BIO-NANO-CHIPS FOR ON-SITE DRUG SCREENING

• US 20140094391A1
• Filed: 03/21/2012
• Published: 04/03/2014
• Est. Priority Date: 05/12/2011
• Status: Active Grant

• Current Assignee: Rice University
• Original Assignee: Rice University
• Inventors: McDevitt, John T., Christodoulides, Nicolaos, Floriano, Pierre N., Simmons, Glennon
• Granted Patent: US 9,709,580 B2
• Time in Patent Office: Days
• US Class Current: 506/18
• CPC Class Codes: A61B 10/0051 for taking saliva or sputum samples devices for receiving spittle A61J9/00
• CPC Class Codes: A61B 10/007 for taking urine samples measuring urological functions A61B5/20; genital receptacles A61F5/451; urinals for bed-ridden persons A61G9/006
• CPC Class Codes: A61B 5/151 Devices specially adapted for taking samples of capillary blood, e.g. by lancets , needles or blades
• CPC Class Codes: A61B 50/30 Containers specially adapted for packaging, protecting, dispensing, collecting or disposing of surgical or diagnostic appliances or instruments for wound clamps A61B17/10; for ligaturing clips A61B17/122; packages or dispensers for surgical gloves or finger-stalls A61B42/40
• CPC Class Codes: A61F 13/36 Surgical swabs, e.g. for absorbency or packing body cavities during surgery A61F13/38 takes precedence
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: G01N 21/64 Fluorescence; Phosphorescence
• CPC Class Codes: G01N 33/946 CNS-stimulants, e.g. cocaine, amphetamines
• CPC Class Codes: G01N 33/948 Sedatives, e.g. cannabinoids, barbiturates opiates G01N33/9486
• CPC Class Codes: G01N 33/9486 Analgesics, e.g. opiates, aspirine

Abstract

A bio-nano-chip (BNC) technology that works in connection with non-invasive samples, such as saliva, cheek swab or urine samples that can be easily performed by non-specialists, such as security personnel and police officers is disclosed. The microfluidic system for drug testing includes an analyzer or reader having a housing containing a slot for receiving a cartridge, a drug testing cartridge, a processor having a user interface, an optical or energy sensing means, and a means for moving fluid.

Claims

1. A disposable drug testing cartridge comprising a generally flat substrate having thereon individual bead sensors arranged in an array, wherein each bead sensor is a porous polymeric bead having a drug bound thereto, wherein said drug is selected from three or more of tetrahydrocannabinol (THC), diazepam, oxazepan, nordiazepam, temazepam, D-amphetamine, methamphetamine, methadone, morphine, cocaine, 3,4-Methylenedioxyamphetamine (MDA) 3,4-Methylenedioxymethamphetamine (MDMA) and biological metabolites of same.

2. The disposable drug testing cartridge of claim 1, further comprising internal microfluidics on said substrate for carrying fluid to and from said bead sensors.

3. The disposable drug testing cartridge of claim 2, further comprising a sample entry port.

4. The disposable drug testing cartridge of claim 3, further comprising at least one reagent blister fluidly connected to said bead sensors.

5. The disposable drug testing cartridge of claim 4, further comprising at least one waste fluid chamber fluidly connected to and downstream of said bead sensors.

6. The disposable drug testing cartridge of claim 4, further comprising positive and negative control bead sensors and calibrator bead sensors.

7. The disposable drug testing cartridge of claim 4, wherein every drug bead sensor is present in said array in at least duplicate.

8. The disposable drug testing cartridge of claim 4, wherein every drug bead sensor is present in said array in at least triplicate.

9. The disposable drug testing cartridge of claim 4, wherein said drug is conjugated to said bead sensor via a linker.

10. The disposable drug testing cartridge of claim 4, wherein said bead sensor in stored in at least 25% glycerol.

11. The disposable drug testing cartridge of claim 4, wherein said bead sensor in stored in at least 30% glycerol.

12. A disposable drug testing cartridge comprising:

a. a generally flat substrate having embedded microfluidic channels connecting an inlet to an embedded downstream assay chamber containing a removable array of bead sensors and having a transparent cover over said assay chamber,

b. one or more reagent chambers fluidly connected to and upstream of said assay chamber; and

c. one or more waste fluid chambers fluidly connected to and downstream of said assay chamber;

d. wherein each bead sensor is a porous polymeric bead of size between 50-300 nm±

10% having a drug conjugated thereto, wherein said drug is selected from three or more of THC, diazepam, oxazepan, nordiazepam, temazepam, D-amphetamine, methamphetamine, methadone, morphine, cocaine, MDA and MDMA and biological metabolites of same.

13. The disposable drug testing cartridge of claim 12, wherein said bead sensor comprises crosslinked agarose.

14. The disposable drug testing cartridge of claim 12, wherein said bead sensor is conjugated to said drug via a linker.

15. The disposable drug testing cartridge of claim 12, wherein said bead sensor is conjugated to said drug via a peptide linker.

16. The disposable drug testing cartridge of claim 12, wherein one of said reagent chambers contains an absorbent pad containing dried antibodies for said drugs, each antibody conjugated to a fluorophore.

17. The disposable drug testing cartridge of claim 16, wherein at least one of said reagent chambers contains a wash buffer.

19. The system of claim 16, wherein said processor uses line profile and/or circular area of interest to analyze said data.

23. A kit comprising the cartridge of claim 12 wrapped in an airtight package, a vial of wash buffer, and a swab.

18. A lab-on-chip system for drug testing comprising:

a. a housing containing i) a slot for receiving a cartridge, ii) a processor having a user interface, iii) an optical or energy sensing means, and iv) a means for moving fluid;

b. a cartridge comprising a substrate having inlets and microfluidics for moving fluid and a plurality of individual bead sensors in an array, wherein each bead sensor is a porous polymeric bead having a drug bound thereto, wherein said drug is selected from three or more of THC, diazepam, oxazepan, nordiazepam, temazepam, D-amphetamine, methamphetamine, methadone, morphine, cocaine, MDA, MDMA and a biological metabolite of same;

c. wherein said cartridge fits into said slot such that said inlets are fluidly connected to said means for moving fluid;

d. wherein said optical sensing means is configured to receive a signal from said bead sensors;

e. wherein said microfluidics are configured to allow fluid movement past said bead sensors;

f. and wherein said processor and user interface control said lab on chip system and said processor records data from said optical sensing means.

20. A drug testing assay comprising:

a. a microfluidic lab-on-chip based reverse competitive immunoassay that uses a disposable cartridge and a separate reader, wherein said cartridge fits into a slot on said reader, and said reader performs said competitive immunoassay and outputs a result,

b. said cartridge comprising;

i. a generally flat substrate having embedded microfluidic channels connecting an inlet port to an embedded downstream assay chamber having a transparent cover and containing a removable array of bead sensors,

ii. one or more reagent chambers fluidly connected to and upstream of said assay chamber; and

iii. one or more waste fluid chambers fluidly connected to and downstream of said assay chamber;

iv. wherein each bead sensor is a porous polymeric bead of size between 50-300 nm±

10% having a drug conjugated thereto, wherein said drug is selected from three or more of THC, diazepam, oxazepan, nordiazepam, temazepam, D-amphetamine, methamphetamine, methadone, morphine, MDA, MDMA and biological metabolites of same;

c. wherein said reverse competitive immunoassay has a lower limit of detection for each of said drugs of <

10 ng/ml and a detection range of at least four orders of magnitude.

21. The drug testing assay of claim 20, said cartridge comprising 4 or more of said drugs.

22. The drug testing assay of claim 20, said cartridge comprising each of said drugs.

24. A sample collection and solubilization device, comprising

a. a container closed with a removable cap;

b. a lower portion of said container having a buffer separated from an upper portion of said container by a piercable membrane;

c. said cap comprising a flexible bulb passing through said cap and fluidly connected to a hollow stem ending in a point, a lower portion of said stem being coated with an absorbent or bristled material for collecting a biological sample,

d. wherein said device is proportioned to store said cap with said stem and said swab in said upper portion of said container, but can reach said buffer when said point pierces said piercable membrane, and said flexible bulb can be used to draw up and deliver said buffer.