# US 7,743,928 B2 · Integrated apparatus and methods for treating liquids

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- Number: US 7,743,928 B2
- Document ID: US7743928B2
- Status: Granted
- Kind: B2
- Application number: 10/658,447
- Filed: 2003-09-08
- Published: 2004-07-08
- Granted: 2010-06-29
- Earliest claimed: 2002-09-07
- Inventors: Timothy Crowley; Vincent B. Pizziconi
- Web page: https://patentgrep.com/patent/US7743928B2

## CPC

- B01D 61/18: Apparatus therefor
- B01D 67/0058: {by selective elimination of components, e.g. by leaching}
- B01D 71/0213: {Silicon}
- B01L 3/502753: {characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation}
- B01L 2300/0681: Filter
- B01L 2300/0816: Cards, e.g. flat sample carriers usually with flow in two horizontal directions
- B01L 2400/0406: capillary forces
- G01N 21/01: Arrangements or apparatus for facilitating the optical investigation
- G01N 33/49: Blood {(chemical methods for determining blood cell populations G01N33/5094; chemical analysis of blood groups or blood types G01N33/80)}
- B01D: SEPARATION (separating solids from solids by wet methods B03B, B03D; by pneumatic jigs or tables B03B; by other dry methods B07; magnetic or electrostatic separation of solid materials from solid materials or fluids, separation by high-voltage electric fields B03C; centrifuges, vortex apparatus B04; presses per se for squeezing-out liquid from liquid-containing material B30B9/02; treatment of water C02F, e.g. softening by ion-exchange C02F1/42; {arrangements of air intake cleaners in gas turbine plants F02C7/05} ; arrangements or mounting of filters in air-conditioning, air-humidification or ventilation F24F13/28)
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

A passive self energized, liquid device operates entirely on capillary action. A microfilter fractionates nanoliter volumes of suspension such as whole blood into suspended particles or cells and liquid fractions. Blood, for example, is fractionated with minimal cell lysis, and the filtrate (plasma) flux is dependent upon design parameters similar to factors controlling blood filtration in microporous membranes, i.e. active filter area, fluid velocity and microfilter geometry. Weir-style filters communicate with a blood flow channel to separate plasma from blood moving by capillary action. An expanded downstream channel with multiple parallel capillary blood flow path provides continuing movement of blood past the filters. Lysing is controlled by the size of the filter pores and the duration of adherence of the red blood cells to the pores. The controlled lysis or prevention of lysis of red blood cells is accomplished by manipulating the significant capillary forces generated in the filters. Filtration, cell lysis and microchannel blood flow models are integrated into an overall microfilter design useful for fabricating microfilter devices for lab-on-a-chip clinical applications where they can be coupled with on-chip electrical and electro-optical devices.

## Claims

### Claim 1

An instrument for observation, treatment, or analysis of a sample of a liquid comprising:
a liquid input opening for receiving a liquid sample,
a first passage leading from said liquid input opening to an expanded liquid flow region,
at least one weir filter located tangentially along each side of said first passage between said liquid input opening and said expanded liquid flow region,
at least one filtrate channel located on each side of said first passage parallel to said first passage,
said at least one weir filter in communication with said first passage and said at least one filtrate channel located on the same side of said first passage as said at least one weir filter, and
said liquid flow expanded region comprising a plurality of parallel capillary channels sized to sustain a draw of said liquid sample through said first passage tangentially past said at least one weir filter by capillary action.

### Claim 2 (depends on 1)

The instrument according to claim 1, wherein said liquid sample is a complex fluid.

### Claim 3 (depends on 1)

The instrument according to claim 1, wherein said draw of said liquid sample through said first passage tangentially past said at least one weir filter by capillary action filters said liquid sample into at least one filtrate flow in said at least one filtrate channel and a remaining liquid sample flow in said first passage.

### Claim 4 (depends on 1)

The instrument according to claim 1, wherein said plurality of parallel capillary channels are sized to sustain a draw of said liquid sample through said first passage for a predetermined amount of time.

### Claim 5 (depends on 3)

The instrument according to claim 3, wherein said plurality of parallel capillary channels are sized to produce at least a nanoliter of said at least one filtrate flow from said at least one filter.

### Claim 6 (depends on 3)

The instrument according to claim 3, wherein said at least one filtrate channel further comprises a testing location in which at least a portion of said at least one filtrate flow is collected for analysis.

### Claim 7 (depends on 6)

The instrument according to claim 6, wherein the analysis of said at least one filtrate flow includes electro-optical analysis.

### Claim 8 (depends on 7)

The instrument according to claim 7, wherein said electro-optical analysis comprises a laser, a first reflective sidewall at said testing location positioned to direct laser light from the laser through said test location, a photodetector, and a second reflective sidewall at said testing location positioned to direct laser light from said test location to the photodetector.

### Claim 9 (depends on 2)

The instrument according to claim 2, wherein said complex fluid is a biological fluid.

### Claim 10 (depends on 9)

The instrument according to claim 9, wherein said biological fluid comprises at least one formed element.

### Claim 11 (depends on 10)

The instrument according to claim 10, wherein said at least one weir filter lyses at least a portion of said at least one formed element.

### Claim 12 (depends on 10)

The instrument according to claim 10, wherein said plurality of parallel capillary channels are sized to control the degree of lysing of said at least one formed element.

### Claim 13 (depends on 1)

The instrument according to claim 1, wherein each capillary channel of said plurality of parallel capillary channels are about 45 μm wide and at least 10 μm in length.

### Claim 14 (depends on 1)

The instrument according to claim 1, wherein said at least one weir filter comprises a channel having width of about 200 μm along the side of said first passage, a height of about 1 μn, and a length of about 30 μm coupling said first passage to said filtrate channel.

### Claim 15 (depends on 6)

The instrument according to claim 6, wherein said analysis comprises at least one of an identification of at least one analyte in said at least one filtrate flow, a quantification of the concentration of at least one analyte in said at least one filtrate flow, and an isolation of at least one analyte in said at least one filtrate flow.

### Claim 16 (depends on 15)

The instrument according to claim 15, wherein said at least one analyte in said at least one filtrate flow comprises at least one of a protein, an amino acid, an enzyme, an electrolyte, a nucleotide, and a dissolved gasses.

### Claim 17 (depends on 1)

The instrument according to claim 1, wherein said expanded liquid flow region comprises a total width from about 0.4 to 2.5 mm and a length of from about 2 to 20 mm.

### Claim 18 (depends on 1)

The instrument according to claim 1, wherein said a plurality of parallel capillary channels have a cross-sectional dimension a, where 0.3 μm>a>0.1 μn.

### Claim 19 (depends on 3)

The instrument according to claim 3, wherein said at least one filtrate flow comprises a plasma filtrate.