Despite rapid advances in diagnostic and imaging technologies, a method for noninvasive monitoring of the immune system does not exist. The standard white blood cell count (WBCC), a key clinical measure for assessing patients’ health, requires drawing blood, which poses inherent risks for secondary infection and anemia in vulnerable patient populations. In addition, the specialized equipment, expertise, and infrastructure are not always available in resource-poor settings. Here we present a method for noninvasive and label-free WBCC by imaging human oral mucosa with a miniaturized oblique back-illumination microscope (mOBM). In a pilot study involving 34 healthy subjects, we validated our system’s ability to detect and quantify circulating leukocytes and compared our image-based WBCC to standard laboratory measurements. The ability to perform noninvasive WBCC will enable real-time assessment of the immune status during infection and inflammation or in response to therapeutic intervention without repetitive blood sampling.

The authors have declared no competing interest.

This work is supported in part by DOD grants and by the Massachusetts General Hospital Executive Committee Fund for Medical Discovery and the SPIE Franz Hillenkamp Fellowship to A.B.

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The experimental protocols related to human volunteers were performed in accordance with the guidelines and regulations of Massachusetts General Hospital. The study protocol (2021P003047) was approved by the Internal Review Board (IRB) of Massachusetts General Hospital. Informed consent was obtained from all subjects participating in our study.

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The data that support the findings of this study are available from the corresponding author upon reasonable request.