Bioenergetic profiling of circulating blood cells and systems, devices, and methods relating thereto

A method of determining increased morbidity in a subject, the method comprising the steps of:

• (a) providing a blood sample obtained from the subject, wherein the subject is a human of at least 50 years of age;
• (b) isolating circulating blood cells from the blood sample;
• (c) distributing the isolated circulating blood cells into an analytical vessel;
• and,
• (d) measuring respiratory capacity of the isolated circulating blood cells, wherein the measuring the respiratory capacity of the isolated circulating blood cells comprises measuring Maximum Oxygen Consumption Rate (Max OCR) and Spare Respiratory Capacity (SRC) of the circulating blood cells, wherein SRC is a difference between Max OCR and Basal Oxygen Consumption Rate (Basal OCR) of the circulating blood cells, and wherein the measuring the respiratory capacity of the isolated circulating blood cells comprises the steps of:
• (I) measuring a first rate of oxygen disappearance from a medium to determine Basal OCR;
• (II) adding an ATP synthase inhibitor to the medium;
• (III) adding a mitochondrial uncoupler to the medium;
• and,
• (IV) measuring a second rate of oxygen disappearance from the medium to determine Max OCR;
• wherein the subject has increased morbidity compared to a reference population, if at least one of (i), (ii), or (iii) is measured in step (d):
• (i) Max OCR of less than about 250 pmol/min/500,000 cells,
• (ii) SRC of less than about 100 pmol/min/500,000 cells, or
• (iii) SRC of 40% or less of Max OCR,
• and wherein the reference population is a population in same age group as the subject and comprises one or both of
• subjects with same type of ailment, disease, or disorder as the subject, or
• subjects without the same type of the ailment, the disease, or the disorder as the subject.