Assessment of a 60-Biomarker Health Surveillance Panel (HSP) on Whole Blood from Remote Sampling Devices by Targeted LC/MRM-MS and Discovery DIA-MS Analysis

Telehealth, accessing
healthcare and wellness remotely, should
be a cost-effective and efficient way for individuals to receive care.
The convenience of having a reliable remote collection device for
blood tests will facilitate access to precision medicine and healthcare.
Herein, we tested a 60-biomarker health surveillance panel (HSP),
containing 35 FDA/LDT assays and covering at least 14 pathological
states, on 8 healthy individuals’ ability to collect their
own capillary blood from a lancet finger prick and directly compared
it to the traditional phlebotomist venous blood and plasma collection
methods. All samples were spiked with 114 stable-isotope-labeled (SIL)
HSP peptides and quantitatively analyzed by liquid chromatography-multiple
reaction monitoring-mass spectrometry (LC/MRM-MS) scheduled method
targeting 466 transitions from 114 HSP peptides and by a discovery
data-independent acquisition mass spectrometry (DIA-MS) method. The
average peak area ratio (PAR) of the HSP quantifier peptide transitions
from all 8 volunteers’ capillary blood (n =
48), venous blood (n = 48), and matched plasma (n = 24) was <20% coefficients of variation (CV). Heat
map analysis of all 8 volunteers demonstrated that each individual
had a unique biosignature. Biological replicates from capillary blood
and venous blood clustered within each volunteer in k-means clustering analysis. Pearson statistical analysis of the three
biofluids indicated that there was >90% similarity. Discovery DIA-MS
analysis of the same samples using a plasma spectral library and a
pan-human spectral library identified 1121 and 4661 total proteins,
respectively. In addition, at least 122 FDA-approved biomarkers were
identified. DIA-MS analysis reproducibly quantitated (<30% CV)
∼600–700 proteins in capillary blood, ∼800 proteins
in venous blood, and ∼300–400 proteins in plasma, demonstrating
that an expansive biomarker panel is possible with current mass spectrometry
technology. Both targeted LC/MRM-MS and discovery DIA-MS analysis
of whole blood collected on remote sampling devices are viable options
for personal proteome biosignature stratification in precision medicine
and precision health.