RESEARCH ARTICLE
Factors affecting sedimentational separation
of bacteria from blood
William G. Pitt
1
| Mahsa Alizadeh
1
| Rae Blanco
1
| Alex K. Hunter
1
|
Colin G. Bledsoe
1
| Daniel S. McClellan
1
| Madison E. Wood
2
| Ryan L. Wood
1
|
Tanner V. Ravsten
1
| Caroline L. Hickey
1
| William Cameron Beard
3
|
Jacob R. Stepan
3
| Alexandra Carter
1
| Ghaleb A. Husseini
4
| Richard A. Robison
2
|
Evelyn Welling
1
| Rebekah N. Torgesen
1
| Clifton M. Anderson
1
1
Chemical Engineering Department, Brigham
Young University, Provo, Utah
2
Department of Microbiology and Molecular
Biology, Brigham Young University,
Provo, Utah
3
Department of Chemistry and Biochemistry,
Brigham Young University, Provo, Utah
4
Chemical Engineering Department, American
University of Sharjah, Sharjah, United Arab
Emirates
Correspondence
William G. Pitt, Chemical Engineering
Department, Brigham Young University, 330W
Engineering Building, Provo, UT 84602.
Email: pitt@byu.edu
Funding information
National Institutes of Health, Grant/Award
Number: R01AI116989
Abstract
Rapid diagnosis of blood infections requires fast and efficient separation of bacteria from
blood. We have developed spinning hollow disks that separate bacteria from blood cells
via the differences in sedimentation velocities of these particles. Factors affecting sepa-
ration included the spinning speed and duration, and disk size. These factors were varied
in dozens of experiments for which the volume of separated plasma, and the concentra-
tion of bacteria and red blood cells (RBCs) in separated plasma were measured. Data
were correlated by a parameter of characteristic sedimentation length, which is the dis-
tance that an idealized RBC would travel during the entire spin. Results show that char-
acteristic sedimentation length of 20 to 25 mm produces an optimal separation and
collection of bacteria in plasma. This corresponds to spinning a 12-cm-diameter disk at
3,000 rpm for 13 s. Following the spin, a careful deceleration preserves the separation
of cells from plasma and provides a bacterial recovery of about 61 ± 5%.
KEYWORDS
bacterial bloodstream infection, bacterial separation, centrifugation, disk design, E. coli, human
blood, sedimentation
1 | INTRODUCTION
There is increasing need to rapidly identify the species and antibiotic
resistance profile of bacteria causing bloodstream infections (BSI) so
proper treatment commences quickly. Empirical applications of broad-
spectrum antibiotics often work satisfactorily, but the general use of
these agents may promote the development of resistant bacterial
strains.
1,2
Unfortunately, when undiagnosed BSIs of carbapenem-
resistant organisms produce a state of sepsis in a patient, the survival
rate decreases by 7.6% per hour of ineffective treatment,
3
eventually
producing a 50% mortality rate.
4,5
Thus rapid identification of species
and antibiotic resistance are essential.
Because the bacterial concentration in BSIs is extremely low
(often between 1 and 100 CFU/ml
6,7
), growth amplification is
required for most diagnostics.
8
While PCR and other genomic amplifi-
cation techniques are rapid and work well for the high concentrations
found in urine,
9-11
they are often ineffective in blood samples due to
interfering agents and degradative enzymes.
12
Our proposed diagnostic process described herein requires only 7 ml
of blood, a typical volume collected in vacutainer tubes. The challenge is
to rapidly separate a maximal amount of bacteria from ~5 × 10
9
red
blood cells (RBCs), ~5 × 10
6
white blood cells (WBCs) and ~3 × 10
8
platelets per ml of blood. Table 1 and Table S1 (Supporting Information)
tabulate some important characteristics of blood components.
Received: 14 January 2019 Revised: 19 June 2019 Accepted: 1 August 2019
DOI: 10.1002/btpr.2892
Biotechnology Progress. 2019;e2829. wileyonlinelibrary.com/journal/btpr © 2019 American Institute of Chemical Engineers 1 of 9
https://doi.org/10.1002/btpr.2892