location. The heat sensor is configured to sense heating of the test strip upon activation of the heat source at the test location, if the target analyte is present in the sample. The heat sensor can provide sensor output using diagnostic circuitry coupled to the sensor output and configured to provide a diagnostic output. The diagnostic output can indicate the diagnostic condition of the patient as a function of the sensor output. The present disclosure also includes methods of detecting target analytes and kits comprising lateral flow assays and thermal contrast reader.