Journal of Membrane Science 219 (2003) 15–25
Optimum dialysis membrane for endotoxin blocking
Masayo Hayama
a
, Takehiro Miyasaka
b
, Seiichi Mochizuki
c
, Hiroko Asahara
b
,
Ken-ichiro Yamamoto
a
, Fukashi Kohori
a
, Katsuhiko Tsujioka
b
, Kiyotaka Sakai
a,*
a
Department of Chemical Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan
b
Department of Physiology, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan
c
Department of Medical Engineering, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan
Received 30 August 2002; received in revised form 23 January 2003; accepted 2 February 2003
Abstract
We have reported a novel method of visualizing endotoxin (Et) distribution inside an Et-blocking filtration membrane
using both fluorescence-labeled Et and a confocal laser scanning fluorescence microscope (CLSFM) in our previous paper [J.
Membr. Sci. 210 (2002) 45]. The objective of the present study is to clarify Et-blocking mechanism of dialysis membranes. Six
kinds of dialysis membranes with varying materials (hydrophilic and hydrophobic) and varying structures (pore diameter, skin
layer location and thickness, and water content) were evaluated by CLSFM together with other techniques such as atomic force
microscopy (AFM). Physicochemical property of a membrane material affects Et-adsorbing efficiency, and further membrane
structure affects Et-plugging efficiency. Rejected Et distribution in the membranes with varying materials and structures is
successfully visualized using fluorescence-labeled Et by CLSFM. Et adsorption on the membranes occurs first, followed by
the narrowing of their pores, and afterward pore plugging is continued. Adsorption plays a vital role in Et-blocking. Double
skin layer structure is valid for preventing of Et contamination than only inner skin layer structure because the double skin
layer structure blocks Et more farther from blood-side surfaces than the only inner skin layer structure.
© 2003 Elsevier Science B.V. All rights reserved.
Keywords: Endotoxin; Hemodialysis; Highly permeable dialysis membranes; Confocal laser scanning fluorescence microscopy; Atomic force
microscopy
1. Introduction
Since the finding of
2
-microglobulin (M
W
: 11,800)
as a causal substance in the carpal tunnel syndrome of
chronic hemodialysis patients,
2
-microglobulin has
been removed using highly permeable dialysis mem-
branes having larger pores [2–4]. Such large-pore
membranes allow endotoxin (Et), harmful substances
contained in the dialysate, to enter the blood [5–7].
*
Corresponding author. Tel.: +81-3-5286-3216;
fax: +81-3-3209-7957.
E-mail address: kisakai@waseda.jp (K. Sakai).
Therefore, high functional dialysis membranes are
strongly desired to be developed with contradictory
performance, high Et-blocking efficiency and high
diffusive permeability. Moreover, a greatly sterile
dialysate is needed. Various kinds of Et-blocking fil-
tration membranes are presently used to remove Et
from the dialysate [8–13]. Et-blocking filtration mem-
branes should be further improved so that they stand
long use and have excellent Et-blocking efficiency on
high flux conditions.
In solutions, Et is present as a dimer, a configuration
like a sandwich with hydrophilic polysaccharide part
outside and hydrophobic lipid A part inside. They form
0376-7388/$ – see front matter © 2003 Elsevier Science B.V. All rights reserved.
doi:10.1016/S0376-7388(03)00131-5