MODULAR MICROFLUIDIC DEVICE FOR ANALYTICAL BIOASSAY

Abstract

Described is a modular microfluidic device (MMD) for producing an analytic composition from a biological fluid sample, said device comprising a reagent module (RM) comprising a reagent reservoir containing a reagent and an eluent reservoir containing an eluent, said reagent and eluent reservoirs being coupled to one or more RM microchannels; and a sample preparation module (SPM) comprising a SPM microchannel adapted to couple with the RM microchannel whereby fluid continuity between SPM and RM microchannels is produced on coupling, and: (i) a sample inlet for receiving said biological fluid sample; (ii) an outlet for delivering said analyte composition; (iii) a sensor component; (iv) a mixing chamber; (v) a metering chamber; (vi) an eluent chamber; (vii) a valve; and (viii) a solid phase extraction element (SPE); wherein said metering chamber is of fixed volume and shape and substantially ellipsoidal, the metering chamber having an inlet and an outlet, said inlet and/or outlet being in fluid communication with one or more microchannel(s) of the MMD.

Claims

1. A modular microfluidic device (MMD) for producing an analyte composition from a biological fluid sample, said device comprising: (a) a reagent module (RM) comprising a reagent reservoir containing a reagent and an eluent reservoir containing an eluent, said reagent and eluent reservoirs being coupled to one or more RM microchannels; and (b) a sample preparation module (SPM) comprising a SPM microchannel adapted to couple with the RM microchannel whereby fluid continuity between SPM and RM microchannels is produced on coupling, and: (i) a sample inlet for receiving said biological fluid sample; (ii) an outlet for delivering said analyte composition; (iii) a sensor component; (iv) a mixing chamber; (v) a metering chamber; (vi) an eluent chamber; (vii) a valve; and (viii) a solid phase extraction element (SPE); wherein said metering chamber is of fixed volume and shape and substantially ellipsoidal, the metering chamber having an inlet and an outlet, said inlet and/or outlet being in fluid communication with one or more microchannel(s) of the MMD.

2. The device of claim 1 wherein the metering chamber is spheroidal.

3. The device of claim 2 wherein the metering chamber is an oblate spheroid.

4. The device of claim 2 wherein the metering chamber is a prolate spheroid.

5. The device of claim 1 wherein the metering chamber comprises two axially opposed substantially frustoconical or substantially hemispherical portions.

6. The device of claim 5 wherein the two axially opposed substantially frustoconical or substantially hemispherical portions are separated by a substantially cylindrical portion.

7. The device of any one of claim 1 wherein the inlet and outlet of the metering chamber are axially opposed on: (a) the long axis of the metering chamber; or (b) the short axis of the metering chamber.

8. The device of claim 1 wherein the volume of said metering chamber is within the range: (a) 1 l to 1000 l; or (b) 10 l to 1000 l; or (c) 50 l to 500 l.

9-18. (canceled)

19. The device of claim 1 wherein said metering chamber is comprised within a solid, rotatable valve head located within the SPM, which valve head may be rotated to reconfigure the microchannel flow path through the metering chamber by changing the position of the inlet and/or outlet of the metering chamber relative to one or more ports in the SPM.

20-22. (canceled)

23. The device of claim 1 wherein said SPM further comprises an aspirator in fluid communication with the sample inlet of the SPM for withdrawing an aliquot of said biological fluid when contained in a sample vessel, said aspirator being operably coupled to a pneumatic fluid level sensor.

24-46. (canceled)

47. The device of claim 1 wherein the SPM further comprises a filter, optionally a plurality of one or more filters.

48. (canceled)

49. The device of claim 47 wherein the one or more filters are adapted to filter a biological fluid sample.

50. The device of claim 1 wherein said biological fluid is selected from: whole blood; lysed whole blood; serum; plasma; urine; sputum; sweat; follicular fluid; synovial fluid; amniotic fluid; a nasopharyngeal aspirate; a bronchial aspirate; semen and cerebrospinal fluid.

51-79. (canceled)

80. The device of claim 1 wherein said analyte is selected from a marker indicative of a drug selected from: alcohol, cocaine, marijuana, opiates, amphetamine, methamphetamine, amphetamines, phencyclidine, benzodiazepines, barbiturates, methadone, tricyclic antidepressants, heroin, steroids, niacin, xanax, vicodin, oxycontin, adderall, morphine and nicotine.

81. The device of claim 1 wherein said analyte is selected from: vitamin D; methylmalonic acid; an immunosuppressant; a steroid and an antimicrobial.

82-113. (canceled)

Description

EXEMPLIFICATION

[0196] Embodiments of the present invention will now be described by way of example with reference to the accompanying drawings in which:

[0197] FIG. 1 shows a perspective view of a CMMD according to the invention.

[0198] FIG. 2 illustrates schematically apparatus embodying the present invention.

[0199] FIG. 3 schematically illustrates a CMMD of the invention.

EXAMPLE 1

Microfluidic Device

[0200] Referring now to FIG. 1, the CMMD comprises a reagent module (RM) 2 comprising several reagent reservoirs 4 each containing a reagent (not shown) and an eluent reservoir 6 containing an eluent (not shown), said reagent and eluent reservoirs being coupled to RM microchannels 8 and a sample preparation module (SPM) 10 comprising a SPM microchannel (not shown) coupled with the RM microchannel whereby fluid continuity between SPM and RM microchannels is established. The SPM has a sample inlet 12 connected to an aspirator 16 for receiving a biological fluid sample contained in a sample vessel 18, an outlet for delivering analyte composition, a sensor component, a mixing chamber, an ellipsoidal metering chamber, an eluent chamber, a number of valves (not shown), a solid phase extraction elements (SPE) 20 and metering chamber valve head 21.

[0201] The CMMD is provided with several interface sites 22 for coupling with a processing head (not shown),

EXAMPLE 2

Microfluidic Platform

[0202] Referring now to FIG. 2, the apparatus comprises a platform 30 comprising a drum carousel 32 containing a plurality of stacked MMDs 33 and a conveyor 34 containing a chain of vessels 36 each containing a biological sample. A processing head 38 is coupled with an MMD 39 loaded from the carousel by automated robot (not shown), during which the RM and SPM modules are themselves also coupled to form a CMMD 40, while an individual sample vessel 42 is brought into registration with an aspirator on the CMMD (not shown).

EXAMPLE 3

Vitamin D Preparation Sequence

[0203] Referring now to FIG. 3, the dotted lines indicate the RM having seven reagent reservoirs A-G containing reagents as follows: [0204] A: Methanol (100 l) [0205] B: Standard (40 l)+methanol (500 l) [0206] C: Buffer (200 l) [0207] D: Methanol (100 l) [0208] E: Water (100 l) [0209] F: 70% methanol in water (100 l) [0210] G: Water (40 l)

[0211] The aspirator (not shown) is pushed through the rubber septum of a sealed vessel containing a sample of serum (not shown). The aspirator is lowered towards the surface of the serum sample while pulses of air at low pressure air are driven through it. A pressure transducer (not shown) measures back pressure and thereby permits monitoring of the approach of the aspirator to the surface of the serum sample.

[0212] Once the surface of the serum sample is detected, pulsing of low pressure air through the aspirator is terminated and the aspirator tip further lowered a predetermined distance beneath the surface of the serum. 200 l of serum is then drawn into sample inlet (50) along microchannel 51 into metering chamber 53 containing the ellipsoidal metering chamber 54 until determined to be full using sensor 55.

[0213] A valve head on the metering chamber (not shown) is then rotated by a rotating valve head actuator in a processing head (not shown) so that ports are aligned with microchannel 57. The serum is then pushed into the mixing chamber 56 along with the contents of reagent reservoirs B and C along microchannel 57 and their arrival and absence of entrained bubbles confirmed with sensor 58. The contents of the mixing chamber are then mixed with bead 60.

[0214] The SPE 63 with a two port rotating valve head 62 is then conditioned with: (a) the contents of reagent reservoir D along microchannel 66; then (b) the contents of reagent reservoir E along microchannel 68, the valve head 62 being rotated to bring the ports into alignment with the appropriate microchannels with a rotating valve head actuator in a processing head (not shown) with excess being collect in waste chamber 70.

[0215] 500 l of sample from the mixing chamber 56 is then loaded onto the SPE 63 along microchannel 64 with excess being collect in waste chamber 70. The SPE 63 is then washed with the contents of reservoir F along microchannel 74. SPE 63 is then dried with 250 l of air.

[0216] The analyte is then eluted from the SPE 63 into eluent chamber 76 with the contents of reservoir A along microchannel 78. Polarization of the analyte composition in the eluent chamber 76 is then improved by adding the contents of reservoir G along microchannel 80.

[0217] The polarized analyte composition is then injected into an LC-MS device (not shown) via outlet 82 for analysis.

Equivalents

[0218] The foregoing description details presently preferred embodiments of the present invention which are therefore to be considered in all respects as illustrative and not restrictive. Those skilled in the art will recognize, or be able to ascertain, using no more than routine experimentation, many equivalents, modifications and variations to the specific embodiments of the invention described specifically herein. Such equivalents, modifications and variations are intended to be (or are) encompassed in the scope of the following claims.